Pathology

PATHOLOGY(πάθος, λόγος, the doctrine of disease or (lit.) of that which is suffered) holds a peculiar place among the natural sciences. Although it is laid down, in the opening sentences of the Hippocratic treatise De prisca medicina, that the medical art, on which all men are dependent, should not be made subject to the influence of any hypothesis (such as that of the four cardinal qualities, hot, cold, moist, and dry), that the care and cure of the sick should not be subordinated to pathological theory, but should be guided by experience; yet the practitioners of medicine have at no time been able to dispense with theory, not even those avowed followers of the Hippocratic tradition who, while they professed a kind of quietism amidst the rise and fall of systems, have none the less been profoundly influenced by theory at every step of their practice. The position of Cullen is the only rational one: “You will not find it possible to separate practice from theory altogether; and, therefore, if you have a mind to begin with theory, I have no objection. . . . To render it safe, it is necessary to cultivate theory to its full extent P

§ 1.— Progress and Scope.

The progress of pathology hitherto has been exactly parallel with the progress of philosophy itself, system succeeding system in genetic order. No other department of biological science has shown itself so little able to shake off the philosophical character, or to run in the career of positivism or pure phenomenalism. This unique position of pathology among the natural sciences is doubtless owing to the fact that it is a theory of practice, a body of truth and guess-work existing for the benefit of a working profession which is daily brought face to face with emergencies and is constantly reminded of the need of a reasoned rule of conduct. It is idle to attribute the philosophizing habit in medicine, or the habit of system-making, to an unscientific method in past times. The extremely various points of view from which the problems of diseased life are approached in the very latest and most authoritative writings are an evidence that the difficulty is really inherent in the subject-matter.

The positive progress of the biological sciences does not essentially depend on the philosophical conception of life as action and reaction; but the notion of action and reaction comes to the front in every page of a pathological treatise, and at every step of practice. In considering the forms of diseased life, if not in the study of living things themselves, we. are constantly driven back to that ultimate analysis. The influences from without, which make up aetiology or the doctrine of causes of disease, assume a position in medicine the urgency or immediate interest of which far exceeds that of the biological problem, “the correspondence between life and its circumstances.” The standing difficulty in pathology has been its relation to aetiology, or the relation of the ens morbi to the agens morbi. One of the most singular ways of meeting the difficulty is that of Paracelsus, who boldly perpetrated the paradox: “Ens ist ein Ursprung, welches Gewalt hat, den Leib zu regiren.” The five classes of entia of Paracelsus are a composite catalogue, of which (l)j (2), and (5) stand for influences from without, and (3) and (4) for spontaneities, dispositions, or liabilities within. From time to time the centre of interest has been shifted to within the body, as in the “animism” of Stahl, in the “vitalism” of the school of Montpellier (end of 18th century), and in the “cellular pathology” of Virchow. A discussion of the inherent difficulty of holding the balance fair between that which is “exopathic” in disease and that which is “endopathic” may be read in Virchow’s article, “Krankheitswesen und Krankheitsursachen,” written in reply to objections that the cellular pathology was inadequate. “What I wished to treat of in the Cellular Pathology,” he says, “was the behaviour of the elements of the living body in the usual kinds of illness, or, to put it more briefly, the history of the elementary processes of disease. Upon that basis, it seemed to me, the doctrine of the nature of disease should be built. The respective causes I adverted to only now and then; thus I spoke of poisons, and even fungi had a place in the cellular pathology, although a very modest one. If the Cellular Pathology had ever pretended to be a general pathology it would have contained also the whole of aetiology.” Thus far Professor Virchow writing in 1880. If we now turn to a text-book of the same date, which does bear the title of General Pathology, that of Professor Cohnheim, we find pathology defined as “an explanatory science which seeks (1) to discover the causes of disease, and (2) to ascertain the esoteric connexion subsisting among disease-manifestations.” It is only (2) that forms the subject of Professor Cohnheim’s two volumes; aetiology, he remarks, is absolutely without limits. It “comes into relation with” cosmical physics, meteorology, geology, sociology, chemistry, botany, and zoology; from these sciences it gets its subject-matter. In the general pathology of Cohnheim, accordingly, aetiology is omitted; and with it are omitted many of the problems underlying the philosophical systems of the past, which have “only an historical interest,” as well as much of the natural history of disease. General pathology, he says, knows no other direction and no other order than physiology, “and accordingly we shall take up successively, and in the same order as physiology would take them, the pathology of the circulation, digestion, respiration, tissue-nutrition, and the like” (the pathology of the nervous system is not included in the two volumes). Without adducing other instances of eclecticism in the contents of modern pathological text-books, it will be convenient to give a brief notice of the latest attempt at a philosophical scheme of diseases,—the Elemente der Pathologie of Rindfleisch, 1883.

There are certain groups of symptoms, says Rindfleisch, which recur with the uniformity of a type in the most various diseases, depending as they do upon one constant factor,—the human body and its structural and functional tendencies. The larger number of maladies do not arise autochthonously or “under a whole skin,” they are generated by certain morbific causes; and it is the variety of causes that corresponds to the variety of disease-species, or to those ever-changing sequences and coexistences of symptoms in which the experienced eye of the practitioner learns to distinguish one disease from another. The morbific cause is an invasion upon the normal course of our life, usually a strong and forcible interference with the physical and chemical constitution of a particular part of the body. The disease as a whole stands for the effects of this interference, and these effects flow in part from the nature of the morbific cause and in part from the nature of the body which suffers. That which is uniform in these effects flows from the nature of the sick body; that which is various flows from the variety of morbific causes. It is above all the seat of the disease, its duration, the sequence and combinations of the type-groups of symptoms which are determined by the morbific cause. Only this varying element can be used to distinguish one disease from another. Therefore there is only one truly natural principle of subdividing diseases and only one point of view in special pathology from which the construction of a natural system may be approached,—namely, the aetiological principle of classification and the aetiological system. In each group of diseases, and in each individual disease, the causation has to be inquired into as closely as possible and described after the natural-history manner; we have to ask how and where the cause acts upon the organism, and finally to show how, from this action and from the reaction of the organism towards the same, we may explain those special features of disease and that special morbid process which are peculiar to each group of maladies or to each malady individually. In a word, the species morbi are made by the morbific causes; all that separates one disease from another is contained in the cause; only the causal differences, and no other, furnish those units of disease-life which can be brought under genera and species.

If we now inquire into the categories of causation, according to Rindfleisch, we find that they are five in number, as were the categories of Paracelsus. They are (1) injury from without, (2) parasitism, (3) deficient rudiments and defective growth, (4) over-exertion, and (5) premature involution or obsolescence. It is impossible not to discover heterogeneous elements in this enumeration; it is a composite catalogue like that of Paracelsus, and we shall find it hard to say in the case of (3) and (5) whether we are dealing with the ens morbi or with the agens morbi.

A statement of the definition and scope of pathology similar to that of Rindfleisch had been given by John Simon in his Lectures on General Pathology. Diseases were for the most part the normal phenomena of life under abnormal circumstances. “When you know the whole case you are obliged to admit that, according to the normal constitution of the body, the symptoms in question ought to have followed the operation of those several causes.” The doctrine of disease, accordingly, is mostly an “exopathic” one, although a small residue of it may be “autopathic.” It is impossible, says Simon, absolutely to exclude autopathic diseased states; there may be some such, mostly developmental, which “are actual caprices and spontaneities of life, without any exterior causation whatsoever.”

The exopathic point of view may be said to be the dominant one at present; more particularly, it is from the aetiological side that the enormous aggregate of contagious and infective sickness is mostly studied. Thus in the nosology of Rindfleisch the whole of the specific fevers and infections (including even climatic fevers) are placed (tentatively) under the head of “Parasitism,” the parasites being minute living organisms having their independent place in the scale of being. The numerous researches of the parasitic school may be regarded as the most formal attempt as yet made to separate the study of the agens morbi from that of the ens morbi. 1

§ 2.— Introduction.

The plan of this article will be to take diseases as they occur in the concrete, and to apply an analytical method to them. In a given disease, or in an individual case of the same, the object would be to find the point of divergence from the beaten path of health, or, failing that, to seek out the nearest analogies in the physiological life for the unaccustomed and even grotesque things of disease. The effects of disease in man’s body may be likened, in a too pleasing figure, to the effects of a magician’s wand; there is

“nothing of him but is changed into something rich and strange.” This fascinating region of science is well outlined by Buckle in his remarks on the genius of Hunter :—

“In nature, nothing is really irregular or disorderly; if we are apt to fancy that the chain is broken, it is only because we cannot sec every link in it. . . . Being satisfied that everything which happens in the material world is so connected and bound up with its antecedents as to be the inevitable result of what had previously occurred, Hunter looked with a true philosophical eye at the strangest and most capricious shapes. To him they were neither strange nor capricious. They were deviations from the natural course; but it was a fundamental tenet of his philosophy that nature, even in the midst of her deviations, still retains her regularity.”

Hunter’s own words are: “Nature is always uniform in her operations, and, when she deviates, is still regular in her deviations. . . . It certainly may be laid down as one of the principles or laws of nature to deviate under certain circumstances.” The interest of this science, says Buckle, “depends simply on the fact that, when it is completed, it will explain the aberrations of the whole organic world.” The same science of deviations was provided for by Bacon in his classification of the sciences; and, after him, by D’Alembert, under the head of “Prodigies, or deviations from the usual course of nature,” in his classification for the Encyclopédie.

The science of deviations begins, in the writings of Hunter and of Paget, λvith the erratic forms of crystals, and with the indwelling power of crystals to repair injuries on the lines of their growth if they be placed in the proper mother-liquor. In the hands of each of these two pathologists this science next proceeds to elemental aberrations in the life of plants, where there is neither heart nor nervous system to complicate matters; and, so advancing from the simpler to the more complex, we should have a science of the abnormal coextensive with life itself. Without attempting to treat of pathology in that evolutional order, which proceeds from elemental pathology upwards, we may still adopt, for the narrower subject of human pathology, a somewhat analogous order, that is to say, a method based upon the facts of embryonic development. Confining our attention, then, to the processes of disease within the human body, and seeking out from among these the broadest of the facts, we shall find evidence, as we proceed, that the life of the body retains vividly the memories of its past. Nothing marks so generally the disease-incidents of life as crudity or recrudescence in the activities of cells, tissues, organs, and mechanisms. In other words, we shall find much in pathology to show that, when the organism goes wrong, it retreats to broader ground, or reverts to modes of life which it had come through. But, even in the normal functional and structural processes of the mature body, we find occasional evidences of the same reversion to embryonic modes of life. These are practically limited, in health, to the reproductive system, or to that part of life which goes to the maintenance of the species. Here we find periodicity still in full force, the same periodicity, primarily following the seasons, which underlies the life of plants and of most animals. The greatest example in the human body is the building up anew, from time to time, of an entire organ, the placenta, for the intra-uterine nourishment of the child; in this periodical formation we have a reversion, in the midst of mature life, to vessel-making and blood-making such as the body goes through otherwise only during its development. The provision for the nourishment of the child after it is born is a somewhat modified instance of the same kind. The full structure and function of the breast also develop periodically (although the framework is permanent), and each of these periodical developments is a repetition of the incidents in the original embryonic development of structure and function.

1 Literature. — Häser, Lehrbuch der Geschichte der Medicin und der epidemischen Krankheiten, 3d ed., 3 vols., Jena, 1875-82; Virchow, “Krankh ei ts wesen und Krankheitsursachen,” in Virchow's Archiv, vol. lxxix., 1880; Cohnheim, Vorlesungen über allgemeine Pathologie, 2 vols., Berlin, 1877-80; Rindfleisch, Die Elemente der Pathologie, ein natürlicher Grundriss der wissenschaftlichen Medicin, Leipsic, 1883; Siinon, Lectures on General Pathology, London, 1850.

It is when we come to the several tissues that we meet with the most striking reminders of persisting developmental characters, the most universal fact of the kind being the indwelling embryonic character of the common binding tissue. In that tissue, indeed, we have a constant reminder that in the midst of the very highest or most perfected modes of cellular life we are but a step removed from the most rudimentary. Thus in the brain and in the retina the elaborate nervous mechanism is supported on a framework of connective tissue; there is a morbid condition of these organs, called glioma, in which the connective tissue, or neuroglia, absolutely usurps the place of the nervous mechanism of which it is ordinarily the mechanical support; and this it may so completely do, as in disease of the pons Varolii, that even the outward form and markings of the part are not interfered with. An equally striking instance of a return to embryonic characters and predominance may sometimes be observed in the primitive nuclei of muscle; the muscle-fibres will be found to have surrendered their high function, to have retraced the steps of their development, and to have sunk their identity in a rudimentary form of cell-life.

Thus the body nowhere loses altogether the memory of the past, even when the periods of development and growth are, strictly speaking, ended. Among the normal processes of mature life there are such as amount to a recrudescence of structure and function; and an analogous recrudescence in the tissues is one of the most fundamental facts in the processes of disease. There are several advantages in proceeding in an exposition of pathological principles from this evolutional or developmental basis. It enables us to take up, in an order not unsuited to their importance, the sections relating to repair, to new growth of tumours, to errors of growth, such as rickets, to errors of blood-making, and the like. At the outset comes the process of repair, for which Paget has formulated the embryological principle as follows: “The powers for development from the embryo are identical with those exercised for the restoration from injuries; in other words, the powers are the same by which perfection is first achieved, and by which, when lost, it is recovered.”

§ 3.— The Process of Repair.

The spontaneity of certain polyps under injury is a good example of the indwelling power of all the cells and tissues to return to the established order, to the order and harmony which had been slowly acquired, and of which the memory is vividly retained. Trembley cut a hydra longitudinally, and “in an hour or less,” says Paget, “each half had rolled itself and seamed up its cut edges so as to be a perfect hydra. He split them into four; he quartered them; he cut them into as many pieces as he could; and nearly every piece became a perfect hydra. He slit one into seven pieces, leaving them all connected by the tail, and the hydra became seven-headed, and he saw all the heads eating at the same time. He cut off the seven heads and, hydra-like, they sprang forth again.” The recovery of perfection may be more gradual. Thus, Sir J. G. Dalyell (as quoted by the same writer) cut a specimen of Hydra tuba in halves; each half regained the perfect form, but only very slowly, and, as it were, by a gradual improvement of parts that were at first ill formed. In Tubularia indivisa, after the natural fall of its head, the stem was slit for a short distance down; an imperfect head was first produced, at right angles to the stem, from one portion of the cleft; “after its fall another and more nearly perfect one was regenerated, and, as it grew, improved yet more. A third appeared, and then a fourth, which was yet more nearly perfect, though the stem was thick and the tentacula imperfect. The cleft was almost healed, and now a fifth head was formed, quite perfect; and after it, as perfectly, a sixth and a seventh head. All these were produced in fifteen months.” This spontaneity resides in every living thing, and its efforts are directed by the memory of what the species had come through in reaching its place in the scale of organization; it is able, indeed, to make perfect reparation for injuries or losses only where the cells are little differentiated into tissues, or where the tissues are little specialized for diverse functions. In all animals, and most notably in the higher, this spontaneity is most effective for repair in the periods of development and growth. With reference to the degree of reparative power possessed, Paget formulates the rule as follows: “The amount of reparative power is in an inverse ratio to that of the development, or change of structure and mode of life, through which the anima! has passed in its attainment of perfection, or on its way thitherward.”

Healing by Granulations.— It will now be convenient to advance in medias res, and to give some account of the process of repair in man, where there is a breach of continuity in the course of the blood-carrying and lymph-carrying vessels, of the nerves, sinews, binding tissue, bone, fat, and skin. What is the effort that they each and all make to adapt themselves to the circumstances, in the case, let us say, of a stump after amputation? (The repair between the two ends of a broken bone will be discussed separately.) Disregarding the cases where the most perfect coaptation of parts is secured by the surgeon, and selecting the extreme case where the wound is “left to granulate,” the following is the order of events. The divided vessels being sealed up either by ligature or by clots of blood (which are in the end absorbed), there oozes from the raw surface a blood-tinged serous-looking fluid. Becoming paler by degrees, it sets on the surface as a greyish-white film or glazing, especially on the exposed surface of muscle. The film of surfaceglazing will be found to contain numerous corpuscles embedded in it resembling the colourless corpuscles of the blood. They have probably the same formative or reparative value as the granulationcells proper, but it will appear from the facts about to be given that they are practically superseded by the latter in all cases where a wound is “left to granulate.” After an interval of two or three days of apparent rest reddish points are seen on the edges of skin, on the muscular substance, and on the marrow of the bone; these are the beginnings of the granulation-tissue, which in the end covers the whole surface and grows until it fills up the gap somewhat beyond the level of the edges of skin. When the growth of granulations projects considerably beyond the skin it is known as “proud flesh.” Usually the surface begins to skin over when the defect of substance has been sufficiently made good, the new skin showing as a delicate bluish border or frill to the old skin. This frill becomes broader and broader until the growing points meet in the centre, and the continuity of the skin is restored. Meanwhile the granulation-tissue beneath has been changing into more characteristic forms of mature tissue, although the status quo antea is never quite restored.

Notwithstanding the regularity of this process, and its daily occurrence in surgical practice, there is an almost incredible amount of conflicting opinion as to its details,—radical differences as to the source or sources of the reparative material, and as to the mode of development of the new blood-vessels and of the new skin; and these differences of opinion must be the measure of the difficulty of analysis where the interference takes place in the highly complex and subtly integrated life of man. Direct observation of the reparative process does not of itself suffice to discover the law of it; it is necessary to seek elucidation from the nearest analogies, both among the regular processes of life and growth and among the deviations therefrom. Among the former there is in particular one rich source of analogous detail to be found in the periodical new formation on the surface of the uterus for the purposes of the embryo—in the placenta; among the latter are certain kinds of tumours and cysts. Hunter sought for a parallel to the new vessels of granulation-tissue in the first formation of vessels in the embryo; but these arise in the continuity of development, and not as a somewhat abrupt incident in the mature life. On the other hand, the formative process of the placenta is an example—and a unique example—of an extensive new growth of vascular tissue occurring periodically in the adult, and as somewhat of an interruption on the ordinary course of life. It matters little for this parallelism whether we accept the extreme position of Ercolani, that a total destruction of the uterine mucosa precedes the placental new growth, or whether we adopt the more likely view that the new formation takes place under an intact surface. In either case we have to do with a remarkable spontaneity of the body, a spontaneity which reveals the indwelling power of the tissues, and especially the vessel-making power.

Analogy of Placental new Formations.— The first adaptations for the placenta are not in the pre-existing vessels, but in the preexisting tissues around. The elongated and almost fibre-like cells become more plump, they join to form cylinders of nucleated protoplasm, the adjoining cylinders open out to form meshes between them, and all this takes place in the intervals between the vessels and their capillaries (fig. 1). The cells of the tissue return to that embryonic state which preceded the formation of blood-vessels, supplying their own juices, as it were, and opening out so as to form plasmatic canals in their midst. In the placental rudiment it is a mucus-like albuminous fluid that they mostly yield, but there is some evidence that they also yield blood-corpuscles. Meanwhile, the same process of enlargement has been taking place in the cells immediately surrounding the blood-vessels; and at a later stage it is the perivascular cells that keep up this actvity(fig. 2). The phase of development in which the cells supply their own juices, retaining them in meshes of the tissue, is succeeded by a new formation of vesseis, a more permanent provision. Certain tracts of cells are told off to form the walls of blood-vessels, the channel of the vessel being the space between two such adjoining tracts (fig. 3). These selected cylinders of cells become the new and enlarged system of blood-vessels, adequate to the requirements of the part. In this placental process the original capillaries play a very subordinate part; the thin cell-plates that form their walls are far outran in the hyperplastic race by the cells of the tissues around, and it is the latter which furnish the materials for the new vessels. That which distinguishes the placental new formation is the enormous thickness of the walls of the new vessels and their terminal capillary loops. It remains to consider whether this placental new formation of vascular tissue—the only instance of the kind in the ordinary course of adult life—offers any help to the understanding of granulation-tissue.

