376 PATHOLOGY 6. ERRORS OF BLOOD-MAKIXG ix MATURE LIFE. The words quoted above from Sir William Jenncr " Whatever depresses the mother s powers of forming good blood tends to produce rickets in an offspring" are a special application of a general doctrine of blood-making which has been held empirically by the medical profession at all times. It is not easy to discover with scientific pre cision the facts of blood-making in mature life upon which this doctrine, otherwise amply justified, is based. It is remarked by Sir Thomas Watson : " Although we cannot doubt that any considerable modification or defect of the fluids that feed and renovate the blood, and particularly of the chyle, must have a direct influence upon its com position and quality, we really know but little about them except in their effects. We seldom have any means of procuring these the first products of nutrition so as to ex-, amine them, or to test their qualities, yet we can perceive causes that are likely to deteriorate or deprave those fluids (unfit aliment, impure air), and we know that, under the continued operation of such causes, the blood, replenished by these fluids, is actually and sensibly modified." The more recent development of the physiology of metabolism has been followed by an extension of our knowledge of the state of the blood in disease ; thus the text-books speak of such conditions as glycaemia (glucose in the blood), aceton- asmia, cholremia (jaundice), lipaamia (fat in the blood), uraemia, tfcc., some of which fall to be spoken of in sec tions following. In the presenf section it is rather the corpuscular part of the blood that has to be considered with reference to its renewals in mature life. It is now known that red blood-disks are continually being added to the blood, continually perishing in a like ratio ; the red marrow of bone is unquestionably a source of the red disks, and so probably is the pulp of the spleen ; again, the liver plays some part, not yet precisely determined, in the cycle of changes that the solid elements of the blood undergo. Confining the attention, then, to the corpuscular elements of the blood, we shall best approach the question from the side of the colourless or white blood-corpuscles, the undue proportion of which is the most obvious fact in the import ant disease called leukaemia. Leuk- Leukasmia, or Lcucocythasmia. The relation of the colourless semia, corpuscles of the blood to the red disks is variously explained ; all that we know, however, from such occasional cases as blood-cysts points to the red blood -disks being the detached protoplasm of the haematoblast, the nucleus surviving. Appearances in the sub cutaneous tissue of the foetus, in the thymus, in the spleen, and in bone-marrow point in the same direction. The colourless corpuscles of the blood would thus be the surviving nuclei of the original hrematoblasts, the red disks being detached portions of the proto plasm of the same. There would be in any case several red disks for one surviving nucleus ; but in actual blood the proportion of cells of the latter kind is very much smaller than that. The pro portion varies in health from time to time, and it is usually increased during pregnancy, making a physiological leucocytosis. Ordinarily the colourless corpuscles are in the proportion of from 1 in 300 red (after a meal) to 1 in 1000 red (in the fasting state). If the colourless cells are the surviving nuclei of haemato- blasts, we must suppose that the protoplasm continues to be renewed around the old nucleus, so that the same htematoblast gives off successive generations of red disks. The cells of red marrow, of the thymus (while it lasts), and of the splenic pulp would thus be standing sources of new red corpuscles. Evi dences that they are so are not wanting in fine sections of these tissues, although the process of budding of the hfemoglobin- Difonnit&s du Systems, osseux, Paris, 1839-43; Humphry, The JIvmnn Skeleton, Catnb., 1853 ; various authors in Trans. Path. Soc., vol. xxxii., Lond., 1881. Of osteomalacia : Kassowitz, op. cit., chap. vi.; Cohnheim, Varies, uber allgem. Patholorjie, vol. i. p. 513; Pub- bert, in Virchoio s Archiv, vol. Ixxx. Of cretinism (morbid anatomy): Virchow, several papers reprinted in his Oes. Abhandl, p. 891 sq., Frankfort, 1856 ; Eberth, Diefoetale Rachitis und ihre Rrziehungen zum Cretinismm, Leipsic, 1878 ; Barlow and others in Trans. Path. Soc., Loud., 1881-84. Of chlorosis: Virchow, Ueberdie C/ilorose, &c., Berlin, 1872 ; Laache, Die A ndmie, Christiania, 1883. Of hemophilia : J. Wickham Legg, Treatise on Haemophilia, Lond., 1872. tinted fragments of protoplasm is not so marked in all its stages as in those abnormal instances of haematoblastie activity to which reference has been made (blood-cysts, angeioma of liver). In the normal process there seems to be less cleavage of the nucleus, although the nucleus is not unfrequently seen to be constricted or half - divided ; the marginal protoplasm detaches itself from one side as if with little trouble, new protoplasm gathers around the nucleus, and so the supply is kept up just as if it were