Tendon in a Granulating Stump.— It is at once evident that the tissues of a stump,after amputation have a very unequal value for formative purposes, and probably all of them a lower· value than the uterine tissue, which is at no time far removed from embryonic characters. This inequality is seen in the order in which granulations appear—first on the vascular layer of the skin, on the ends of muscle, and on the marrow of bone, and last on the ends of tendon. The attempt of a severed tendon to cover itself with a cap of granulations is somewhat feeble, and its slowness gives us an opportunity of marking points of detail. Tendon consists of wavy bundles of fibres in close order, and in full-grown animals its cellular elements are reduced to small dimensions. They are thin plates folded round the bundles, presenting in the face view the appearance in α, fig. 4, and in the side view the appearance in b, fig. 4. In the granulating end of a tendon the appearance is that of c, fig. 4; the thin plates have become solid or cubical, and where they have increased in number at the free end of the tendon they have lost their orderly arrangement; they have, in fact, become granulation-cells. The tendon has drawn upon its reserve of cells and placed them at the disposal of the reparative process. All the other tissues of the part have already done the same, some much earlier and more extensively than others. Wherever capillaries are most numerous there the cellular activity is greatest, the cells nearest to the wall of the capillary becoming more plump or more embryonic. The cellular material for the purposes of repair is supplied first around the severed vessels (according to some it is even supplied from within the vessels in the form of colourless bloodcorpuscles) of the highly vascular muscle, of the marrow of bone, and of the subcutaneous tissue, and ultimately even by the ends of the tendons. In the placental process the formative materials had been furnished much more evenly over the whole area.

Blood-vessels of Repair. — The next step is towards the nutrition of the formative cells. Whether their nutrition is for a time plasmatic (as in fig. 1, from the placental growth) does not appear; about the third day the formative tissue begins to be furnished with numerous bloodvessels. Their formation is very difficult to observe in young granulations; in older granulationtissue they have the appearance drawn in fig. 5, a series of parallel tubes making straight for the surface, ramifying on the same, joining by numerous loops near the surface, and of unequal calibre throughout their course, being widest on or near the surface.

These vessels are different in several respects from the vessels in a vascular area of the normal organism of corresponding extent, unless it be in the decidua uterina. They are not branching arterioles ending in a fine capillary network, but they are of somewhat uniform and exceedingly simple structure throughout, and their calibre is often gr eater at the distal than at the proximal end. We have next to consider how these vessels have originated.

The youngest granulations that can be prepared for examination consist of a uniform mass of cells, mostly round, and of somewhat wide vascular channels separated from the mass of cells by thin walls of more elongated cells (fig. 6). The most probable analogy for these new and wide vessels is not the embryo nor the tadpole’s tail, but the placenta; that is to say, certain of the cells along predetermined lines agminate to form the opposite sides of a tube, becoming adapted in shape to that end (fig. 3). According to Billroth, there is hardly ever in granulations an extension of the pre-existing capillaries by outgrowth of branching cells from their walls such as may be observed in the tadpole's tail (Untersuchungen über die Entwickelung der Blutgefässe, Berlin, 1856, p. 30); and the circumstances are so little analogous in the two cases that this statement may be readily credited. How the new vessels join on to the old is not easily made out, whether in the placenta or in granulations.

As the granulations get older, the vessels acquire a considerable longitudinal coat of spindle-cells. The individual granulation-points on the surface become fused into a more uniform fleshy stratum, the lower layers contract as the cells approximate to fibrous tissue, and skin begins to form on the surface. If a healed surface be examined long after, in microscopic sections through the skin and subjacent tissue, the parallel vessels will still be observed running at intervals towards the surface, only more obliquely than in the granulation-tissue. They are invested by a certain quantity of fibrous tissue arranged parallel to their course, while all the rest of the space between two of them is occupied by horizontal lines of fibrous tissue, with spindle-shaped cells lying regularly among the bundles. This change has been, first of spherical granulation - cells into spindle-shaped cells, with development of intercellular or perinuclear substance (fig. 7), and then fibrillation of the latter. It is worthy of note that a development into clastic fibres goes on in the scar for months or even years after healing is complete. Hairs, hair - follicles, and sebaceous glands are not reproduced in the skin of scars, nor are sweat-glands. On the other hand, fat develops readily in the usual situations.

Suppuration in Repair.— Meanwhile there has been a remarkable concomitant of the growth and adaptation of the reparative material, namely, a flow of pus or matter from the surface. Matter or pus varies in its physical characters somewhat; it may be creamy and yellowish-white (pus laudabile) or greenish-white, or it may be thin and watery or more viscid. It has an alkaline reaction and a faintly sweetish odour. Standing in a vessel, it separates into two parts,—a supernatant fluid or serosity, clear, and of a yellowish tint, and a sediment of pus-cells. The serum coagulates when boiled, and it may even happen that a fibrinous clot forms in pus after death, just as in drawn blood. The serum of pus contains from 1 to 4 per cent, of albumen, and very much the same salts as blood-serum. The cells of pus are spherical elements of somewhat uniform size, of the greyish colour of protoplasm, granular on the surface, and disclosing the presence of two, three, or four nuclei when treated with acetic acid (fig. 8). They are capable of amoeboid movements, and they may be seen to take into their substance such particles as charcoal with which the wound may be dressed.

Physiological Analogy of Pus.— Pus is a very remarkable adjunct of the reparative process—to go no farther into the inflammatory processes for the present. The pus-cells are evidently a condition or product of the granulation - cells on the extremities and sides of the vascular outgrowths, and they are detached from these situations, carrying with them a certain amount of fluid. Is there anything analogous to this in other formative processes of the body? The following analogy is very close in some at least of the circumstances. The interior of a cyst removed by operation from the neck region is found to be covered with vascular tufts, which have precisely the character of granulations as regards the blood-vessels. Each vascular· tuft is covered by a cap of cells like a granulation, and the same investment of cells can be followed as a cylindrical column down the vessel into the depth of the cyst-wall. These cells are somewhat peculiar. They are cubical or polyhedric elements, with a nucleus and a broad zone of protoplasm (fig. 9, a). On the summit and sides of a vascular tuft they are found becoming detached and disintegrated, the nucleus being cleft into fragments, which afterwards coalesce, while the cell-substance flows off in the form of spherical or oval or pear-shaped vesicles of a reddish tint (fig. 9, b). The cyst is a blood-cyst,—its contents, a clear brownish fluid with many red blood-disks floating in it, having been produced by the disintegration of the cells covering the vascular tufts. The cells are haematoblasts; their cell-substance is disengaged in drops which afterwards become red blood-disks, and their nucleus, after being cleft into several fragments of unequal size, is remade and survives as a cell of the size of a pus-cell, and containing several nuclei like a pus-cell (fig. 9, c). This is a curious instance of blood-making from connective-tissue cells late in life, and it is not so much inexplicable in its characters as it is rare in its occurrence. The formation of pus on the granulations of repair is one of the commonest of incidents, but it is open to elucidation even by a rare analogy. In the one case a blood-like fluid is formed, and in the other pus; the fluid part of pus corresponds to the plasma together with the red blood-disks in the cyst, and the cellular part of pus, the pus-corpuscle, corresponds to the surviving but broken-up nucleus of the haematoblast. The granulation-cell is comparable to the perivascular cell of this blood-making process, and in passing into the condition of a pus-cell with several small nuclei it disengages merely a fluid plasma and no red blood-disks. The cells of the injured part having returned to an embryonic state, their first activity is a revival of early embryonic activity; if they do not make blood, they yield that which may be regarded as its substitute, namely, pus.

This analogy will appear all the closer from a consideration of another cyst. In this new growth, which occurred under the skin of the back, and was removed, like the former, by operation, the Avail is lined by a certain thickness of tissue which is practically the same as the granulation-tissue of repair; there are the same parallel vessels ending in loops, the same cells, and the same deliquescence of the surface. The fluid in the cyst is indeed the result of this liquefaction—a somewhat turbid brownish fluid. In a small recess of the cyst there is a formation of a considerable layer of epidermislike scales on the surface. One important point of difference is that the deeper layers of cells show no tendency to become spindle-shaped, to take a transverse order in the intervals between the parallel vessels, and so to become fibrous tissue. On the contrary, one finds in the depths of the tissue the stems of vessels surrounded by zones of young cells, perivascular sources of the new growth by which the loss of substance around the terminal loops of the vessels is constantly made good. On these terminal loops the process is not one of pus-formation, nor is it altogether one of blood-formation as in the former cyst; but it is an intermediate process which helps us still further to understand the significance of the pus in repair. The new formation is comparable to that of the blood-cyst in the obvious perivascular grouping of its cells, and it is comparable to the granulations of repair in the forms of its cells; and it thus supplies the link between the blood-yielding tufts of the former and the pus-yielding vascular points of the latter. What, then, is the nature of the deliquescence in the interior of this cyst? It is partly blood; and there may be seen also the large cells from whose protoplasm the blood-disks have been derived. There are also seen the remarkable cells with nucleus cleft into three or four, so like the cells of pus (fig. 10, b); the latter are the surviving nucleus of the haematoblast, the peculiar form of which is best explained by watching the more perfect process of blood - formation on the wall of the blood - cyst. Fewer of the cells in the second cyst undergo this transformation; fewer of them ever attain the perfect form of haematoblasts so as to be able to undergo it. For the most part they pursue a devious development, and it is in this that they resemble granulation-cells. The difference is only one of degree; the type or law of the process is the haematoblastic type, which may be more or less perfectly attained. We are accordingly confirmed in the impression that pus-cells are the surviving nuclei of embryonic cells whose perfect law is blood-making, and that the fluid which accompanies them is the cell-protoplasm which has failed to disengage itself in the form of individual buds that easily pass into red blood-disks, but has become a veritable albuminous fluid. Pus, then, may be said to be blood absolutely wanting in red blood-disks, and with the colourless corpuscles in enormously disproportionate numbers. We shall afterwards see that there is a kind of blood—leucocythaemic blood—which approximates to pus in these its essential characters.

That which distinguishes the process of repair from the formative process in the two cysts, and in all tumours whatsoever, is that the former is self-limited; after a time skin forms on the surface of the granulations, and the lower layers of cells pass into the resting condition of fibrous tissue. Each of these adaptations has now to be described.

Formation of Skin on a Granulating Surface.— The new skin appears as a delicate bluish frill extending gradually over the raw surface from the margin of the old skin. Nothing is more natural, therefore, than to suppose that it is a continuous growth from the cells of the rete mucosum of the old skin; and, according to the embryological dogma of an impassable gulf between the epiblast, mesoblast, and hypoblast for histogenetic purposes, the new epidermis can have no other source than proliferation from corresponding cells of the old. But, dogma apart, there is a radical difference of opinion as to the origin of the epidermic or epithelial cells on the surface of granulations. Notwithstanding the fact that the new epithelium springs up alongside the old, it has appeared to many observers with the microscope that it was derived, not from subdivision of the latter, but from the granulationcells becoming flat and otherwise adapted to surface purposes. In considering these difficulties let us, as before, seek analogies among other formative incidents of mature life. In the first place it should be mentioned that the new skin may be peculiar. The accompanying figure (fig. 11) is drawn from a section through the scar of an ulcer of the leg which had broken out and healed repeatedly. The peculiarity is that the epithelial cells are everywhere a narrow belt which bends down and encloses the terminal vessels as in a loop; in other words, the surface vessels are driven through the midst of the rete mucosum of the new skin. For an analogy to this epitheliation of granulation-tissue we may take the case of the cyst already referred to; it was covered in part with a thick layer of epidermic scales. The origin of these in the cyst is not difficult to trace; they are the granulation-cells enlarged, with two, three, or four nuclei, and with a more homogeneous protoplasm. The surface-layer is in fact largely made up of multinuclear blocks, some of which become excavated in their interior, while their nucleated periphery forms a narrow belt of surfacecells with a descending loop enclosing a space, in which collections of blood-corpuscles may sometimes be seen (fig. 12). If we imagine the plexus of vessels ramifying on the granulating surface to form communications with these excavations in the multinuclear blocks, we should be able to understand how it is that they are driven through the rete mucosum of a scar, as in fig. 11.

Giant-cells in Repair.— These multinuclear blocks are the so-called giant-cells. Their occurrence in fungous granulations was described by Billroth {op. cit., p. 32) in 1856, he having previously seen them in the granulations of bone and taken them-to be elements “necessary for the new formation of vessels in osteophytes or in callus.” The accompanying figure (fig. 13) shows several examples of them from the granulations of a slow-healing stump. Precisely the same forms occur in the wall of the cyst whose structure has been already referred to in order to illustrate the granulations of repair.

But for these multinuclear blocks of tissue we have a clear physiological parallel in that unfailing source of analogies for the formative processes of mature life, namely, the placenta. The accompanying examples (fig. 14) are drawn from the deepest layer of a discoid placenta (the guinea-pig’s). Here it is evident that they result from the subdivision of a single nucleus within a growing cell of the inner muscular coat; and their place in the placental process is as clear as their histogenesis. They enter into the formation of the blood-sinuses of the deeper parts of the organ, sometimes forming a considerable part of the wall of a vessel by being excavated in their interior (the nuclei being driven to the side), at other times forming one side of a blood-channel,— a corresponding multinuclear block forming the other, and the lumen of the vessel being the space between them. They represent a somewhat feebler continuation of those vaso-fonnative processes in the placenta which we have already used as the analogy for the production of the new vessels of granulations. That their function and significance in granulations is not wholly vaso-formative will appear from the fact of their co - operating to build up the surface epithelium.

Conversion of Granulation-tissue into Scar-tissue.— The skin of a scar is never perfect; it is always thin, wanting the descending processes and papillae of the natural skin, and wanting also the hair-follicles, hairs, sebaceous glands, and sweat-glands. Its blood-vessels never become the orderly capillary loops of the original type; they remain for a time as an extensive plexus of large vessels close to the surface, giving a recent scar its livid appearance; afterwards the channels of the vessels become narrower, and many of them quite occluded; and the scar has in the end a somewhat blanched appearance, which continues even when the surrounding skin is thrown into a state of ruddy glow. The underlying tissue, however, gradually acquires more of the natural type. If a section be made through an old scar it will be seen that the subcutaneous tissue is fibrillar and fibrous, with more or less of fat-cells. In the figure (fig. 15), drawn from a section through the scar of an ulcer of the leg which had broken out and healed more than once, the tissue is composed of parallel wavy fibres, with spindle - cells between them at regular intervals, the cells having (as a characteristic of scar-tissue after repeated healing) brown pigment-grains in their substance. The successive changes which have led up to this horizontal fibrillation are not difficult to follow. While the ascending vessels acquire more and more of elongated cells on their walls, the granulation-cells in the intervals between them become extended horizontally or obliquely (see fig. 7), the spindle - cells among the fibrillar bundles in the figure being the surviving representatives of them. The change of the spherical cells into spindle-cells, which precedes the fibrillation, takes place first in the deepest or oldest stratum of the granulation-tissue, and it appears to be accompanied by a certain dragging doιvn or obliquity of the vessels running to the surface. There is always a considerable thickness of spindle - cells parallel to the vessels, so that these, together with the horizontal tracts between the vessels, make up a kind of warp and woof. But as the scartissue matures the horizontal bands come to overshadow the vertical or oblique. The fibrillation takes place, as it does in ordinary growth, in an intercellular or perinuclear homogeneous protoplasm, which becomes more extensive as the embryonic or purely cellular character of the granulation-tissue fades. One of the most striking facts in this development of embryonic tissue into mature tissue in the adult is its shrinkage, corresponding to the well-known contraction of the area of a healing surface.

Repair of a Broken Bone.— The reparative process in bone is much simpler and it may be said to be much easier than in the healing of a stump. The bones retain even to old age the materials out of λvhich new bone may be produced; these are the somewhat embryonic membrane covering the bone, or the periosteum, and the marrow. During’ the growing period these two tissues retain pronounced embryonic characters, and at all times they take on a formative action readily. However unlikely an object, then, a bone may seem for repair, it has within and around it the materials for a tolerably direct renewal of osseous substance. The most orderly or intelligible form of the reparative process is that seen in animals. A long bone, such as the tibia or shin-bone, after having been broken and carefully set, presents an appearance such as is drawn in the figure (fig. 16, a). Opposite the line of fracture there is a fusiform thickening all round the bone, which is bulky and cartilaginous for a time, and afterwards becomes greatly reduced in extent, and, at the same time, osseous in its structure. It is called the callus. It will be convenient to describe the details of this process of repair from actual specimens of the tibia of a young frog which was found undergoing repair after fracture. The tibia, when cleared of the muscles, was found to have a spindle-like enlargement about its middle of the size and shape of an oat (fig. 16, δ) and of a whitish colour. It was easily cut up into sections passing through its whole length as well as through the projecting ends of the spindle representing the normal shaft of the bone (fig. 17). The bulk of this fusiform enlargement is made up of cartilage developed between the upraised periosteum and the dense substance of the bone. But there is another and independent new-formed mass projecting from the canal of the bone, and clearly marked off from the wide extent of cartilage around it, —this is the direct osseous formation from the marrow. The cartilage has been produced from the periosteum, each spindlecell of the latter altering its form and developing a disproportionate amount of cell-substance, which becomes the hyaline matrix of the cartilage, while the nucleus of the original cell, generally excavated or reduced to a crescentic shape, remains as the cartilage-cell. From this cartilage, again, bone is formed very much as it is formed from thecentralrod of cartilage in the faetal bone, and it also resembles the latter in being formed only to be reabsorbed. In these preparations from the frog, narrow spiculae of bone may be seen starting from the thin end of the spindle and spreading over the surface of the cartilaginous callus. In the deeper strata of the latter, and still at the thin end of the spindle, the cartilage - cells group themselves round the walls of alveolar spaces, as in the ossification of epiphysial cartilage, and that is. doubtless the process which extends throughout the whole mass of cartilage. Meanwhile there has arisen a fungus-like protrusion of new bone from the medullary canal of the bone; it lines the inner walls of the medullary cavity for a short distance up from the line of fracture, and projects for a greater distance into the midst of the cartilaginous callus. This centre of ossification is intimately connected with the blood-vessels of the marrow; they form the framework of the osseous growth, the embryonic marrow-cells (themselves the lineal descendants of cartilage-cells) becoming the osteoblasts or future bone - corpuscles. The whole of the new growth of bone is ultimately moulded into a more compact form; but the seat of an old fracture will always retain a certain roughness of exterior, and a certain want of regularity in its Haversian systems.

The repair of bone in man is not altogether the same as in animals; the ensheathing cartilage is not usually found except in broken ribs, and the uniting osseous substance corresponds mostly to that part of the new bone (in the preparation from the frog) which issues from the medullary cavity in association with the blood-vessels of the marrow. The callus in man is accordingly said to be chiefly “intermediate” or between the broken ends, and partly also “interior,” or extending into the medullary canal; and it is naturally permanent and not subject to removal like the “ensheathing” callus developed from cartilage. But the sources of new bone in man depend upon the amount of displacement of the broken ends; if the displacement be very considerable, the connective tissues around may be drawn upon for bone-forming materials, their cells becoming embryonic in form and ultimately osteoblasts. Comparing the repair of a bone with the repair of soft parts, the former is much more direct; the osteoblastic tendency or memory is strong in the tissues within and around a bone, above all in the periosteum and in the young or red marrow; and true osseous union is readily effected except in such fractures as the neck of the thigh-bone and the knee-cap, where the union is often merely ligamentous or fibrous. In the “greenstick” fractures of children the periosteum is still a succulent layer engaged in the natural growth of the bones, and there is reason to suppose that it is the chief source of whatever reparative materials may be needed.

Repair of Nerves and Muscles.— When a nerve, such as the ulnar, is divided by a cut near the wrist, sensibility is lost over the area of skin to which the nerve is distributed, and, under ordinary circumstances, it is restored in about three weeks. The severed ends of the nerve are joined by a band of tissue, which has been proved, by examination of it at various stages of the reparative process in animals to be at first composed of embryonic spindle-cells arranged in the line of the nerve-bundles (fig. 18); these cells are derived from the nuclei of the neurilemma, they pass through the original embryonic phases, and ultimately become more or less perfect nerve-tubes filling the gap in the divided nerve,—a gap which may be a quarter or half an inch in length. In muscle, also, a corresponding process is described; but the repair of a ruptured muscle such as the rectus extensor of the thigh is commonly fibrous only, and the gap can be felt even through the skin.

§ 4.— Errors of Embryological Growth in certain Tissues—Mesoblastic Tumours.

No chapter or section treating of tumours as a whole can be homogeneous; and, in order to preserve the developmental or evolutional order already sketched, it will be convenient to consider here only a part of the morbid processes which result in tumours, leaving the rest to be introduced at appropriate points in the sequel. The disadvantage of applying the developmental or embryological idea to all tumours whatsoever comes out in the tumourhypothesis of Cohnheim. According to that hypothesis, the tumours of the body are due to the awakened growth of small centres or foci of embryonic tissue which had remained over from the faetal development, persisting in their embryonic characters while all else around them had assumed the characters of maturity. For the arguments and illustrations of this hypothesis the reader may refer to the section beginning at p. 622, vol. i., of Cohnheim’s Vorlesungen uber allgemeine Pathologie. It must suffice to say here that groups of resting embryonic cells in the various organs and parts of the body, or embryonic rudiments in the sense of Cohnheim, are not known to exist at all generally. That which we are well assured of is an indwelling power of all the mesoblastic tissues to revert to embryonic characters,—the spontaneity of the tissues never quite worn out, or the memory of development more or less deeply rooted in them to the end of life. From this point of view we have traced the process of repair, finding a developmental analogy even for pus. From the same point of view we have now to consider certain kinds of new formation as arising, not to make good defects, but under an erratic impulse, or in the course of an erratic spontaneity. Congenital tumours have always been regarded as errors of development, and it will be convenient to select a simple congenital tumour to begin with.

Fibroma. — The texture drawn in the figure (fig. 19) occurred in a tumour of the back of the neck in a young child having been there since birth. It is a fibroma, and consists essentially of bundles of wavy fibres crossing or decussating in direction, sometimes thick bundles, sometimes only a few strands, . the whole forming a dense warp-and-woof texture. The peculiarity is that such a tissue should have formed under the skin as a tumour or lump the size of a hen’s egg ; spread out in thin layers, the same warp-and-woof texture of fibres occurs naturally in the aponeuroses and the sheaths of muscles, and in other fibrous membranes, such as the dura mater; and the large number of nuclei among the fibres, as shown in the figure, would be appropriate to the fibrous tissue at the early period of life to which the tumour belonged. At various centres these embryonic cells had developed into fat-cells, so that the tumour may be called a fibro-lipoma. The tissue has increased in three dimensions, and so has resulted in a palpably distinct object in the body, which could be dissected out from among the surrounding structures as an individual thing. The overgrowth had taken place probably in one of the aponeuroses of the trapezius muscle, and the noteworthy point is that it has faithfully adhered to the warp-and-woof texture proper to the tissue on which it is based. The new formation possesses length, breadth, and thickness, and its fibres are interwoven in the three dimensions as if it had been constructed at some unusual kind of loom. The same interlacing of bundles of wavy fibres is found very commonly in the fibromata,—their favourite seats, besides the flat fibrous sheaths, aponeuroses, and membranes, being the uterus and its appendages, where the tumours may be stalked or sessile. Sometimes the fibres are concentrically arranged round a number of centres, or the bundles may pursue a sinuous course.

One variety may be specially mentioned as exemplifying a modification of fibrous structure which is often met with in various normal and pathological processes. In this modification the fibres become as if fused into broader homogeneous bundles, the nuclei being left lying as if in spaces or holes in a structureless ground-substance. This variety of fibroma is generally found in the bones of the jaws; it may be ossified at some points, the nuclei becoming the bone-corpuscles, and the homogeneous groundsubstance becoming impregnated with the earthy substance of bone. The accompanying figure (fig. 20) is drawn from a preparation of a fibrous tumour, ossified in part, within the medullary space of the lower jaw in an adult. It had been removed once, and grew again (recurrent fibroma or fibroid).

Where the modification takes the direction of an increase of the cells at the expense of the fibres, we have a fibro -cellular tumour. The tumour is composed of elongated elements, which are virtually nucleated cells with very· long bodies, ∣ amounting almost to fibres. The figure (fig. 21) is made from an extensive tumour deeply seated in the carotid region of the neck in a woman aged twenty-two.

There is nothing more remarkable in all these varieties of tumour than the constancy of the warp-and-woof texture, and we shall find that the same is an important characteristic of the class of tumours where the fibrous structure is wanting and everything becomes cellular. Tumours of the latter kind form the group of sarcomata or flesh-like tumours. Proceeding from the fibro-cellular tumour last mentioned and sketched, we come to the variety of spindle - celled sarcoma, in which the cells differ from the fibro - cellular elements of the former, chiefly in the greater prominence of the nuc- ∣

leus and the greater delicacy of the tapering prolongation of cellsubstance. It is sometimes called a small spindle-celled sarcoma. The figure (fig. 22) shows the structure to be purely cellular, without any fibrous supporting tissue. In the cross-section the spindlecell appears as a small round cell.

In the sarcoma with large spindle-cells we have a form of tumour not uncommon in certain regions of the body, often associated with brown pigmentation, and very generally malignant in its course. One common seat of it is the choroid coat of the eye, where large pigmented cells, both spindle-shaped and branched, exist naturally. An other common seat is the subcutaneous tissue, where pig- ' mentation is not a normal occurrence. The illustration (fig. 23) is taken from a case where there was, however, brown pigmentation of the skin for a considerable distance round the tumour. The situation was the shin, the common seat of chronic ulcers, and the tumour seemed to have begun in the scar-tissue of an ulcer of that kind. The cells are very large spindle-like elements grouped in decussating bundles, the distribution of pigment being partial (omitted entirely in the cut), and not uncommonly confined to the narrow bands of cells separating two broader or thicker bundles. The developmental or embryonic character of these cells is sufficiently obvious; but the occasion for their reappearance in mature life is not so clear. For the particular case of tumour over the shin the following may be conjectured. In the pigmented scar of an old ulcer of the same region the subcutaneous fibrillar tissue is found to be thickly occupied with large spindle-cells full of brown pigment granules (see fig. 15). Now, the skin for some distance round the tumour in question had precisely the brown pigmentation of a scar that had re-formed repeatedly, and the brown colour resided presumably in the same embryonic elements as are drawn in fig. 15. It cannot be supposed, however, that that explanation applies to all spindle-celled sarcomas with pigment, even if we do not include those of the choroid tunic of the eye. A more general explanation must be sought for the pigmentation, which-will apply also to the pigment in scar-tissue itself.

Cystic Sarcoma. — The activity of tumours, even of those classes that we have hitherto considered, is not purely structural or formative; it may be obviously functional, involving an instability of the structure. Even the fibrous tumours may become cystic in theiι ’, interior, as notably in the case of fibroids of the uterus; and it may be stated generally that all such traces of cyst-formation in solid masses of embryonic tissue are so many traces of the deeply-rooted embryonic function of those tissues. This important principle of tumour pathology may be conveniently introduced through a particular case of spindle-celled sarcoma, which grew to a great size on the outer side of the thigh of a boy aged fifteen, having its root deep down in the interval between the tensor fasciae muscle and the vastus externus. In no part of this tumour were traces wanting of an embryonic function residing in its component cells. Although the section of the tumour was close and firm, yet one found under the microscope the appearance drawn in the figure (fig. 24). The tracts of spindle - celled tissue are interrupted by spaces lined by cubical cells, which are the surface-modification of the spindle-cells. These are the blood-spaces of the tumour, and blood is to be seen in them here and there. Where the excavation has been extensive the spaces have formed communications, and left the spindle-celled tissue projecting into them as free cylinders or columns, with rounded ends covered with the same cubical epithelial-like elements. A central area of the tumour was more spongy in consistence; and that character is found to depend upon the greater development of the spaces, approaching remotely to a cystic development. It is here that one sees the true physiological or embryological significance of the interstitial spaces, of their contents, and of the cubical cells round their walls. The surface-row of cubical cells loosen from their attachment, fall into, the space, and are succeeded by another row, which are detached in turn; and so the excavation proceeds at many centres. The detached cells do not remain free solid elements; they may sometimes change in toto into a mucous fluid, but their full physiological activity is the haematoblastic or blood-making. The spaces contain the haematoblastic cells and their derivatives in various forms. One may see the cubical cells on the margin of the space (fig. 24) acquiring a yellowish tint, then the same cells disengaged and lying free in the space and probably increased in size (fig. 25), then red blood-disks of the same colour as the protoplasm of the haematoblasts, and cells -with several nuclei corresponding to those already described as the surviving nuclei of the disintegrated haematoblast, the whole lying in the midst of a mucus-like coagulum. This is neither more nor less than the early blood-making function of the mesoblast revived. The result is not by any means always or altogether blood, and in cysts it is indeed for the most part a mucous or serous fluid.

In one direction this process goes on to the ultimate destination of a thin-walled cyst ; and the following case of spindle-celled sarcomatous tumour may be regarded as an interesting intermediate phase. The tumour is the size of an orange, from the neck region of a dog; the peculiarity of it is that it is excavated completely on the side next the skin, while the deeper half of the sphere is made up partly of a firm texture with slits or spaces lined by cubical cells, as already described, and partly of a beautiful interlacing system of polished cylinders crossing the cavity from side to side, or hanging free into it. The process of excavation has merely been an extension of that drawn in fig. 24; it may be compared to the excavation of the heart in the embryo,—the columnae carneae and musculi papillares and pectinati of the latter corresponding to the columns and free projecting cylinders of the cyst. It is noteworthy that a trabeculated interior is characteristic of many cysts.

Myxoma or Mucous Sarcoma.—In another direction the haematoblastic softening process goes on to the variety of tumour called myxoma or mucous sarcoma; and this change may be actually observed in parts of the above-mentioned extensive spindle-celled sarcoma from the outer side of the thigh. A myxoma is that particular modification of embryonic mesoblast in which the softening or fluid disintegration takes place, not along definite or selected tracts, but uniformly over a particular area. The cells become excavated somewhat as in fat formation, the nucleus remaining at one side, and their thin membranous walls appearing as branching processes, which join with those of the next cell. Hence the nuclei often lie as if at nodal points of a meshwork of fibres, and they are often triangular or lozengeshaped. This is one common form of myxomatous tissue. But the mucous transformation taking place in each individual cell may result in a tumour presenting a very different appearance. The figure (fig. 26) is taken from a soft gelatinous tumour of the subcutaneous tissue. Nothing could be more orderly than the grouping of its large mucus-yielding cells in rows following the waved course of the bundles of fibres or fibrils; they are as regular as the cellplates of tendon. Their origin can be traced to the fixed connective-tissue cells of the part, which have emerged from their inconspicuous state, and have acquired breadth and thickness, a cubical form, and mucus-yielding protoplasm. Precisely the same process may end in a cystic excavation. The relation of this change to the indwelling tendency of the mesoblastic cells towards blood-making is revealed in the actual haematoblastic character of the cells here and there, and in the blood-disks and cells with cleft nucleus lying around. Another intermediate or occasional form of the cells in this tumour reveals also the true affinities of spindlecells filled with yellow or brown or black pigment. Such pigmented spindle-cells replace the mucous cells here and there; we must consider them to be also a somewhat devious development in the haematoblastic process, their pigment being practically the same as blood-pigment.

Alveolar Sarcoma.— In this connexion also we must take the kind of tumour that is often called alveolar sarcoma. The epithelial-like form of cell, which lines the spaces among the spindle-cells in the case already mentioned, now comes to predominate. The following is an instance, with figure (fig. 27). A tumour the size of a large walnut, deeply pigmented, with the skin drawn tightly over it as if it had grown in the position of a mole or congenital mark, was removed from a man’s leg. Although the tumour is somewhat black throughout, the pigment is found to reside only in certain narrow tracts or clusters of cells. The structure is divided into oblong or alveolar spaces by narrow bands of fibres, the cells within the spaces being all of the epithelial type. Some of the cells are much larger than others, and these largest elements are tinted bright yellow or brown. It is no great step from this singular structure to the embryonic structure and function of former cases. Instead of a few cells at a time forming an epithelial-like surface to an alveolar space (the great bulk of the tissue remaining as tracts and columns of spindle-cells), here the alveolation has been general through the whole area, and all the cells have become as if surface-cells. Furthermore, they have been fixed in that condition, proceeding to no further development, whether mucus-forming or blood-forming,—only certain groups of them, and these by far the largest and most epithelial-like, acquiring the yellow colour of haematoblasts, or a brown colour. The pigment is otherwise contained in spindle-cells which occupy the interalveolar septa, and in them it is in a more granular form.

Cavernous Blood-tumours.— The pigmented alveolar sarcoma is sufficiently common in the situation of congenital mother-marks of the skin to be one of their characteristic developments. Another of their developments or equivalents is the naevus or aηηeioma or cavernous tumour, whose structure may be said to consist, in general terms, of a spongy meshwork of alveolar spaces, bounded by coarse and elastic trabeculae and filled with blood. Arteries open into such tumours and veins pass out from them, the cavernous territory being intermediate; but, according to several authorities, this connexion with the circulation is not primary to the cavernous tumour but acquired. Without entering upon a discussion of details, the analogy of the alveolar sarcoma growing on the same basis of a congenital pigment-spot may be kept in view. The β alveolation is the same in both cases, although the trabeculae in the cavernous tumour are somewhat stouter, the grand difference being in the contents. If, however, we suppose the epithelial-like cells of the alveolar sarcoma all to become large and filled with a yellowish colouring matter, as indeed many of them do, and if we suppose that these haematoblasts (for such they are) go on to fulfil their destiny, then we should have a cavernous blood-tumour, that is to say, the alveoli would be filled with red blood-corpuscles. It will not be possible to offer evidence of this process except for the cavernous blood-tumour of the liver, an organ in which such tumours are comparatively frequent, and mostly in later life. The cylinders of liver-cells appear to become narrower and narrower, as if from pressure of the capillaries, and ultimately to disappear. From the supporting tissue a new growth of cells takes place (fig. 28). These are haematoblasts; their protoplasm becomes red blood-disks, and their nucleus survives with the remarkable trefoil arrangement of cleavage which has been described for several other instances of the haematoblastic process. There can be no mistaking the identity of this process with that of the blood-cyst of the neck already mentioned; it is essentially a manifestation of haematoblastic function late in life, differing from that of the blood-cyst in the fact that the centres of blood-formation are separated from one another within alveolar boundaries. These cases illustrate another striking property of cavernous blood-tumours, namely, to heal spontaneously in parts or to develop embryonic scartissue through more or less of their extent (fig. 29, a). The ordinary cavernous texture of an angeioma is produced by the formative process stopping short of embryonic connective tissue or scar-tissue. The accompanying figure (fig. 29, b) is from an enormous angeiomatous tumour on the side of an ox’s head; the structure is very like that of the young connective tissue of the former figure, except that the meshes are densely packed with red blood-corpuscles. There are, however, other parts of the tumour where the fibres are broader, the meshes narrower, and with embryonic cells lying in them, instead of or along with blood-corpuscles.

There is no definite limit between such cavernous blood-tumours and true blood-cysts; in the latter the numerous haematoblastic centres open communications, and the further process takes place in the cellular tissue forming the cyst-wall.

The blood-making office of the mesoblast is the earliest and greatest of the functions of embryonic cells, and it is not surprising that it should come out more or less obviously in those formative processes in the common binding tissue of the body where there is a persistence or revival of embryonic activity. We seem to find traces of it in the pigmentation, in the cystic excavation, in the alveolation, in the mucous or myxomatous transformation, and in the cavernous structure of mesoblastic new growths. The embryonic spontaneity in the middle layer is, of course, wider than mere blood-making; but the haematoblastic function or tendency is certainly the most fundamental, and the traces of it in the foregoing tumours are our best help towards a rational interpretation of them. Persisting or revived embryonic activity in subcutaneous and other homologous tissues cannot but bring to light more or less of this all-important mesoblastic function; the memory of it is too strong to be ignored. We come next to a function of embryonic cells which is only second to the haematoblastic, namely, the osteoblastic or bone-making function; and even with the bone-making process the earlier blood-making process is deeply interwoven, for in the marrow of the bones the haematoblastic activity of cells persists long after it has ceased elsewhere.

The bone-making function of embryonic tissue—if function it may be called—comes into a large number of tumours; or, in other words, a large proportion of all mesoblastic tumours are tumours of the bones. In all of these the embryonic law of development and growth is clearly present. The results, however, are frequently more complex than in the tumours hitherto considered; or, in other words, tumours of the bones are exceedingly liable to have a structure so mixed as almost to baffle systematic description. One reason of this is that the osteoblastic and haematoblastic functions of embryonic cells go hand in hand in their production; and the complexity of structure is, accordingly, greatest in those which grow from that part of the bone where the blood-making resides, namely, the marrow. The other great formative tissue of bone is the periosteum, a tissue which retains its embryonic structural features long after the mesoblastic tissues elsewhere in the body have lost theirs. The marrow and the periosteum are frequently involved in the same tumour; or an essentially similar morbid product may be derived from either. That is notably the case with the tumours of the bones which we come to first, the cartilaginous tumours or enchondromata.

Ecehondrosis.— It is only rarely that a cartilaginous tumour grows from cartilage, the observed instances having occurred at the cartilaginous lines of union of the base of the skull, at the epiphysial lines in long bones, and in such permanent cartilages as those of the larynx and trachea. To these direct outgrowths of cartilagecells Virchow has given the distinctive name of ecchondroses. Usually the cartilaginous tumours do not grow from pre-existing cartilage; they grow either from the periosteum or the marrow of the bones, or they form in certain glandular organs, especially the salivary glands (parotid, labial, &c. ), the mammary gland (oftenest in the dog), the lacrymal gland, the testis, &c. These latter enchondromata are a class apart, involving considerations of disordered everyday secretion rather than of the revival of embryonic activity (see “Errors of Secretion,” p. 379 below). The enchondromata that fall to be considered here are those which grow within or upon the metacarpal bones and the finger-bones, more rarely in the corresponding bones of the foot, not unfrequently in the bones of the face, and, it may be, in the leg-bones and arm-bones, or in bone anywhere.