secretion from the cells of a gland. If the cell which had disengaged its red dish protoplasm in the form of one or more disks or globules were thereupon to continue in its nuclear state, and to acquire no further investment of cell -substance, it would practically amount to a, colourless corpuscle of the blood. There are, as we have seen, always a few such cells in the blood one in several hundred red disks and the real difficulty about them is to understand why they should be present in the circulating fluid at all. In the disease of leucocythaemia they increase enormously, so as to be in the ratio of twenty, fifty, or even one hundred to the hundred red disks, which are themselves absolutely fewer ; and, if we interpret that pheno menon according to the view that they are residual nuclei of hrematoblasts, we shall conclude that the hasmatoblasts have veiy generally ceased to produce new generations of red disks, have stood still at the lower grade, and have passed bodily from their blood-forming habitat into the blood-stream. There would be, in short, an arrest of function, manifesting itself not only in the great falling off in the number of red disks but also in the presence within the vessels of these sluggish or crippled elements of the blood-making organs and tissues, as if in lieu of the red disks themselves. What, then, is the actual condition of the proper seats of blood-making in the leucocy thsemie disease 1 The interest centres in the state of the spleen and of the bone- Moi marrow ; according to modern views the so-called lymphatic leuco- anal y cythaemia belongs to another class of processes and may be here of 1< - disregarded. The spleen is in all cases enlarged, from twice up a-mi to fifty times its normal size ; it retains its form, but its struc ture is firmer, less sanguineous, streaked with pale or yellowish lines, or mottled with yellowish patches. The marrow in the bones is often changed in appearance : it has become grey or red dish grey and diffluent ; and this change may be observed even in the marrow-fat of long bones. These changes are essentially in the haematoblastic tissue, in the splenic pulp and in the bone- marrow ; the cells of that tissue have to a great extent ceased to form blood, their activity has taken another and formative direc tion, from which no functional product results (red blood-disks), but mere overgrowth of tissue and of cellular nuclei. The haana- toblasts have, in fact, become constructive when they should have continued functional. The enormous number of colour less corpuscles thrown into the blood has to be traced to the same diversion of the haematoblastic forces which has in the spleen led to textural overgrowth ; instead of remaining in the seats of blood-making, and continually reclothing themselves uith haemoglobin -tinted protoplasm, the haematoblasts have passed bodily into the blood -current in their naked nuclear condition. The colourless cells of leukaemia may be said to have the same relation to the haematoblastic process that was claimed, in a former section (see p. 365), for the pus-cells of granulations. The peculiar state of the bone-marrow characteristic of leukaemia has often been compared to granulation-tissue ; in some cases it has even the appear ance of puriform infiltration. Again, the first cases of leucocy thannia were described by Hughes Bennett as cases of "suppuration of the blood" ; and, if the pus of granulations is an analogy for the cells of leukremic blood, the textural developments of granulations may be held to be an analogy for those formative changes in the spleen which are found in its enlarged state. Pscudo-lf,uk(emia. Leucocy thaemia is a definite and generally fatal disease wherein the increase of colourless corpuscles of the blood and the decrease of the red disks are referable, in the last resort, to disordered hrematoblastic function in the spleen or bone- marrow, or in both. There may be a state of Icucocytosis without Leu this profound and fatal haematoblastic disorder, wherein the in- cyt< . crease of colourless corpuscles is referable to organs and tissues which have no blood-making function. Affections of the lymph atic glands are the principal occasion of this leucocytosis or pseudo-leukaemia, and such affections may occur in the course of morbid processes so various as scrofula, cancer, and typhoid fever. A considerable degree of leucocytosis occurs also in the later months of pregnancy as a perfectly normal incident. The lymph atic glands and the lymphatic follicles of the mucous mem branes are collections of lymphoid cells which have no true blood-making^ function, however closely their cells may resemble those of the bone-marrow, of the spleen -pulp, and of the thymv.s ; they are rather related to the cellular by-products, or the solid waste of secretion (see section 7). From them, or through them, the colourless cells in the blood may receive considerable additions from time to time ; but these have a significance quite different from the profound disturbance of blood-making which constitutes leucocytlutmia, and they are better classed under the heading of