Enchondroma. — The simplest cases (but the least frequent) are those that form between the periosteum and the hard bone from the growth and transformation of the cells of the periosteum, being directly homologous to the ensheathing cartilage-callus of repair. They differ from the cartilage of repair in precisely the same way that a granulation-like sarcoma differs from the granulation-tissue of repair,—that is to say, the existence of the tissue is not selflimited, or it has no tendency, or only a feeble tendency, to cicatricial modification, shrinkage, or absorption. These purely subperiosteal enchondromata are said by Paget to be nearly characteristic of the ends of long bones, although they do not encroach on the articular cartilage. When a cartilaginous tumour occurs in the shaft of the bone it is partly subperiosteal and partly in the marrow; and in the most characteristic seat of enchondromata, the bones of the fingers, the growth is entirely in the marrow if the tumours are multiple; but, curiously enough, it is subperiosteal if there is only a single tumour (Paget). There are also cases where islands of cartilage form in the compact substance of the bones, corresponding to Haversian systems.

The tissue-affinities of a cartilaginous tumour glowing between the [>eriosteum and the hard bone are not difficult; the homologue, as we have said, is the callus-cartilage of repair. The histogenesis and physiological analogies of an enchondroma of the medullary canal of a bone are less easy. We know that the marrow was preceded, in the development, by a bluish rod of foetal cartilage, of which all characteristic traces had disappeared before birth. As the blood-vessels entered it, it had changed into a spongy kind of bone, in whose spaces lay many spherical nucleated cells retaining a haematoblastic or blood-making function; all the spongy bone is gradually absorbed in the shaft, the last traces of it being a few spiculae on the hard inner wall of the medullary canal, and the cavity is occupied by a highly vascular substance, the red marrow characteristic of young bones. The spherical cells of the red marrow become excavated into fat-cells, and the red colour changes to yellow. It is probably in this final phase of the development inside the shaft of a bone that we must look for the opportunity of the central enchondromata forming. The secret of the return to cartilage in some cases, and at certain spots, probably lies in the change of red marrow into yellow; instead of becoming fat, it becomes a kind of cartilage. The tumours in question are most common, at least, just at the time of life when that change in the character of the marrow takes place. Again, at the spongy ends of bones, where the marrow remains red, the internal enchondromata rarely occur (a case is quoted by Paget at the lower end of the fibula), but chiefly the subperiosteal. If the enchondromata were composed of a definite type of cartilage, and, above all, if they were stable in their structural characters, the relation of them to the marrow of bones, which these facts point to, would not be a very intelligible one. But the enchondromata are rather a kind of new growth in which there is a good deal of gristly substance of one kind or another, associated with a good deal of mucous or myxomatous tissue, with cystic spaces containing mucous or honey-like fluid, and even with blood-spaces. Besides the myxomatous tissue, there may also be tracts and areas of other soft tissue made up of spindlc-celïs, multinuclear cells, and various nondescript forms; and, most significant of all, there may be much of the cartilaginous substance quite faetal in its characters, —that is to say, consisting almost entirely of cells, with a small amount of more or less tough hyaline intercellular substance. Fig. 30 shows a highly cellular kind of cartilage from a tumour of the u PP er J aw °f a horse. The next cut (fig. 31) is from a cartilaginous tumour of the upper jaw of a woman; it shows cartilagecells with definite capsules, and surrounded by a kind of tissue which would be called myxomatous. The shades of difference among the tissues of enchondromata are indeed endless. They may be said to be all possibilities open to the red marrow (haematoblasts) on the way to become fat; sometimes one devious route is taken, sometimes another, and the result may be soft mucous tissue, various forms of cartilage, or true bone as an ulterior development of the cartilage.

Osteoma.— Next to the enchondromata among the tumours of bone we may take the osteomata, or outgrowths from the bone which have themselves the structure of true bone. Their most common form is the exostosis, an osseous node or spine, or rounded tumour generally, on the outer surface of a bone. Sometimes an exostosis is found covered by a considerable cap of cartilage; and, whether it be or had been partly cartilaginous, or whether it be entirely osseous, it is a product of the periosteum, and it illustrates the ordinary osteoblastic function of that tissue. Sometimes the exostosis is spongy, at other times it is hard as ivory, the flat bones of the head being the favourite seat of the latter variety.

Osteoid Tumours {Subperiosteal Malignant Tumours).— By far the most important of the tumours of bone are those which are composed of a crude kind of bone, or of various kinds of soft tissue which show a more or less feeble tendency to osseous transformation. These tumours of the bones are apt to occur during the growing period, or shortly after growth has ceased; they are by no means rare, and are often fatal. Like the enchondromata, they are divided into those which grow under the periosteum, or the external tumours of bone, and those which begin in the medullary canal, or the internal. The former are much the least complex; and, like the subperiosteal enchondromata, they are mostly found at the ends of long bones, especially at the end of the femur. The growth is clearly subperiosteal; the outlines of the compact bone of the shaft can often be seen running through it. The structure of this kind of tumour is tolerably uniform; it is not bone, but an irregular product of the periosteum to which the name of “osteoid” has been given. The structure is that shown in fig. 32. There is a network of slender trabeculae, mostly forming long parallel meshes, and with numerous but less conspicuous cross subdivisions; these are impregnated with osseous salts; but it can hardly be said that bone-corpuscles are embedded in them, as in the normal growth of bone from periosteum (fig. 33). The cells which correspond to the osteoblasts are ranged along the sides of these trabeculae and in the spaces between them; but they fall short of the true osteoblastic grouping, and they seldom become bone-corpuscles embedded in an osseous ground-substance. This is a peculiar error of the osteoblastic process, but a not unintelligible one. It may be further illustrated by another form of periosteal tumour in which there was no deposition of the hardening matter at all. This tumour (fig. 34) grew around the metatarsal bone of the little toe, and, like the osteoid kind of tumour last described, it had a power of infecting the neighbouring tissues and even distant organs, which need not be dwelt upon at present. The structure is a strange reminder of the inherent osteoblastic function of the periosteum from which it grew. There is not a particle of osseous or earthy matter in its substance; but it has the trabecular type of osteoid tissue, and the cells have the surface-grouping of osteoblasts. _ They are the elongated or spindle-shaped cells of the periosteal tissue, which have become more cubical and angular, and have formed rows of free cells round the walls of the interstitial slits or alveolar spaces. The difference between this and an osteoid tumour is that a certain attempt has been made in the latter towards true bone in the deposition of earthy or bone salts in the trabeculae. In the case of the soft tumour of the periosteum there were clear traces of rickets in infancy, and the essential thing in rickets is the tardy or inadequate deposition of earthy matter in the growing bone. In both tumours the formative activity of the periosteal cells outruns their osteoblastic and ossifying functional activity, so that the latter is always behind, and the perfect result of hard bone is never attained. How this error makes a malignant tumour is another and more difficult question.

Myeloid and other Internal Tumours of Bone.— The foregoing are representative instances of externa! or subperiosteal tumours of bone in addition to the enchondromata and osteomata. There remains an important group of internal tumours, or tumours of the bone-marrow; and these, with the corresponding group of internal enchondromata, exhaust the morbid new formations incidental to the growth of the skeleton. There is, indeed, no hard-and-fast line between the enchondromata and the internal tumours of bone; the latter have almost the same mixture and confusion of structure in various parts that the cartilaginous tumours have. The principal seat of the soft tumours of the bone-marrow is the lower end of the thigh-bone, the ends of the other long bones being the next most favourite seats. A certain tumour of the jaws, the myeloid epulis, is also classed with them. The tumour often grows quickly, and may attain an enormous size; it causes the absorption or transformation of the hard walls of the bone, and there may be nothing between it and the skin, muscles, and tendons but a more or less continuous thin shell of bone. The interior has a most diversified aspect. Many patches are friable and yellowish, other areas are a livid purple and gelatinous, and there are often blood-clots and cystic spaces filled with a tenacious brownish mucous or colloid fluid. Amidst these softer parts there run tracts of more spindlecelled or fibrous tissue, and there are often islands of cartilage, or fragments of osteoid substance. The only clue to this puzzling diversity of texture is the inherent range of possibilities in the function of the bone-marrow. Derived from embryonic mesoblast, it began as a temporary foetal cartilage; it then became spongy bone tilled with ml marrow, in which state it remains in the ends of long bones, in the diploe of flat bones, and in the interior of bones like the vertebne. In the shafts of long bones the trabecnlíe of bone are all removed and only red marrow remains, with a pronounced haematoblastic function; but, when growth is well advanced, the cells of the red marrow become excavated to fat-cells, their blood-forming function ceasing therewith. We have also seen that, in the process of repair, the marrow and its blood-vessels together are able to produce new bone between the broken ends. There are here memories enough to produce very fantastic results if anything should arise to recall the developmental activity. Disregarding the livid or blood-like patches, the mucous areas (whether myxomatous tissue or colloid fluid), and the fragments of cartilage and of osteoid tissue, some of which have l>een spoken of above, let us consider the tissue that is. most characteristic of this group of internal bone-tumours. It is the yellowish or sand-coloured areas of friable texture, corresponding to the tissue named by Paget “myeloid,” or marrow-like. Its name is due to the fact that it always contains a number of multinuclear cells, giant-cells or mycloplajces, such as are found in the marrow of young bones. Its yellowish colour is almost sufficient of itself to indicate the presence of these elements. The cut (fig. 85) shows several of these myeloplaxes lying among cells of various shapes with a single mìcleus. In one direction it is no great step from this to myxomatous tissue or other haematoblastic modifications; and in another direction it is no great step back to cartilage. We shall probably not go very wide of the mark if we take the common starting-point of the various tissues to be foetal cartilage, as drawn in fig. 30 from an enehoudroma of the upper jaw; and, given foetal cartilage, it is not difficult to follow it along the various lines of its historical development in the shaft of a bone, to imagine the development taking a devious turn-at one point or another, and so to account for the heterogeneous structure of the tumour,—some of the structure, indeed, being strange to the normal types of growth.

Dermoid Cysts.— Having now illustrated two great instances of embryonic function revived in after life to the production of tumours—namely, the blood-making and the bone-making functions —and having therewith disposed of a considerable number of all the tumours that have a mesoblastic homology, it will be convenient to advert to a remarkable kind of tumour which shows to the fullest extent what the embryonic mesoblast can do in the way of fantastic new productions, namely, dermoid cysts. Not only blood and bone, but teeth, skin, hair, glands, muscle, and nerve are produced as the tumour-constituents in these remarkable new growths. Their usual seat, and the invariable seat of the most perfect of them, is the ovary; and the ovarian is just that mesoblastic tissue upon which the memories of development are as if concentrated; for it is from an ovarian cell that the embryo grows in the perfect likeness of the parent These selected cells of the ovary, or, in other words, the ova, are specially charged with the recollections of the past history of evolution and growth; and the rest of the ovary appears to [κ>ssess the same lively memory, if not to the same extent, yet to a much greater extent than mesoblastic tissue elsewhere. The stroma of the ovary is the best example in the body of embryonic spindle-celled mesoblast; only in some animals does it become normally fibrous, and in any animal it may revert to embryonic characters with the greatest ease at the generative periods or at other times, and even in extreme old age. But for the fact that the tissue keeps within normal limits of form and extent it might pass muster for spindle-celled sarcoma, in all respects, including the warp-and-woof arrangement of the tracts of cells. From this tissue cysts are developed interstitially, and they are not the less -interstitial in their development that their homologue is often, if not always, a Graafian follicle. That, however, is a region of controversy, and it will be more convenient to take an unambiguous case first Such would be a dermoid cyst under the skin, say in the neighbourhood of the orbit It is true that even these cases are sometimes explained by assuming that the skin has somehow become involuted at the particular spot during development; but no observed facts warrant this assumption, and the histogenetic facts of the new growth itself are entirely against it. Fig. 36 shows a portion of new-formed skin on the wall of a small congenital dermoid cyst over the external angular process of the frontal bone; adjoining the actual skin there may be seen the interstitial cells of the connective tissue becoming adapted in form and arrangement to continue the layer of rete mucosum over the cyst-wall beyond. The adaptation is very much the same which has already been mentioned with reference to the new skin of a granulating surface; the connective-tissue cells become large and cubical, often multinuclear, and elongated towards the surface. The supply of these formative cells comes from the connective-tissue elemento lying among the parallel fibrous bundles of the cyst-walL

For ä dermoid of the ovary it is impossible in a brief space to give any idea of the marvellous' textures that are being woven side by side in various parts of the cyst-wall,—the areas of foetal cartilage, the interlacing bundles of plain muscular fibres, the long rows of pigment-cells, and, not far off, the rows of mucous cells developed interstitially, and maturing so as to be fused into the fluid of subordinate cysts. At one place there is a piece of skin, underneath which will be found an enormous development of sebaceous glands; where the skin ends a brownish velvety patch begins, with no sebaceous glands, although there are rudimentary hairs at various depths. This under the microscope will be found to approximate to granulation-like tissue, with many variously-shaped pigment-cells, and corresponding probably to the congenital mother-marks of the skin proι>er. It must suffice to give a single illustration of the strange formative activity of this mesoblastic tissue, namely, the formation of hairs. Hairs in dermoid cysts are formed in a very peculiar manner. It is usual in subcutaneous dermoids to find them embedded parallel to the surface at various depths in the midst of multinuclear or giant-cells. Some of these multinuclear masses may be seen undergoing a vitreous transformation down the middle, as in fig. 37, a ; elsewhere may be seen the same peculiar central rod extending through a succession of giant - cells; and, most remarkable of all, there is the appearance drawn in e. In this last case the vitreous rod is capped at each end by a giant-cell, and the characteristic imbrication of scales has developed on it over the intervening length. Tire cross section of such a hair is seen in d. The section of hair is evidently a part of the multinuclear cylinder; it is in this instance well to one side, but it is still enclosed by the marginal nuclei of the cell, which are flattened into plates upon it; in other instances it is found lving outside the largest of à cluster of giaut-cells and surrounded by the smaller ones. The nature of the transformation in the heart of these multinuclear blocks is not easy to determine; the most striking circumstance is that other giant-cells, which appear to be advancing in the same direction, or to have diverged from the same kind of development, have an area of deep-brown or orange pigment in their centre instead of the vitreous or horny transformation,—the marginal belt being free from pigment. This is a peculiar formative use of giant-cells. We have already seen that they are used in the vessel-making processes of the placenta and of repair; we have seen also that they may be the media through which a granulation-surface acquires a covering of epidençis; and here we find them playing the part of hair-follicle.

A dermoid cyst reveals the surprising spontaneities of a collection of embryonic cells of the mesoblast,—the inherited traditions of their life,—manifested in diverse ways side by side, and manifested often feebly and grotesquely. There is no reason to seek for the source of these various products beyond the stroma of the ovary itself; and the variety of the products must be a measure of what that kind of tissue can do in the way of new formation. When various kinds of structure are thus brought together in their development we have an evidence, not only of the indwelling power of mesoblastic tissue to revert to embryonic modes of life, but also of a common starting-point for structures that come to be very unlike. We may note, among other things, how small a step there is from the production of blood and blood-pigment on the one hand to that of hair on the other.

§ 5.— Errors of Development and Growth in General.

The more usual departures from the normal type in the embryological rudiments or in the growth of particular organs and parts of the body have been already described in the article Monster. The present section will be devoted to those errors of development and growth which amount practically to constitutional diseases.

Rickets.— We have hitherto considered the indwelling spontaneities of the cells and tissues as manifested in the process of repair, and manifested capriciously in some tumour-processes; in these it has seemed as if the blood-making function of the embryo were the most fundamental of all its primitive tendencies, traces of it being found in the reparative process and in the new growth of tumours. Next to it, and even bound up with it, is the bone-making function; and we now come to a general or universal disorder of the bone-making function in which these developmental doctrines will be found to have a useful application. This disorder is rickets, a common malady of infancy and childhood. Attention was first drawn to it in 1650 by Glisson, who spoke of it as a disease of children that had been known to be endemic for thirty years in Somersetshire, and had been brought from the country to London. It is very common in all great cities; in Vienna it is still known as “die Englische Krankheit.” A child developing this error of growth becomes profoundly affected in its health generally. It is tender all over, dislikes to be touched or handled, throws off the bedclothes even in cold weather, perspires profusely about the head, moves its head restlessly in sleep, so as even to wear the hair off, and in its waking hours sits perfectly still and subdued under a kind of suffering which can be but half - realized by its. consciousness. Such children give little trouble, seldom crying even when left alone. They are very sensitive to cold, and proportionately liable to catarrh; their nervous impressibility also is heightened, making a peculiar liability to convulsions and to laryngismus stridulus. They are “backward children,” and, in particular, late in getting their teeth.

The conspicuous error in such subjects is in the growth of the bones everywhere throughout the body. The rickety condition often begins in children who are plump and apparently well nourished; and, if the nutritive and other processes are involved at length, it is the osteoblastic process that is primarily at fault. The details are somewhat different for the two kinds of ossification—in membrane or periosteum, and in cartilage. Regarding the former, the error will be readily understood by reference to the accompanying cut (fig. 38) of normal ossification of the parietal bone. The spindle-cells of the membrane are becoming cubical along a line a little below the surface, and a few of them are half-included or imprisoned in the thin bar of bone; most of them are free on the surface of the calcified bar, as osteoblasts, the included ones being bone-corpuscles. Increase of the osseous tissue takes place through other osteoblasts becoming surrounded by calcifying ground-substance; and, in the broader bars of bone below, the bone-corpuscles may be seen to be two or three rows deep. This process goes on until the whole of the osteoblasts (derived from spindle-cells) have been included one by one within the calcifying matrix; once included, these cells are incapable of growth; the multiplication is always in the spindle-shaped cells of the membrane, or on the surface of the bony bars or trabeculae: and the inclusion is of that gradual and co-ordinated kind that there is always a set of free cells left on the surface to keep up the succession of formative elements. It is not until growth is completed that osteoblasts cease. The error in rickets is that the multiplication of spindle-shaped cells and osteoblasts far outruns the calcifying process. Instead of these elements being produced only as fast as they are wanted for inclusion as bone-corpuscles, they are produced regardless of the forwardness of the calcifying process, upon whose exact co-operation with the cellular formative process all true periosteal bone-making depends. The error, or part of the error, of rickets is that the calcifying process is behindhand. A large quantity of soft bone-making material accumulates, which would, under ordinary circumstances, have become hard bone as soon as it was formed; sooner or later it becomes bone, even, in rickets, but the deposition of earthy salts is slow, and in the meantime the bones have become bent. Not only is there a relative slowness in the calcifying process, but there is an absolute excess of the cellular elements or of the osteoblasts; and, in the flat bones of the skull, this is shown in the thickness of the bones ultimately, especially along their growing edges. The same excess of formative material beyond what can be used up for bone is seen in the ossification from cartilage at the epiphysial line. The cartilage-cells divide and multiply at an excessive rate, and the columns of them, instead of keeping in the line of the axis of the bone, radiate to the sides, so that there is often a bulbous enlargement where the epiphysis joins the shaft. The want of harmony in the calcifying and osteoblastic parts of the process is shown by the irregularity of the epiphysial line (fig.

39); it is a straight line normally, but in rickety growth it runs out and in, cutting off islands of cartilage in the midst of spongy bone; and this irregularity is due to the fact that the blood-channels in the cartilage are formed sooner at some points than at others, the calcification following close on them. In the shaft of a long bone the process is the same as in a flat membranebone of the skull; the periosteum is thick and its inner layers are blood-red, and in extreme cases there is what looks like a stratum of blood between it and the bone. Bone is at length formed from this layer, but it is of the spongy kind, so that the shaft is softer and more porous on the outside than on the inside. In the flat bones of the head, also, the structure is apt to be of the spongy kind throughout, so that they consist as if of diploe entirely, and not of a layer of diploe between two hard plates. Sooner or later, under favourable circumstances, the spongy bone is replaced by compact bone, and in the end the bones of a rickety subject are harder and thicker than usual. In the worst cases deformities remain, notably the bent spine, the pigeon-breast, and the deformed pelvis. In the very worst cases the stature is dwarfed and the long bones are bent and twisted.

Analysing these phenomena and filling in details, we come in the last resort to an indwelling disposition, probably acquired in most cases, or in largest measure, before birth. These tendencies come to an issue in the skeleton, because the growth of the bones is of a nature to tax the organism. The growth of the bones is the great instance of metaplasia; it is a succession of tissue - changes long kept up, and it requires a peculiar co-ordination or orderliness at each step, owing to the fact that stiffness has to be combined with plasticity. The requisite stiffness can only be got step by step through the sacrifice of that plasticity which goes with growth, and hence the special adaptation of a free row of osteoblasts on the surface of bone-trabeculae to ensure the apposition of new layers. Cartilage gives the stiffness for a time in all the bones except the clavicle and those of the vault of the skull; having served its purpose, it becomes spongy bone, blood, and marrow, the spongy bone being finally removed in the shafts of long bones, the marrow remaining, and the blood continuing to be added to the general blood of the body. In these adaptations the early importance of blood-making among the embryonic cells is duly asserted. When the foetal cartilages have served their turn the haematoblastic function becomes prominent in the cells, and a large part of all that was cartilage literally becomes blood. According to numerous observers, it even becomes blood without the accompanying formation of blood-vessels with definite walls. Some of it becomes bone; but the bone is in thin plates only, and much of it is ultimately removed. In the periosteal process, also, where the cartilage-stage of the formative tissue is never gone through, there are not wanting indications that the same haematoblastic function is present concurrently with the osteoblastic.

Coming, then, to the actual facts of rickets, we shall find that those features of the process on which the greatest stress has been laid in the recent elaborate researches of Kassowitz are of the nature of over-vascularization or hyperaemia. In the ossification from cartilage he finds that the vessels from the perichoridium extend inwards to a greater extent and with less orderliness than usual; then there is a development in the cartilage of colossal vessels, and finally of blood-spaces, packed full of red blood-disks, and with no very definite walls, so that it looks, at the first glance, as if haemorrhage had taken place into the bone-marrow. In many cases there is no sharp line of separation of the embryonic marrow from the contents of these blood - spaces; it is probable that the gelatinous tissue of the former had “passed direct into haematoblastic substance and so into blood-corpuscles.” In the periosteum also there is much more blood than usual, and the same large bloodspaces are sometimes found. These errors of vascularization Kassowitz places at the foundation of the rickety process. Deposition of calcareous salts, he points out, cannot take place where there is so much blood; the calcification follows in an orderly way only where the movements of the blood and juices are restrained or distant, the best example of this law being the gradual reduction of the wide central space of an Haversian system to a narrow channel containing a single twig of blood-vessel.

The excess of vascularity in rickets is, by Kassowitz, put down to “inflammation,” or to the hyperaemia of the same; but we have seen that he also invokes, as a detail in the process, an excessive haematoblastic activity in the embryonic marrow-cells. The latter is a more fundamental and intelligible fact than “inflammation” (which begs all the fundamental questions), and we shall do well to give it prominence accordingly. λVe should then interpret the observations of Kassowitz as follows.

The due regulation of the blood-supply, the restriction of it to definite and ever-narrowing channels, is necessary for the proper deposition of the earthy matter and for the building up of bone in Haversian systems. The embryonic cells surrender their individual haematoblastic function, while certain tracts of them become definite vessels for the supply of all the rest; and in proportion as they give up individually their primitive function of blood-making they are in a position to take on individually the function of bonemaking. In compact bone this change of direction is carried out most completely; the cells become osteoblasts in successive rows, a ground - substance impregnated with earthy matter closes in around them, and they are imprisoned for ever as bone-corpuscles. In spongy bone, however, there is still a reserve of haematoblastic force; only thin laminae of bone are formed out of some of the cells, while many of them continue to be haematoblasts and to form the familiar red marrow. Adopting, then, the figure of a struggle between the haematoblastic and osteoblastic tendencies in embryonic cells, or the perception of a divided duty, we shall conclude that rickets is the undue preponderance of the former. It means spongy bone where there should be hard bone, and much wider spaces than usual, with much more blood in them in the proper seats of spongy bone itself; and it means in general a retardation of the hardening process.

All this enormous haematoblastic energy or local blood-formation is unfortunately wasted; the child is no better for it, and is more likely than not to be anaemic. The formative powers are diverted from bone-making, and spent upon blood-making; and the lime-salts in the organism that should have gone to make bone are actually thrown out with the urine, which has been known to have as much as four or even six times its due amount of phosphates. The organism, when rickets overtakes it, is in this fix, that it makes blood which it can no longer profit by, and has meanwhile to part with bone-salts which it will want again. The disease is, in fact, an unfortunate contretemps.

Many of the facts of rickets are thus secondary to an initial error in the embryonic functions of the tissues, and the evidence seems to show that the error must have begun in most cases before birth. Although it is well known that the obvious phenomena of rickets are not usually remarked until the child is a few months old, yet, as Kassowitz has ascertained, the condition “begins much more frequently than has hitherto been assumed in the later months of intra-uterine development.” The facts point very clearly to the health of the mother as being primarily at fault. “The health of the mother,” says Sir William Jenner, “has a decided influence on the development of rickets in the child. Whatever renders her delicate, whatever depresses her powers of forming good blood, that tends to produce rickets in an offspring. . . . The child of an ill-nourished mother is disposed to become rickety when placed under unfavourable circumstances after birth, or even under favourable circumstances in some cases.” The disposition must be in most cases, and in the worst cases, congenital in the child’s tissues. We should therefore seek in the intra-uterine connexion between mother and child for some defect on the maternal side which would induce that which would appear to be essential to rickets in the child, namely, a preponderance of the haematoblastic function of embryonic cells over the osteoblastic, a reversion in the cell-life of the growing frame towards independent blood-making. In seeking for this source of error, it will be necessary to recall for a moment the nature of the intra-uterine connexion between mother and child, or the part played by the placenta.

Placental Function in Congenital Disorders.— The embryo makes its own blood and establishes the connexion with the mother by its own blood-vessels. Its blood is carried to the placenta to be aerated, as the phrase goes; but it is much more than aerated. The placenta is a glandular or secreting organ of the mother, inasmuch as the maternal blood, flowing slowly through the spongelike tissue of thick-walled vessels, receives additions of mucus-like drops from the deliquescence of the large nuclei in the protoplasmic vessel-walls (fig. 40). This mucus-like addition is clearly an adaptation for the foetus; and the surfaces of the placenta, where the foetal vessels touch it, are further adapted, through a thick-set cap of nuclei, for exuding it where it can be taken up by the plasmatic tissue of the chorion. This placental contribution is the “uterine milk” furnished by the mother for the. use of the foetus, so that, although the latter makes its own blood (and bloodvessels), it receives material additions to its blood from the mother. It is obvious, therefore, that the secretion of the placenta is very essential to the foetus, and the due endowment of the latter must depend greatly upon the structural and functional sufficiency of that organ. ìt supplies the foetus with much of the fluid that circulates in the latter’s vessels; it may be said to spare the faetus to that extent the need of producing such fluid itself, or to dispense with the haematoblastic activity of its tissues, so that they may take other formative directions, such as bone-making. Or it may be contended that there are ingredients in the normal placental secretion which are specially adapted to bone-making. Now, if there should be any interference with these placental contributions, we are left to suppose that there must then be a reversion on the part of the foetal cells to self-helping tendencies, and especially to local blood-making. The excessive blood-making of rickets, and the retardation of bonemaking consequent thereon, would thus be traced to failure in the placental function.

But, if there be such a change in the direction of the formative processes of the foetus as an adaptation to its special intra-uterine conditions, why should rickets not become declared until several months after birth? In the first place, we have the evidence collected by Kassowitz that there are plain indications of the rickety process to be observed where death of the child has occurred before the full term; and, further, there are analogies to show that it requires all the extra-uterine functions to have been in action for some little time before a congenitally-acquired tendency manifests itself. Although the intra-uterine life comes to an end, and the child ceases to be dependent on the placental function of the mother, yet the acquired tendency, or the adaptation to a deficient performance of that function, remains for a certain time longer. It comes to an end, however, from the second to the fourth year; the bone-forming tissues cease to follow the devious direction, the bonesalts present in the organism are put to their proper use, ossification resumes its normal course, and, as the soft formative material of bone had accumulated in excess, the bones of the once rickety child are in the end harder and thicker than those of normal growth.

There is an assumption in the foregoing which calls for remark, the assumption, namely, that the placental function has been inadequate on the mother’s side or that the requisite additions to the blood have not been made. Our almost complete ignorance of the pathology of the placenta is the reason why the above-mentioned facts and principles have to be eked out by an assumption. We do, indeed, know that the placenta suffers in syphilis of the parent; and we know that in congenital syphilis of the child the growth of the bones is affected in many ways analogous to the shortcomings of rickets, and that, as in rickets, the error of growth may not show itself for some time after birth. It is highly probable that the placental structure and function suffer under many less special conditions of ill-health and mal-nutrition of the mother. The placenta is, in fact, a great formative effort, and the formative power cannot always be adequate. There are in particular two conditions in the mother favourable to rickets in the child, in each of which an absence of structural and functional perfection in the new-formed organ of intra-uterine nutrition is aprion probable. The one is the extreme youth or immaturity of the mother, assigned by Schönlein as the chief cause of rickets; the other is child-bearing up to a comparatively late period, the latest of a succession of pregnancies being often found to be those which yield the rickety members of a family. But amongst the poor there must be many other causes of general ill - health in the mother operating from time to time. Whatever makes the mother’s milk poor cannot but have told at an earlier stage upon the placental structure and function; and that earlier stage is a vastly more critical time for the endowments of the child,—for all its formative, nutritive, and functional tendencies.

Osteomalacia.— A sort of counterpart to rickets occurs in the disease known as osteomalacia or moÚities ossium; and, curiously enough, this is a disease (as distinguished from senile softening) almost exclusively of women during mature life, apt to occur in the gravid state, and especially if there have been repeated pregnancies. It is mostly a disease of poor and hard-worked women, just as rickets is a disease of the children of poor and hard-worked women; it is not very common, although it is said to be endemic in some localities. The bones become soft or friable, owing to the encroachment of the medullary cavity upon the compact substance and the further absorption of spongy bone; the encroachment may be so extensive that only a thin shell of bone or parchment-like membrane remains. This enormous medullary space is filled with marrow, but not the marrow of adult life. The marrow is of the foetal kind, red, and often containing areas of blood, abounding in nucleated marrow-cells, and with a decreasing number of fatcells. Ultimately the marrow becomes gelatinous. The process consists essentially of a reduction of the bone to red marrow, as in the first formation of the medullary cavities of long bones; the earthy salts are removed, and all the cells of the tissue acquire an embryonic character. Although there are some facts to show that this process takes place sometimes in the young, especially in young animals under confinement, yet its characteristic occurrence is in women during one of their later pregnancies. It is generally admitted that there is some intimate connexion between the outbreak of mollities ossium and the gravid state. We have found reason to conclude that there is an equally intimate connexion between rickets and the gravid state, only that the rickets is in the child. If, in rickets, the child is deprived of something maternal which it should have received, then in osteomalacia the mother parts with something for the child which she ought to have kept. In both cases the organism of the mother is overtaxed; but in the more general case, where the child becomes rickety, the tax has not been met. In the rarer case, the welfare of the child in utero takes precedence of the welfare of the parent; one may conceive that the formative effort for the placenta had been so great that the organism in general was impoverished. As a matter of fact, the bones of the mother are robbed of their earthy matter, and the commencement, at least, of that diversion of substance is somehow connected with the gravid state. It is noteworthy, in this connexion, that a fractured bone in a pregnant woman repairs badly, owing to the deficient production of bony callus. Having once begun, the disease progresses, and the patient dies bedridden; only in rare instances do the bones become hard again. The loss of osseous matter in mollities is accompanied by a return to embryonic characters and function on the part of all the cells that now form the very extensive marrow; the haematoblastic function is conspicuous in the process, and there are also numerous myeloplaxes. Both the unmaking of bone in the parent and the diversion of embryonic tissue from bone-making in the child would appear to be correlated with the haematoblastic function of the cells. In both diseases phosphates are discharged in excess in the urine, and in neither is there any advantage from the excessive formation of blood. In osteomalacia the embryonic state of the marrow changes after a time to a more gelatinous state; sometimes a wall forms round the red pulpy fluid, producing a cyst of the bone with brownish contents, and in these cases the disease is said not to progress farther.

Cretinism.— A much more profound error or defect of all the developmental powers of the body than that of rickets is found in cretinism. Certain aspects of this subject have already been treated of in the articles Cretinism and Insanity ; and another aspect of it is referred to in the section of this article dealing with the thyroid gland (see p. 385). It remains to mention here a few of the anatomical and external characters of the disease. With the low mental development there usually go a large tongue, a broad and flat nose, loose and thick skin, and stunted limbs. The error of growth in the bones, which is only a part of a very extensive range of erroneous development, is somewhat different from that of rickets. In the bones of the skull there is usually found synostosis, or premature union at one suture or another, not unfrequently at the sphenobasilar, giving the base of the skull an up-and-down direction. The premature union along one line or other leads to compensating expansion elsewhere, so that the skull is misshapen; the forehead usually retreats, the top of the head is flat, and the occiput small, the type of skull being markedly brachycephalic or broad. One distinctive point in the bone-lesions of cretinism relates to the stunted limbs, which are not at all characteristic of rickets. The stunted growth depends upon a complete departure from the ordinary relation of the epiphysis to the shaft. A bone such as the thigh-bone grows normally to the length, chiefly by the activity of the cartilage of the epiphysis along the epiphysial line: the cartilage-cells multiply on the surface of the epiphysis next to the shaft; they become grouped in long perpendicular columns; and, as ossification proceeds, the new bone becomes an integral part of the shaft. Meanwhile the epiphysis itself is becoming ossified radially from the centre outwards. In the cretin the activity along the epiphysial line is somehow checked, and it has been found that a fibrous band extending inwards from the periosteum forms a kind of barrier in the position of the proliferating epiphysial line, cutting off the shaft from the epiphysis; thus the shaft is deprived of those accretions at each end upon which its elongation mainly depends. At the same time the cartilaginous epiphysis spends its proliferative force within itself; it expands in all directions, becoming a large knob, and part of its ossification may be effected by a sort of inverted activity of the epiphysial line, which proliferates towards the interior of the epiphysis, instead of growing towards the contiguous shaft. No analysis of these peculiarities of bone-growth in cretins need be attempted, but some remarks are offered on p. 385 with reference to the mother’s share in this congenital condition.

Chlorosis.— Contrasting with rickets, in which the tendency born with the child produces symptoms of ill-health in children of both sexes within the first year, and seldom later than the second, chlorosis is a congenital condition of which there are symptoms first at the age of puberty, and almost exclusively in the female sex. The congenital nature of this condition has been made probable by the anatomical observations of Virchow, which go to show that in chlorotic subjects there is very uniformly found a narrow or inadequate aorta, much more elastic than usual, with its inner coat irregular in thickness and disposed to degenerative changes, and with its intercostal branches coming off in a more than ordinarily irregular manner. These anatomical peculiarities are naturally part of the congenital endowment of the individual. The full force of the chlorotic state is not felt until the time of puberty, and in the male sex it is hardly felt at all. It is, indeed, associated in the most intimate way with the remarkable periodicity of ovulation to which the female sex is subject; it manifests itself in the years when that function begins, and chiefly at each successive period of the function. After a few years the indications of it become feebler and tend to disappear. Want of sunlight in the daily life of the individual is the chief aggravating circumstance of the anaemia of chlorosis. The vascular system is on a small scale, to begin with, and there is too much blood in the body for the size of the vessels; the blood is not quite normally constituted, having too few corpuscles in proportion to the plasma, and in the red disks there is too little haemoglobin or colouring matter. While the blood and blood-vessels are poor, the fat of the body, and especially the subcutaneous, is abundant.

Haemophüia. — This is another general state of the vascular system, which is always congenital, and often runs in families, one or more of whose members are “bleeders.” It is a disorder of the boys of a family just as distinctively as chlorosis is a disorder of the girls. A remarkable disposition to bleed, with or without the provocation of an injury, is the whole disease; neither structural change of the blood-vessels nor peculiar composition of the blood has been made out, and there is nothing remarkable in the ordinary appearance of a bleeder. When the bleeding is spontaneous it comes from the mucous membranes, especially from the nose, but also from the mouth, bowel, and bronchial tubes; one of the most common and fatal traumatic occasions of bleeding is the extraction of a tooth. Even slight bruises are very apt to be followed by extravasations of blood into the tissues; the swollen joints (knee especially) of a bleeder are probably due, in the first instance, to the escape of blood into the joint-cavity or into the synovial membrane. It is always from the very smallest vessels that the blood escapes, and from these it may escape in such quantities as to cause death within a few hours. It appears that the same extensive capillary haemorrhage may occur anywhere in the body provided the opportunity is furnished, by a slight injury or otherwise, for the blood to escape.

§ 6.— Errors of Blood-making in Mature Life.

The words quoted above from Sir William Jenner— “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 precision 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 composition 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-aemia, cholaemia (jaundice), lipaemia (fat in the blood), uraemia, &c., some of which fall to be spoken of in sections 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 important disease called leukaemia.

Leukaemia, or Leucocythaemia.— The relation of the colourless 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 subcutaneous tissue of the faetus, 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 haematoblasts, the red disks being detached portions of the proto- }flasm of the same. There would be in any case several red disks or one surviving nucleus; but in actual blood the proportion of cells of the latter kind is very much smaller than that. The proportion 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 haematoblasts, we must suppose that the protoplasm continues to be renewed around the old nucleus, so that the same haematoblast 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. Evidences that they are so are not wanting in fine sections of these tissues, although the process of budding of the haemoglobin-

tinted fragments of protoplasm is not so marked in all its stages as in those abnormal instances of haematoblastic 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 reddish 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 phenomenon according to the view that they are residual nuclei of haematoblasts, we shall conclude that the haematoblasts have very 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 thaemic disease?

The interest centres in the state of the spleen and of the bone-marrow; according to modem views the so-called lymphatic leucocythaemia belongs to another class of processes and may be here disregarded. The spleen is in all cases enlarged, from twice up to fifty times its normal size; it retains its form, but its structure 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 reddish 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 direction, from which no functional product results (red blood-disks), but mere overgrowth of tissue and of cellular nuclei. The haematoblasts have, in fact, become constructive when they should have continued functional. The enormous number of colourless 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 with 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 appearance of puriform infiltration. Again, the first cases of leucocythaemia 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 leukaemic 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.

Pseudo-leukaemia.— Leucocythaemia 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 haematoblastic function in the spleen or bone-marrow, or in both. There may be a state of leucocytosis without this profound and fatal haematoblastic disorder, wherein the increase of colourless corpuscles is referable to organs and tissues which have no blood-making function. Affections of the lymphatic 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 lymphatic glands and the lymphatic follicles of the mucous membranes 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 thymus; 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 leucocythaemia, and they are better classed under the heading of leucocytosis or pseudo-leucocythaemia. The difference is even discoverable, according to Virchow, in the morphological character of the colourless corpuscles in the two cases. In true leukaemia (splenic) the corpuscles in the blood are somewhat large, with multiple nuclei, and more rarely with a single nucleus; in the pseudo-leukaemia (lymphatic) the cells are small, the nucleus single and large for the cell, the cell - substance being often so narrow a zone as to be hardly appreciable around the nucleus. These are practically the differences between the cells of lymph-glands or follicles and the residual nuclei of haematoblasts (or pus-cells).

This pseudo-leukaemia connects, on the one hand, with Hodgkin's disease, a general condition of lymph-gland overgrowth, and, on the other hand, with solitary lymphomatous tumours, such as grow, mostly perhaps, in children in the kidney, or in the follicular tissue of the intestine, or elsewhere.

Pernicious Anaemia.— This is another serious and generally fatal error of blood-making, which presents both an instructive parallel to leucocythaemia and an instructive contrast. The onset of this disease is often sudden, it may be with symptoms of chills and heats and other febrile manifestations. It occurs at all periods of life, and in both sexes. The body seems to become strangely bloodless, so that even the point of the finger will not bleed if cut. There is much listlessness, often giddiness, tendency to haemorrhages, especially into the retina, and pains in the bones. Recoveries, temporary or permanent, are more usual than in leucocythaemia, especially under the administration of arsenic. The blood is profoundly altered, and the stàte of it may vary much within a space of weeks or even of days. The red disks are enormously reduced in number, and many of those that are left have departed from the usual type; they may be either very large or very small, two or three times larger than usual, or two or three times smaller. Some of them are oval and flat, and some of them pear-shaped vesicles (fig. 41). They may have also an increased colouring power, which means an undue concentration of haemoglobin. When the two chief blood-making tissues are investigated in such cases after death they do not always furnish a rational explanation of the state of the blood. It is, in fact, somewhat rare to find anything elucidative in the state of the spleen, and the interest is thrown mostly upon the bone-marrow. Not always, but very often, this tissue is profoundly altered; even the yellow marrow of the long bones is red or jelly-like, few or no fat-cells are visible, red blood-disks are everywhere, along with granulation-like marrow-cells, in a fine reticulum, and traversed by blood - sinuses which have been compared to the sinuses of the spleen. Sometimes the nuclear cells of the marrow are found with a zone of reddish protoplasm round them or in the state of perfect haematoblasts. In this peculiar disorder of the blood-making process the salient facts appear to be the following. Red disks are formed from haematoblasts with difficulty; they are mostly either much too large or much too small; the haemoglobin is too concentrated in them; the bone-marrow makes quite unusual haematoblastic efforts; but the vessels at large remain ill supplied with blood, while the marrow itself is everywhere full of blood, and sometimes even tends to organize itself into a structure like the spleen. Degeneration follows in the muscular structure of the heart and in the walls of bloodvessels; to the former are owing some prominent symptoms, and probably to the latter the haemorrhages. One of the most singular things in this remarkable disease is the power of recovery, either temporary or permanent, that the organism may acquire, chiefly under the stimulus of arsenic. As compared with leucocythaemia the striking fact is that the part played by the colourless corpuscles is from first to last a subordinate and even unrecognizable one.

Scurvy.— In scurvy we have a blood-disease of a kind somewhat different from leucocythaemia and pernicious anaemia, inasmuch as it depends, not upon unaccountable and seemingly capricious errors in the blood-making tissues, but upon errors in the ingesta, upon well-understood defects of diet. (See Scurvy. ) Irregularities of Blood-distribution.— While the facts of blood-making are among the most fundamental in pathology, the facts of blood-distribution come more visibly into the every-day manifestations of disease. The speed and force with which the blood is driven round its whole circuit vary much; as measured by the pulse at the wrist these conditions of the circulation have at all times been held by practitioners to be of the first importance in diagnostics and prognostics. The local distribution of blood, -or the amount of it within and the rate of its passage through particular organs and parts, is a more recently investigated subject bound up with the doctrine of vaso-motor nerves. One of the most striking facts in this chapter of physiology is the varying amount of blood within the “splanchnic area” from time to time. In pathology the question of the varying distribution of blood comes largely into the doctrine of fever and of inflammation; the further discussion of it is reserved for a later part of the article.

§ 7.— Errors of Secretion.

The pathology of secreting structures is concerned, not only with deviations from their normal activities as described in physiological treatises, but also with an additional series of phenomena recalling the more elementary or embryonic kinds of cellular activity. Besides those great disorders of glandular structure and function which fall to be considered in the next section as errors of metabolism, there is a large part of the sum-total of disease which is merely an affair of elementary cellular irregularities in the mucous surfaces and glandular organs of the respiratory, digestive, and reproductive systems. In the foregoing illustrations of pathological processes it has often occurred to notice the obtrusion, as it were, of earlier phases of cellular activity into later life, or the revival of embryonic characteristics, both structural and functional. The illustrations already given have related chiefly to blood-making and bone-making; we now come to a corresponding class of illustrations from the epitheliated parts of the body. In the latter also there is a liability to revert to rudimentary forms of cell-life, wherein the epithelial cells reveal their inherent power to act as independent units, or their spontaneity and their self-governing properties. Thus, among the morbid conditions of the respiratory apparatus there are only a few, such as asphyxia, the Cheyne-and-Stokes breathing, and the like, which are directly in contact with the physiology of the respiratory mechanisms. On the other hand, pulmonary catarrhs and their structural after-effects (together with laryngeal and tracheal inflammations) enter largely into the pathology of the respiratory organs, although they are hardly deviations from those respiratory functions that have the engrossing interest for physiology. There is the same class of elementary cellular deviations among the morbid states of the digestive organs, and, most of all, in the pathology of the genito-urinary system,—of the uterus, bladder, and prostate,—and of the breasts. The most universal error that epitheliated surfaces or organs are liable to is catarrh; and closely related to their liability to catarrh is their liability to polypous and simple-glandular tumours, and, under special circumstances, to cancer.

Catarrh in general.— The term catarrh {κατά, down; ρlω, flow) was originally applied to a running from the nose; the mucus was called “pituita,” and in the Hippocratic doctrine of the humours it was exalted to a place side by side with the blood and the bile. The vague importance assigned to this humour in the medical philosophy of the Greeks is further shown in the curious fiction which made it to issue from the hypophysis cerebri or “pituitary” body. The mucus of the nose may stand for the mucus of the airpassages generally, and it differs only in degree from that which is expectorated when there is considerable bronchial catarrh. It is now usual, and the usage is scientifically justified, to include all other mucous or muco-purulent or purulent discharges from epitheliated surfaces as the result of a “catarrhal” process.

Those mucous surfaces that are most liable to catarrh are ordinarily kept moist by an exhalation or secretion; in the mucous membrane of the stomach and intestine the surface-moisture amounts to a definite layer of glairy or tenacious mucus. In some of the mucous membranes, such as those of the pharynx and oesophagus, trachea and bronchi, there are distinct racemose glands which appear to subserve solely the purpose of lubricating or keeping moist. In every case the normal mucus of an epithelial surface may be taken to be a product of the epithelial cells; it is as if it were a common and rudimentary function of surface-epithelium anterior to the specific secretions of organs. It is in this common and rudimentary function that the catarrhal process has its roots, a process which not only exceeds the physiological limits of surface-moisture, but may even throw into the shade the specific secretion of the part or organ. The catarrhal secretionis always characterized by the large preponderance of cells, and the proportion of cellular elements increases as the mucous substance becomes muco-purulent and purulent. It is important to observe that there is no definite line where the limits of normal moistness end and “inflammation” begins; and, as it is desirable to put off as long as possible the introduction of that entity into pathology, we shall best proceed in the study of catarrh by advancing from the physiological activities of cells.

Nature of the Catarrhal Process.— The catarrhal process, like all the so-called inflammatory processes, has been rendered ambiguous by the undoubted share in it that is taken by hyperaemia or afflux of blood to the particular epithelial region. By some the hyperaemia has been taken to be the primary fact, the increased rush of blood to the part and the local stagnation of the same being traced to an upset of the controlling and equalising nervous mechanism of the vessels and to alteration of their walls; by others the local cellular process has been regarded as determining the afflux of blood, as if by a kind of attraction. Whether the afflux of blood precedes the unusual activity of the epithelial cells, and whether some of the catarrhal cells may not be emigrated colourless corpuscleá, are questions that may be considered open; but there can be no question that catarrh is essentially a hypersecretion of the epithelium, or the secretory activity so modified that it becomes to a great extent formative, or its product to a great extent cellular. The difficulty of proving this is owing to the fact that the normal production of mucus from epithelium is a very subtle and rapid process, the morphological phases of which are hardly to be detected; in this respect it must be considered analogous to the formation of red blood-disks from haematoblasts. And, as the details of the haematoblastic process are best seen in certain abnormal manifestations of it, and even in those cases where the morbid condition is one of anaemia, so the complete physiological paradigm of mucus-production is best seen where there has been some interference with the perfection of function. We shall perhaps not go wide of the mark if we describe the catarrhal process as a reversion to a more embryonic or more elementary type of cellular activity. The higher the type of secretion, the less obvious are the morphological changes in the secreting cell; in an organ like the liver, which had been early acquired in the evolution of the animal body, the secretion has become so elaborated in the higher animals that the steps of it present hardly any morphological features at all; on the other hand, in an organ like the breast, which is a late (mammalian) acquisition, the changes in the secreting cell can be followed at leisure. Catarrh in any mucous surface is the same primitive kind of secretion, and it may be said, in a word, to consist of a fluid product and of an additional by-product of cells. The original epithelial cell is detached bodily, nucleus and all; the protoplasm becomes the more or less viscid or semifluid part of the mucus; and the nucleus goes with it as the catarrhal cell. The more the cellular elements predominate, the farther does the secretion deviate from the normal, until we reach the limit of pus, where we invoke the entity of “inflammation.”

Succulence and Thickening of the Catarrhal Mucous Membrane.— A mucous membrane which has been the subject of catarrh for some considerable time becomes thicker and more succulent. If it be examined in microscopic sections it will be found that the underlying connective tissue has become involved; the tissue is “infiltrated’’with round nuclear cells (fig. 42); the fibres are becoming thicker; and the fineness, delicacy, and translucency of the tissue are disappearing. At certain spots where the “infiltration” and associated changes are greatest the surface breaks or ulcerates, and a “catarrhal ulcer” remains. The central fact in this process is the infiltration of the round nuclear cells beneath the epithelial surface. The facile way of accounting for them is to assume that the colourless corpuscles of the blood had escaped through the walls of the small veins; but it is more in accordance with observed facts and with unambiguous analogies to regard them as catarrhal cells which have found their way into the depths of the tissue instead of flowing oft’ by the surface. The presence of these cells in the spaces of the connective tissue is not without effect on that tissue itself; they rouse it to a formative activity which conducts to the succulence and thickening of the mucous membrane, and, it may be, to ulceration at particular spots. To enter on this subject at present would be to open up the question of the infective action of one kind of cell upon cells of another kind (see pp. 382, 383).

Physiological Analogies of Catarrhal Infiltration.— The infiltration of catarrhal cells beneath the mucous surface has close analogies in the normal processes of the body. It is exactly paralleled in one of those crude forms of secretion to which the catarrhal process has been compared, namely, the kind of secretion, gradually rising in intensity, which goes on in the breast during the period ' of gestation. This process can be most conveniently observed in the mamma of the cat or dog, where the crude secretory products are for a time cells of considerable size filled with yellow or brown pigment; the pigmented cells can be followed from the secreting structure into the spaces of the surrounding connective tissue, and thence into lymphatic glands. It would not be carrying this analogy too far to regard the lymphatic follicles of the mucous membranes as collections of or receptacles for the cellular by-products of the mucous secretion; such are the tonsils, the follicles on the back of the tongue and pharynx, the lymphatic follicles of the stomach of some animals (but not of man, unless it be in infancy), the extensive stratum of lymphoid cells in the villi of the small intestine and the more definite collections of the same (Peyer’s patches), and the lymphatic follicles of the great intestine.

Certain it is that all these collections of round nuclear cells are subject to very considerable increase when there is catarrh in the corresponding mucous surface. Not only so, but in catarrh they will show themselves prominentlyeven where they are hardly known to exist normally; thus, in the intestinal catarrh (summer diarrhoea) of young children, even the thin folds of the mucous membrane (valvulae conniventes) will be found studded with round nodular or somewhat flattened lymphatic follicles. In intense catarrh these follicles are the favourite seats of ulceration, their substance changing into a “follicular ulcer.” In other cases the catarrhal process makes its influence felt in the nearest lymphatic glands, which may be regarded as the second line of receptacles for the by-products of secretion (as well as for the matters of absorption), the submucous follicles being the first line; and, under these circumstances, the lymphatic glands may even suppurate (as in the axillary lymph-glands of the breast after weaning).

Tumour-diseases of Mucous Membranes and of Secreting Structures generally.— If catarrh of mucous membranes enters, as Rindfleisch says, into the larger half of all the morbid conditions to which mankind is subject, the tumour-diseases of the epitheliated surfaces and organs may be said to rank among the most formidable of all maladies, inasmuch as they include cancer. Cancers are diseases primarily of mucous membranes and other secreting structures, most commonly of the stomach, next to it of the uterus, of the female breast, and of the intestine; another variety of cancers (epithelioma) is diseases of modified epithelial surfaces, namely, the skin in general, and the lip and tongue. There are, however, much simpler tumour-disorders of epitheliated surfaces which it will be convenient to take first.

Warts (Papillomata). — Papillomata of the moist epitheliated surfaces are found almost exclusively in those situations where there is a transition from skin to mucous membrane. The rule may not be universal, but there are many instances in which these wart-like growths have an undoubted relation to a catarrhal process of the surface, where the removal of the catarrhal products has been interfered with. One of the most striking illustrations of this law occurs in veterinary practice; in the horse, especially when he is overworked and ill cared for, the natural smegma of the prepuce gets retained, owing to the fixity of the sheath; the accumulation has more than a mechanical effect, for it appears to induce a papillomatous condition sometimes of the whole mucous surface. The papillomata are new growths, either in a broad layer of the uniform thickness of a quarter of an inch or more, or they are large dendriform masses arising at various points and each attached by a narrow stem. It is hardly a catarrhal process that we have here to deal with, but it is none the less a disorder of secretion. The natural secretion not finding an outlet, the secreting surface adapts itself gradually to the unusual conditions. The surface becomes ridged or thrown into folds, or papillae arise at isolated points; blood-vessels run in the central parts of all these reduplications of the membrane; and the epithelium, instead of disengaging itself in successive generations of cells after the manner of the natural smegma, takes on a formative activity and builds up an adventitious tissue on the surface, the pattern of which is determined by the looping or dendriform branching of the bloodvessels (fig. 43). These formative aberrations of secretion are apt to return after removal, even although the conditions which gave rise to them are obviated; the new development and persistence of the bloodvessels entering their stems appear to be the occasion of recurrence in these cases.

Mucous Polypi.— In many cases mucous polypi have an undoubted connexion with those states of the mucous membranes which are included under catarrh. An approximation to a multiple polypous condition may be found in the stomach subject to longstanding catarrh, where the ridges and furrows of the mucous membrane amount to an actual polyposis ventriculi. Multiple polypi are sometimes met with also in the intestine. The commonest seats of the isolated and stalked mucous polypus are the nasal passages and the cervix uteri. Their structure is after the same plan as the more epidermic papilloma, everywhere tubular mucous glands, the epithelium of which is wonderfully perfect (fig. 44); these may branch or communicate more than do the normal glandtubes of the part, and they are separated by tracts of connective tissue which appear to the naked eye as dendriform white lines. In these morbid products the line is definitely crossed from functional to formative, but we cannot assume any other force than the indwelling secretory activity of the part; the unique fact that presents itself here is that a perversion of that force gives rise to an organ-like new formation whose plan of structure is plainly determined by the blood-vessels. It is worthy of note that the bronchial mucous membrane, which is the most liable to catarrhs, has practically no liability to mucous polypi; and the bronchial mucosa is distinguished, not only by its investment of cartilaginous rings and plates, but by the density of its elastic and muscular coats.

Simple Glandular Tumour (Adenoma).— As the mucous polypus • is characteristic of the wide expanse of mucous membrane, so the simple glandular tumour or adenoma is the formative result of functional disorder in the definitely bounded epithelial organs with racemose systems of ducts. The glands that are most liable to this condition are the breast, the salivary glands (including the buccal and labial), the lacrymal glands, and the skin-glands in certain regions. Whenever the more uniform expanses of glandular structure, such as those of the stomach and the intestine, take on a formative activity to the depth (instead of to the surface, in the form of polypi), the result is a cancer, involving other considerations besides those primary or direct deviations from the secreting activity which we are now considering.

Intra-canalicular Papilloma.— The simple or non - cancerous tumour-disease of glands may be represented in most cases in the light of deviations from the normal secretory activity,—deviations which take a formative direction. They connect not remotely with catarrhal states of the secreting structure; but, speaking generally, they stand for irregularities of the apparatus and process of secretion which transcend the notion of catarrh. It will be convenient, however, to proceed in the analysis of them from that familiar basis. The nearest approach to the effects of catarrh is shown in the folded or uneven state of the wall of the terminal secreting recesses or acini of a gland; this condition may be observed in certain skin-glands and in the breast. The cut (fig. 45) is taken from a tumour of the skin-glands of the dog. The lining of columnar or cubical epithelial cells, which is ordinarily a perfectly even surface, is raised into distinct papillary eminences. These may even meet across the space, changing its interior into a nearly solid or at least trabecular tissue. The next cut (fig. 46) shows precisely the same process in the breast, this time not in an acinus but in a duct; the result is what is called an “intra-canalicular papilloma,” and it is not different in its origin and nature from the papillomata of expanded mucous surfaces which we have already considered.

Cartilaginous Tumours of Glands.— Another formative result of 1 disordered function, which takes us quite beyond the limits of < catarrhal effects, is the occupation of the walls and interior of the; acinus, not with papillae of the lining epithelium nor with the 1 epithelial cells shed into the free space as solid by-products oft the secretion, but with a new tissue foreign to the gland. This < occurs in the mamma (more often in the dog than in man), in the < salivary glands (parotid, submaxillary, and labial), in the lacrymal gland, and in skin-glands (e.g., of the scalp); the new tissue may be of the mucous or myxomatous kind, and it is not rarely cartilaginous, or even osseous, at a few points in the midst of the cartilage. The occurrence of myxomatous and cartilaginous areas is common in the parotid tumours of man and in the mammary tumours of the dog, and it is usually explained as an arbitrary and unaccountable overgrowth and transformation of the supporting connective tissue of those organs. It remains to inquire whether it may not be brought into a rational connexion with disorder of the proper secretory function. The cut (fig. 47) is taken from a case of extensive tumour-disease in the mamma of the bitch, in which much cartilage had formed. It represents several acini of the gland, having their interior occupied with large spherical or oval vesicu-

lated cells with firm hyaline contents. There can be no question that these are epithelial cells strangely changed; but the change will not seem so strange if we keep in mind the range of transformation which the secreting cells of the breast are normally liable to. There is a stage in the unfolding of this gland from its periodical state of rest in which the cells become vesicles filled with mucus, just as there is a more mature period when they are still vesicles but filled with a more fatty or milk-like fluid. The change in the tumour is, after all, only from the mucus-filled vesicles to vesicles occupied by a firm hyaline substance; and, if it were connective - tissue cells that we were dealing with, the explanation would be at once accepted, according to the well-known correlation between fat, myxomatous tissue, and cartilage. The facts seem to require that the same formative possibilities be granted to epithelial cells; so that the myxomatous and cartilaginous formations in secreting structures would be traced to their active elements. The supporting tissue of the glands is a priori passive, and, as a matter of fact, it has not been proved by any detailed observations to be the source of those myxomatous and cartilaginous new formations. The occurrence of vesiculated epithelial cells with firm hyaline contents is not the only piece of positive evidence. It is much more common to find the columnar epithelial cells elongating into fibre-like elements, straight or crescentic, and developing mucous or hyaline intervals of intercellular substance; in this way there results the myxomatous and fibro-cartilaginous tissue that is so often found in the tumourdisorders of the salivary glands and more rarely in the labial mucous glands. The glandular plan of the structure in these cases very soon becomes obliterated, and the limits betwéen supporting tissue and secreting apparatus removed; in a considerable area of hyaline cartilage or fibro-cartilage there are naturally few or no traces left of the apparatus and process of secretion; and there may some times be seen (as in the mamma of the bitch) the most remarkable development of all, the change of the cartilage into bone, with perfect medullary spaces lined by perfect osteoblasts. There are, indeed, no limits, other than the fundamental embryological limits, to the formative possibilities of cells which have reverted to primitive embryological function. We have already seen that the standing example of an embryonic tissue, the spindle-celled tissue of the ovary, contains within itself the whole range of development which is expressed in the grotesque variety of a dermoid cyst.

Another common effect of disordered glandular function is the excessive formation of solid by-products of the secretion, which are either retained in the recesses of the gland or are infiltrated into the spaces of the underlying and supporting connective tissue. Where the products are retained within the gland-space we have the familiar and simple result of cysts from retention, of which the sebaceous cysts or “wens” of the scalp are good examples. But a far more momentous occurrence is the infiltration of these cι ’ ude products or by-products of secretion into the depth. We have already found reason to believe that the same kind of infiltration below the surface takes place in catarrhs, that the nuclear cells found in the deeper layers of a thickened mucous membrane are of the same origin as the catarrhal cells of the surface-discharge, and that their presence in the spaces of the connective tissue had been the exciting causé of the fibres becoming thick and coarse, or, in other words, of the “inflammatory” changes in that tissue. The infiltration which comes under our notice in tumours of secreting structures is different from this as regards the characters and properties of the cells: as regards their characters, the cells retain more of the epithelial type, that is to say, they are not naked nuclei, but they have a considerable investment of cell-substance; as regards their properties, these epithelial cells infiltrated below the mucosa do not excite “inflammation,” but they excite cancer. What remains to be said of the infiltration of by-products of glandular secretion will be included in the section on cancer immediately following.

§ 8.— Cancer.

The popular estimate of the nature of cancer is so well founded that a definition is superfluous. Cancer in pathological anatomy differs from cancer as commonly understood in being restricted to the malignant tumour-diseases of secreting structures and epitheliated surfaces generally, to the exclusion of a certain number of equally malignant tumours which grow from the periosteum or the marrow of bone, or from other mesoblastic tissues. The great majority of all the cases which have the fatal progressiveness of cancer are diseases of the stomach, the uterus, the breast, the intestine, and the skin; this group makes so large an element in the sum-total of tumour-disease, and is so homogeneous within itself, that it may justly appropriate the name of cancer, leaving the other cases of tumour-malignancy to be described by· more technical names. At the same time it should be clearly understood that the smaller detached group does contain cases where the particular manner of fatal progression is not different from the progressiveness of the epithelial tumour-disorder, such, for example, as the cases of periosteal tumours becoming parosteal.

Chief Seats of Cancer.— The absolute and relative frequency of cancer in the various seats of secretion has been ascertained by D’Espine, from the mortality returns of the canton of Geneva, for both hospital patients and the well-to-do treated at home, to be as follows over the period from 1838 to 1855 :— [table]

being 762 or 85 - 3 per cent in a total of 889 cases of malignant tumours of all sorts. Most cases of cancer of the liver are really secondary to canecrs in the stomach or elsewhere, so that the leading position of the stomach, and after it of the uterus, the breast, and the intestine, becomes more marked. According to the facts collected by Virchow from the mortality returns of the town of Würzburg from 1852 to 1855, the deaths from malignant tumours were 5 - 3 per cent, of the total mortality, and the percentages among malignant tumours were as follows :— [table]

It may be accepted, then, that the digestive tract is the seat in about one-half of the cases of malignant tumour-disease, and the female sexual organs (excluding the ovaries, but including the breasts) in about one-fourth, while the remaining fourth has to be apportioned among other epithelial organs or parts and the bones and other mesoblastic tissues. It must not be supposed that these ratios hold good equally for all localities; the breast sometimes appears to usurp a larger share, and sometimes the rectum. Again it is a noteworthy fact that cancer is a comparatively rare disease among the vast populations within the tropics.

The beginnings of cancer have to bo sought for in disturbances of the apparatus and process of secretion. Even in the cases where hereditary or congenital predisposition plays a part there must have been local irregularities of structure and function to determine the seat of the disease; thus, of four sisters of whom three were married and had families, one died of cancer of the breast, another of cancer of the stomach, a third of cancer of the rectum, and the fourth of cancer of the uterus,—the incidence of the disease in them all happening about the age of fifty to sixty. Cancer in secreting structures is essentially one process; but each of the • favourite seats of cancer has its own special liability, as well as points of structure special to itself. The liability of the female breast is an entirely different thing from the liability of the stomach; and the liability of the uterus is more closely allied to that of the stomach than to that of the breast, although the breast and the uterus have a closer systemic relationship. There is, however, something in the cellular law of secretion common to them all, and it is that common feature of the secretory process which first engages the attention.

Relation of Cancer to Secretory Process.— The product of secretion is not, under all circumstances, a fluid; in the simpler forms of animal life, and in more recent or less elaborated glands of the higher forms, it may be thrown off in cellular shape, just as it is always cellular in its origin. We have already seen that in the catarrhal state the cellular admixture is considerable, and there can be hardly any question that the cells of a catarrhal discharge are derivatives of the epithelial cells, being indeed little other than their nuclei. We have also seen reason to believe that the infiltration of nuclear cells in the thickened mucous membrane of chronic catarrh had been a real infiltration of the catarrhal cells beneath the surface. Now the favourite seats of chronic catarrh, the stomach and the uterus, are also the favourite seats of cancer. What, then, is the relation between these two very different diseases, both of them primarily disorders of the apparatus and process of secretion?

A particular case will bring out the points of resemblance and the points of difference. In a fatal case of cancer of the stomach the whole organ is found to be uniformly thickened, the mucous membrane being much ridged and furrowed; but its epithelium is unbroken. The interval of submucous tissue, ordinarily a loose layer between the mucosa and the muscular coats, is occupied throughout the whole extent of the organ by a nearly uniform stratum of firm whitish tissue. This is an exceptional case of cancer of the stomach, but it is a very instructive one; the morbid condition is as uniformly diffused over the organ as if it had been the thickening of chronic catarrh, and it wants the usual tumour - character of cancer.

The microscopic examination proves, what the whiteness and almost gristly firmness of the submucous interval had suggested, that the disease is hard cancer. The white stratum under the mucosa has the structure shown in the cut (fig. 48), and it is an average example of the infiltration of scirrhous cancer. Epithelial - like cells, with a disproportionately large nucleus, are as if packed in rows in the spaces of a very dense fibrous tissue, which contains a large number of elastic fibres. Besides the linear processions of celts, there are elsewhere groups of them arranged round the walls of spaces like the epithelium of a gland. Throughout the whole thickness of the coats of the stomach in this case such collections of cells are found; in the muscular coats they are met with chiefly where there are fibrous septa; and it is noteworthy that the glandlike collections are by far the most numerous in the tissue most remote from the physiological glandular surface, namely, the connective tissue of the serous or external coat (fig. 49). It is impossible to trace a continuous growth of these subserous glandlike groups of cells from the actual glands of the mucous surface; they are separated from the latter by nearly a quarter of an inch of muscular and other tissue, in which the “infiltration” occurs only here and there. The wide extension of the cancerous process is not mere overgrowth or protrusion of the secreting structure, nor is it even an infiltration, in the literal sense, of the cast-off secreting cells; it is an infection of the cells of the subjacent tissue to become epithelial cells and gland-like cell-groups.

And therein lies the essence of cancer.

Extension of Cancer from the Sτιrface to the Depth.— Whereas, under commoner circumstances, the catarrhal by-products of the process of secretion find their way to the underlying textures and there give occasion to an “inflammatory” reaction, to hardness and coarseness of the connective tissue, under other circumstances the less nuclear or more epithelial by-products of the glandular activity have the power to induce the remarkable formative process in the neighbouring tissues which we know as cancer. The cancerous process implies, accordingly, such a condition of the secreting structure and function, or of its individual cells, as can excite this formative reaction, and it involves also the changing of the surrounding tissue (or of its cells) into epithelial forms of cells, either in rows or groups or in gland-like systems. As regards the former, there is no lack of evidence that cellular by-products of secretion are often the antecedent or concomitant of cancer in an epithelial organ or part; they may be seen sometimes in the stomach heaped up between the glandular tubules, or in the mammary gland (especially of the bitch) infiltrated into the surrounding stroma. The cut (fig. 50) is an illustration from the mamma; the rows of cells which lie in the spaces of the connective tissue are the cellular products of the secretory function characteristic of an immature or low-powered intensity of secretion, and they are easily identified in all phases of the mammary secretion in the dog, whether regular or irregular, by their yellowish - brown pigmentation. It is not to be expected that such an infiltration of by-products of secretion can be proved for every case of cancer, nor is there reason to suppose that there is always such an infiltration. The elements of the secreting structure may serve in situ to excite or infect the neighbouring tissue, and this they usually do for the connective tissue on which they immediately rest. But we have to take due account of the much more important fact that the infection also manifests itself at a number of remote and isolated centres, within each of which the new growth arranges itself as if implicitly according to a design, the pattern being the more or less regular epithelial type proper to the organ or part. Thus in fig· 49, from a diffuse cancer of the whole stomach, the glandular tube-like structures have arisen at a number of points in the connective tissue of the outer coat. The pattern of tubular glands is often more complex than in that figure, both in other stomach cases and in cancers of the great intestine and rectum. This remarkable breaking out, as it were, of very perfect epithelial tubules, disconnected from the physiological tubules and often in the midst of dense tracts of plain muscular fibre, appeared to Johannes Midler to be so extraordinary that he ascι - ibed them to an invisible seminium dispersed through the tissues; according to him, the seminium was a literal seed whose particles themselves grew to be the new epithelial cells. We do not now admit the possibility of cells so arising by generatio equiυoca ; every cell must be the descendant of some pre-existing cell. And, although it is necessary to retain the doctrine of the seminium, the part played by that hypothetical element is not formative within its own particles; but it is a fertilizing or infecting influence upon the pre-existing cells of the neighbourhood. In most cases the cells so fertilized are the corpuscular elements of the common binding-tissue of the body, or the connective-tissue cells.

Cancerous Infection of the Connective-tissue Cells.— The cut (fig. 51) is an exact drawing of a piece of cancerous tumour where the connective-tissue cells can be seen in the act of transforming into epithelial cells, or in various stages of that t ransformation-process. The process carries us once more back to that embryonic activity of cells in mature life which we have had frequently occasion to discover in other elementary processes of disease. The cells of the connective tissue are ordinarily quiescent in the form of plates more or less compressed laterally, the cell-plates of tendon being extreme examples. Just as, in the process of repair, they become plump and granular, developing in the third dimension as well, and ultimately becoming granulation-cells, so in cancerous infection they start from their obscurity among the bundles of fibres, passing by rapid transitions into the form and semblance of the epithelial cells proper to the occasion; and they may even go on to assume a glandular grouping round the wall of a space, acting as if harmoniously or according to an implicit design. There is no fact in pathology more noteworthy than this; if it has any analogy among the facts of normal biological processes, we shall probably have to go to the very lowest groups of animals or to the earliest stages of evolution to find it. Whatever the infective influence may have been, it touches all the quiescent cells over a certain area simultaneously; a “territory” of tissue, larger or smaller as the case may be, but always involving a number of cells, assumes the embryonic life throughout its whole extent, and goes through all the steps of the transformation towards the epithelial type and grouping, as if its cells had received one common impact.

States of the Connective Tissue predisposing to Infection.— There are, indeed, reasons for thinking that the special factor in the production of cancer, and of the production of it at particular spots in a large area of choice, is not so much the presence of cellular by-products of the secretion as a particular disposition of the connective tissue of the particular spot to be easily acted on by them. Catarrhal products are often present without any infection following; but the two favourite seats of repeated or chronic catarrh, namely the stomach and the uterus, may at length become the seats of cancer. Cancer is hardly ever a disease of the first half of life; it is very distinctively a disease apt to occur after the meridian is passed. In those who are liable to uterine and gastric catarrhs the mucosa and the submucosa at length become thick and succulent. This happens at particular spots, notably just within the pylorus of the stomach; the epithelial surface may not be appreciably different from the surface elsewhere, but the underlying tissues are thickened and, it may be, contracted to a stricture. It is in such dense new formations of connective tissue that cancer is most apt to form; what is called cicatricial tissue is proverbially liable to cancer, and a tissue may be to all intents and purposes “cicatricial” (and apt to shrink) even if it underlie an unbroken surface. Some cancers of the stomach form entirely below the surface, in the thickened floor of a healed ulcer, or even in the not unfrequent dense adhesions between the serous membrane of the back of the stomach and the piece of peritoneum which is drawn over the anterior surface of the pancreas. A cancerous stricture of the intestine or rectum is not unlikely to have been to some extent a stricture before it became a cancer. The condition of the connective tissue in all such circumstances is not easy to define; it is often spoken of as young connective tissue or “embryonic,” and there is probably in it a smaller preponderance of the fibrous element over the cellular than is usual in mature life. A general change in the connective tissue of the body has been asserted to take place as age advances, a senile change which has been described by Thiersch, for the corium, as a relaxed state. The epitheliated localities subject to persistent functional disturbance do at least seem to undergo a change in their underlying or surrounding connective tissue, whereby that tissue becomes predisposed to cancerous infection. The infection emanates from the secreting structure proper, for it carries with it the likeness of such structure (in its more or less irregular or morbid state). The cellular waste or byproducts of the secretion would appear to acquire something of the property of sperm-cells; and, inasmuch as the infected or impregnated connective tissue produces not merely individual epithelial cells of the appropriate type but also the appropriate grouping of such cells, the sperm-cells must be held to carry more than the influence of cell-units, and in fact to be representative of the whole structural and functional process in which they had played a part Varieties of Cancer.— The two main varieties of cancerous texture are the hard and the soft, or the scirrhous and the medullary.

I Scirrhous cancer is very often the “infiltrating” kind, with the epithelial cells lying in scattered groups or in single file within the spaces of a peculiarly dense and elastic connective tissue. It is common in the breast and not rare in the stomach. The medullary cancer consists of very much larger and closer groups of cells, which may be in nondescript heaps or in the more regular arrangement of glandular structure. When the glandular type is very distinct the tumour is sometimes called a “destructive adenoma.” Colloid cancer is a very peculiar variety, apt to occur in the stomach but not unknown in the breast; most of the structure is changed into a brownish jelly - like substance which forms more or less definite spherical or alveolar masses separated by narrow bands of stroma.

Under the microscope (fig. 52) little of cellular structure of any kind is found remaining, but in place of it there are an immense number of spherical pearl-like bodies, each of which consists of several delicate concentric laminae arranged round a more dense nuclear point.

Cancer of the skin, and of the lips and tongue, is generally termed epithelioma ; it is not a disorder of secretion in the same sense as other cancers are, but it is a disorder incidental to the constant waste and repair of the epithelium of the skin. It is characterized by the encroachment of processes of the rete mucosum upon the corium and subcutaneous tissues, or, in the 1ips, tongue, upper part of the oesophagus, &c., of epithelial columns of cells upon the subepithelial region. The type of this encroachment is the papillary arrangement of the normal rete mucosum, where the appearance of regular columns of epithelium reaching down into the corium is equally due to the reciprocal protrusion of loops of blood-vessels upwards. The interlocking of epithelial -columns and connective-tissue tracts in epithelioma is much more extensive and irregular than in the normal skin, and it is always difficult to decide, from the superficial microscopic appearances, whether the encroachment of the epithelium is merely a displacing or a transforming encroachment (fig. 53). In some cases, such as destructive epitheliomas of the tongue, or of chimney-sweep’s cancer, it is possible to find reliable evidence in the microscopic sections that the progressiveness of the disease is really an infection, like that of cancer elsewhere— that is to say, the neighbouring tissues, and more especially the connective-tissue cells, are infected so that they assume the epithelial type proper to the locality—and that infection tends to spread without limit. But the doctrine of continuous growth from the rete mucosum downwards, by mere subdivision of pre-existing epithelium, appears to be justified as a part, at least, of the pathology of cancer of the skin. As in cancers of the stomach and uterus, the regions liable to skin-cancer are especially those subject to repeated irritation or to prolonged functional disturbance. One of the most striking instances of this law used to be the cancer of the skin of the scrotum and groins in chimney-sweeps, a form of disease which has become much less common of late. Again, it is nearly always the lower of the two lips that suffers, and the rare cases of epithelioma of the lip that occur in women are among those of the sex who smoke pipes. Like other cancers, the cancer of the skin, lips, and tongue, &c·, is a disease of later life; according to Thiersch, it is due to a “disturbance of the histogenetic equilibrium between epithelium and stroma, to the disadvantage of the stroma.” The perfect balance of tissues would be exemplified by that regular interlocking of vascular papillae from below and epithelial processes from above which the skin ordinarily shows; as age advances the downward force of the epithelial growth prevails, owing to a certain decreased “turgor vitalis,” or to loss of resistance on the part of the tissue carrying the blood-vessels, so that, when long-standing irritation of a particular spot is added, we should have the two great determining causes of cancer of the skin. But the question will always remain, whether the essence of the disease is not really an infective transformation of the quiescent cells of the connective tissue into the type and pattern of the irritated epithelial structure.

The female breast is peculiar among the glands of the body in its great liability to cancer; the disease is of essentially the same nature as that which we find in the stomach and other epitheliated organs, but the occasion of it is quite different. It will therefore be convenient to reserve further remarks on cancer of the female breast until the next section—thatonthe “liabilities of obsolescence.”

Extension of Cancer to Lymphatic Glands and other Discontinuous Parts.— If the beginnings of cancer are to be sought for in some disorder of the apparatus and process of secretion, the disease very soon passes the limits of the primarily disordered organ or part. The cancerous property of a tumour, as we have concluded, is from the first an affair of infection of the neighbouring tissues by epithelial products; the infected neighbourhood is the seat of the primary tumour, the progressiveness or infiltrating character of which may soon cause a large area to be involved and a large growth to result. Sooner or later there is discontinuous infection, or the infection of more or less remote centres, whereby secondary tumours arise. This phase of cancerous infectiveness is by no means dependent on the extent of the primary infection or the infection of the original neighbourhood. That which distinguishes secondary cancerous nodules,-wherever they are found, is the very close mimicry of the pattern of structure in the indigenous seat of disease, a pattern which is itself deteπnined by the structural and functional characters of the secreting organ or part concerned. In the majority of cases the nearest lymphatic glands become the subject of this mimetic process first; the liver also is very liable to discontinuous infection, not only in cancers of the stomach and intestine, but even in cases of cancer of the breast, submaxillary glands, &c. There is always an interval of time before this secondary infection is set up; and, although the cellular process is not different in kind from the infection of the neighbourhood of the indigenous disease, it is necessary to regard the latter as, in a sense, the parent of the former. This parental relationship is made all the more probable by the fact that sarcomatous tumours, which depend in many cases upon a reversion to or survival of embryonic characters in the mesoblastic cells of a particular locality, are also apt to be followed by tumours in distant parts, particularly in the lungs. In cancers, accordingly, we should distinguish three factors, and in sarcomas only two: in the former we have first the accumulation of cellular by-products of the secretion, next the infection of the predisposed connective tissue by these epithelial products, and lastly the parental influence of the whole primary seat of infection; in the latter we have the embryonic reversion of cells over a particular region, together with their increase or growth, and then the parental influence of the tumour which had so arisen. In both cases the primary tumour acquires a kind of individuality and a power to reproduce itself; but it is only in some cases of sarcoma, especially those soft tumours of periosteal origin which become parosteal, that there is infection of the neighbourhood, whereas a cancer is not a cancer at all until the tissues adjoining or supporting the epithelial secreting structure are epithelially infected. This difference between sarcoma and cancer corresponds to the familiar fact that the former are only occasionally “infiltrating” tumours, being in most cases marked off from the neighbouring tissues by a definite capsule.

The simplest case of discontinuous cancerous infection is in the lymphatic glands near the original seat of disease. It is only exceptionally that the lymphatic glands are infected in sarcomatous tumours, and those cases appear to be mostly the infiltrating sarcomas which have the distinctively cancerous property of infecting the neighbourhood. Infection of the axillary lymphatic glands is the common sequel of cancer of the breast, while the epigastric, portal, mesenteric, and other abdominal lymph-glands receive the infection in cancer of the stomach and intestine. In epithelioma of the lip and tongue the infection of lymph-glands is much slower, and is often so slight as to be undetected during life; it specially affects the lymph-glands under the chin. In all cases the tendency is to reproduce the exact pattern of the primary tumour. In some, including those sarcomatous cases where this kind of infection does take place, the lymph-gland seems to have been transformed en masse, very rapidly and directly, so that steps in the process aro hardly to be detected. But in other cases it is possible to find, either within the same gland or among the various glands of a cluster, a certain amount of instructive histogenetic detail as to the mode of infection. The lymphoid cells become affected, not certainly in the way of atrophy, but in the way of transformation. There is indeed nothing more wonderful in the whole range of biological phenomena than to observe the adaptation of the cells and tissues of a lymph-gland to assume the cancerous structure already established in the organ to which they are related, an adaptation always close in its mimicry, involving the co-operation of large groups of cells and fibres, and directed as if by a presiding intelligence. In many instances the infecting substance may even want the perfect cellular character; it may be no more than the detritus or the juices of cells and tissues. The most obvious form of infection, although probably the rarest, is where the new growth extends continuously along the sides or in the interior of lymphatic vessels from the secreting structure to the lymph-gland; but even this continuous extension has been shown to be, not a protrusion of the primary tumour by increase or subdivision of its elements, but a succession of infective transformations along the line of cells constituting the lymph-vessel or investing it. Under all circumstances the lymph-gland becomes changed ultimately into a texture which reproduces with astonishing fidelity the particular pattern of the primary cancer, a pattern which is never quite the same in any two cases of tumour-disease even of the same organ. In some cases it is not always uniform throughout the same tumour; thus preparations might be described from a cluster of infected lymph-glands under the cancerous mamma of the bitch wherein two kinds of structure in the extensive strip of primary disease are severally reproduced in different lymph-glands.

The infection of the liver is a very common sequel of cancer of the digestive tract, as well as of other cancers, and even of sarcomas (especially the melanotic) and lymphomas. Opinions differ as to the share which the liver-cells take in the building up of the new texture; but there is hardly any room for doubting that it is from the pre-existing cells of each infected area, even if it be exclusively from the cells of the supporting tissue and the capillary walls, that the elements of the secondary tumours are derived by infective transformation. The infection breaks out and proceeds pari passu at a number of areas throughout the liver-substance, affecting the whole of an area as if at one blow; there is an absolute lack of evidence in favour of the .assertion often made, that the secondary tumours are due to the mere increase, by division, of cells detached from the primary mass and lodged here and there in the liver. There is a certain amount of evidence in favour of some such embolic theory for the secondary tumours of the lungs, which are usually a sequel of sarcomatous growth in some bone or in other mesoblastic tissue. Sarcomatous tumours are apt to grow through the walls of neighbouring veins, and pieces of them doubtless get detached and carried into the pulmonary circulation; but it is more than doubtful whether even these emboli give rise to the secondary tumours of the lungs merely by continuous proliferation of their cells, and not rather by the infective action of their presence.

Another seat of secondary tumour-formation, both epithelial and melanotic sarcomatous, is the serous membranes. The accompanying figure (fig. 54), from a nodule on the diaphragm in a case of cancer of the colon in the horse, may be set beside fig. 51 as showing the substantial identity of the infective process in the secondary and primary seats of disease; in both cases the cells of the connective tissue are seen in the stages of transformation towards the epithelial form and grouping. The infection of the neighbourhood is the essence of the cancerous process. But the discontinuous infection of distant parts is not different from it in kind. It is merely “Wirkung in der Ferne,” and it is more mysterious only because it is more remote.

The disorder of secretion thus eventually assumes a cancerous character in which traces of its origin may be hard to find. As the disease persists or extends the patient’s colour becomes sallow or dull grey, the colourless cells are increased in the blood, the bones may become fragile, and general wasting (curiously associated sometimes, with local production of fat at the seat of disease) puts an end to a life of suffering. In abdominal cancers death may be hastened by dropsy of the peritoneum; in various forms of the disease there may be fatal bleeding from an eroded vessel. It has often been remarked that an appearance of exceptionally blooming health goes with the liability to cancer; and the blooming appearance of the face and plump condition of the tissues will sometimes persist when the local ravages of the disease have made considerable progress.

§ 9.— The Liabilities of Obsolescence.

We have seen in the foregoing sections that various liabilities to error underlie the embryological tissue-developments, the process of blood-making, the process of bone-making, and the process of secretion. But there are functions of the body, of its tissues and organs, in which the morbid liability is something special. The most striking instance of this is in the reproductive organs, particularly those of the female; the obsolescence of the function, and in part of the structure, in the ovaries, uterus, and breasts of women long before the natural term of life creates a peculiar liability to disease. There are two other organs, the thyroid and the suprarenal, which hold a somewhat special position; it cannot be doubted that each of these organs plays an important part in the economy, but there are suggestions in their morphology of survivalship from a former state of things, and their diseased conditions are not only peculiar in their occasion but also peculiarly important in their consequences. Lastly, there are two minute bodies situated at the bifurcation of great arterial trunks, the coccygeal gland and the intercarotid body, which are clearly marked as survivals; and the former, at least, of these carries a peculiar liability to tumour-disease during the period of intra-uterine life. These instances do not include the so-called “involution-diseases” or the liabilities of old age. The self-limitation of life may be said to be too large a problem for the present purpose; but sexual involution is a part of this problem which comes directly into pathology.

Cancer of the Breast in connexion with Obsolescence of Structure and Function.— The diseases of the climacteric period in women make an important chapter in the special pathology of the sex; together with the disorders incidental to maturation, they stand for the larger part of the special ill health of women. It will not be possible in this article to give more than a single illustration of the morbid effects of this peculiar periodicity, namely, the obsolescence of the mammary function. The statistics collected by Paget clearly show that cancer of the breast in women is peculiarly a disease of the climacteric and post-climacteric period; throughout the whole period from the age of about fifteen to about forty-five, during which the breast is capable of lactation, the cancerous disorder is rare in it, the tumour-disorders to which the organ is then liable being comparatively tractable. A few words about the physiology will serve to indicate the pathology of the simpler as well as of the more formidable malady.

The reproductive functions in the female are not only peculiar among other functions of the organism in their maturation and obsolescence, but they are further remarkable for their periodicity within the period of vigour itself. In the lower species of the vegetable and animal kingdoms seasonal periodicity is in everything, in the higher it is only in the sexual and secondary sexual characters, and in the human species it is practically confined to the reproductive system. The consequences, as regards the breast, are that its structure and function unfold during the term of gestation, continue in full vigour for a longer or shorter period (which may be arbitrarily limited), and then go through definite stages of subsidence and upfolding to the resting state. This periodical reduction of structure in an orderly way is a peculiar and unique thing; it is “as though a rose should shut and be a bud again.” The upfolding and unfolding of structure have corresponding functional aspects; there are crude secretoιy products formed and discharged, and hence it is that the breast is a peculiarly suitable organ in which to investigate the question of cellular by-products or waste of secretion, and their disposal by the lymphatic system. Compared with other secreting organs and parts the breast is not peculiarly liable to catarrh, but it has a physiological liability of its own which puts it on the same footing, as regards tumour-disease, with the great seats of catarrhal disorder, the stomach and the cervix uteri. Like these organs, it is not generally subject to cancer until after middle life; but, whereas in them the predisposition appears to depend on long-continued functional irregularities, the liability of the breast arises out of its normal obsolescence. Its secreting mechanism becomes finally-broken up, so that one may find little left besides traces of the larger ducts in the midst of wide areas of fibrillar tissue and fat. Traces of the glandular structure persist to a very various extent in different women, and even in different parts of the same breast. It is obvious that the process is one which offers numerous opportunities for a devious course; it maybe retarded, or advance unequally, or be in the end incomplete. That which in all cases must be held to create the peculiar liability to cancerous infection is the readiness of the preponderant connective tissue to be acted on by epithelial cells dispersed throughout it or otherwise in direct contact with its corpuscles.

§ 10.— Special Liabilities of the Suprarenal and Thyroid.

(1) Of the Suprarenal—Addison , s Disease.— The peculiar condition of ill health—always fatal—which Addison discovered to be associated with caseous degeneration of both suprarenal bodies was described by himself as “anaemia, general languor and debility, remarkable feebleness of the heart’s action, irritability of the stomach, and a peculiar change of colour in the skin.” Some of these symptoms appear to be due to interference with the function of the sympathetic nervous system; the disease, as a whole, however, is almost certainly the direct effect of withdrawal from the general life of the body of those services which the suprarenals are adapted to render. Where there is no caseous degeneration (and consequent non-circulation of blood) in each of the suprarenals the peculiar group of symptoms constituting Addison’s disease does not occur; there may be hyperplasia (struma suprarenalis) of one or both suprarenals, or even true cancer of one or both, but these morbid conditions do not seem to be able to produce the same effect on the organism which is produced by caseous degeneration. On the other hand, Addison’s disease has resulted in a few cases where the suprarenals had not been destroyed by caseous degeneration, but had undergone extreme atrophy. We shall best approach this somewhat intricate disease by considering it from the point of view of suprarenal function, and of the peculiar relation of the present probable function of the organ to its past morphological history.

Evidence of Suprarenal Function.— A simple experiment will show that the blood passing through the suprarenal receives important additions. If the organ taken quite warm from a recently-killed animal, such as the horse, be cut into pieces and placed in a solution of potassium bichromate the central region assumes a rich brown colour. Under the microscope the brown colour will be found to reside in the coagulated plasma filling the numerous lacunar spaces and large veins of the central region and in the cells adhering outside their walls. At the same time it will be seen that the groups of red blood-disks, wherever they occur in the coagulated plasma, form areas of bright green colour. These colour-reactions with chromium are not known to occur anywhere else in the tissues and fluids of the body; there is that in the outgoing blood of the suprarenal which reduces the orange-red chromium-salt to a brown oxide, and (in the case of the red blood-disks with more oxygen) to a green oxide. It will hardly prove an easy task to isolate the substance whose existence is thus indicated, but it is not difficult to follow in the suprarenal structure the adaptations for supplying some such substance to the blood. It is precisely analogous to the adaptation of the placenta, as described above (p. 374), for supplying its metabolic product to the blood destined for the foetus. Several arteries reach the suprarenal all round its circumference; they break up into capillaries which radiate to the centre, carrying the suprarenal cells closely adherent to their walls; towards the centi ’ e certain lacunar spaces form, and from these the central outcarrying vessel receives its blood, being provided with contractile muscular walls (in man, the horse, &c.). Whatever is added to the blood passing through the suprarenal must come from the suprarenal cells. There is reason to suppose that this addition is an actual exuded plasma, just as it is in the placenta. In the latter case the added fluid drops from the protoplasmic wall of the vessel into the circulating blood; in the suprarenal a membrane is interposed between the lumen of the vessel and the cylinders of secreting cells, namely, the wall of the vessel itself. In this respect the suprarenal cells are as well placed for contributing to the blood flowing past them as are the liver-cells for exercising their glycogenic function. We shall conclude, at least, that the suprarenal blood has received additions whilst in the organ, and that these additions have been a material exudation (plasma) from the suprarenal cells.

The caseous or nutty-like or cretaceous change which overtakes the suprarenals in Addison’s disease involves the complete suppression of this function, for it practically amounts to the arrest of circulation through the organ; blood neither enters the organ nor passes out of it, and there can be therefore no metabolism. Whatever be the nature of the services that this remarkable organ is adapted to render to the general life, Addison’s disease is the evidence that such services cannot permanently be withdrawn with impunity. The most striking effect is the formation of brown pigment, often so abundant as to appear almost black, in the lower cells of the rete mucosum in certain regions of predilection of the skin, and here and there in tlte mucous membranes. Doubtless a large part of the symptoms of Addison’s disease might be traced vaguely to disorder of the sympathetic nervous system; but, while it is difficult to prove the existence of such disorder of the solar plexus, except as an inference from the symptoms, we have the patent fact that the full train of symptoms in Addison’s disease is associated with loss of suprarenal structure and function, including naturally so much of the structure and function of the sympathetic nerve as properly belongs to the organ.

The causes of the molecular decay of the suprarenals and consequent cessation of their function are various. It may be the mere contiguity to a lumbar abscess, or. it may be a part of general tuberculous disease in the body, or it may be associated with no extrinsic morbid condition whatsoever. Enlargement seems usually to have preceded the final molecular break-down. The liability of the suprarenals (with or without preceding enlargement) to caseous degeneration must be considered to be somewhat special to the pair of organs, just as the suppression of their function is of special significance for the life of the body. The caseation soon overtakes the whole structure on both sides, so that a relatively small amount of that not very rare degeneration is of fatal import if the suprarenals be the seat of it. There is a good deal of morphological and developmental evidence that the suprarenals are in one sense obsolete, their structure being, however, adapted or utilized for new functions; associated with this adaptation of the organs we have the peculiar instability of their protoplasm, the absence of any power of recovery, and the very marked and fatal effects that follow the withholding of their contributions to the metabolism of the body.

(2) Special Liabilities of the Thyroid Gland.— The thyroid is in ' some respects parallel with the suprarenals. Its cells furnish a mucus-like plasma which is, in the first instance, poured into the ∣ closed vesicles of the organ, but is taken up again and carried into the circulation (as Baber’s observations tend to prove, Phil. Trans., 1876, 1881) by the lymphatic vessels in their walls. We have now to consider those not unimportant or infrequent morbid conditions which are associated with the peculiar functional position of this organ.

Goitre.— The grand disease in which the functional activity of ∣ the thyroid is implicated is goitre. Under certain conditions of locality a large part of the population become goitrous, that is to say, their thyroids undergo enlargement. (See Goitre.) There have also been epidemics of temporary enlargement of the thyroid in garrisons. The simple enlargement undergoes a considerable variety of subsequent changes in the different cases: it may be general or partial at the outset, it may become cystic or “aneur-ismal,” gelatinous or haemorrhagic, it may become fibrous, very generally it becomes petrified at various centres, sometimes there is a kind of osseous framework developed through its substance, and there may be amyloid concretions. These transformations are too many and complex to be entered upon, although they are full of interest for the elucidation of indwelling embryonic tendencies. The primary fact is enlargement of the thyroid among populations whose food, water, air, or environment generally has something defective or unsuitable. The enlargement of the thyroid means that the organ has greater calls upon its ordinary function, that it makes an effort to meet the circumstances of the case. And there can be no doubt that in most cases the effort is successful; for goitre, apart from the inconvenient size of the thyroid and the mechanical consequences of pressure, is a harmless condition. The subsequent changes in the enlarged organ are the inevitable consequences of hyperplasia; but the primary enlargement is conservative and adaptive. The adaptation has the effect of elaborating from the blood brought to the thyroid more of the mucous substance which it is the office of the thyroid to elaborate, the same being probably returned to the blood more or less directly. There is that in the water, food, or air of these populations, and in the nutrition of men and animals in isolated cases elsewhere, which calls for more of this peculiar metabolism.

Myxaedema.— Surgeons have in some places practised removal of the enlarged thyroid; and attention has lately been called in Switzerland to the after-effects of such removals. The connective tissue in all parts of the body has become occupied with a mucuslike substance or has shown evidence of unwonted functional and plastic activity in its ceils and fibres. Of eighteen cases of complete removal of the enlarged thyroid at the hospital of Bern this condition followed in sixteen, and in the two which escaped it an “accessory” thyroid had arisen. The condition is that which had been described by Ord as myxaedema (from the mucous dropsy of the skin), a progressive disease, with hebetude and other symptoms of impaired higher functions, and tending to a fatal result in a few years. The interesting fact is that in such cases of idiopathic myxaedema the thyroid has very generally been observed to be small or wanting; where the diminished organ has been examined after death it has been found practically reduced to a mass of connective tissue infiltrated with mucus, like the connective tissue elsewhere. The relation then between the cases of myxaedema following operative removal of a goitre and the idiopathic cases would seem to be that, in the one, a mucous condition of the whole connective tissue of the body follows when the thyroid, enlarged to meet the metabolic needs of the body, has been removed by the surgeon, while, in the other, the same condition has followed where the thyroid has either proved too small for the ordinary metabolic ends that it is adapted to serve, or has degenerated under an unusual call upon its metabolism. Of the nature of this metabolism we are ignorant; we know only that a material fluid is elaborated, and that the fluid is of the mucous kind.

Cretinism.— If reference be made to fig. 40, showing the more spongy tissue of the placenta, it will be seen that there also a fluid is elaborated and added to the blood from the richly protoplasmic Avails of the vessels; and that fluid is also of the mucous kind. It is the “uterine milk” of earlier authors, and it would appear to exude through the densely nucleated marginal tracts of the placenta where the faetal vessels and their plasmatic supporting tissue touch it. It is this great metabolic function, so essential to the vigorous development of the child, that is probably at fault in the poor and over-worked or otherwise over-taxed mothers whose offspring become rickety; and the fault may be said more particularly to be deficient quantity or quality of the placental mucous secretion. The similarity of the thyroid and placental metabolisms cannot but come into account in considering the very peculiar condition of cretinism, proper to the offspring of goitrous mothers, or of mothers who had resided during their pregnancy in a goitrous district.

Under the same endemic circumstances which cause the compensatory enlargement of the thyroid in the parents we meet with cretinism in the offspring. Although the defects of development and growth in cretinism are on the whole different from and much more universal than those of rickets, yet there is a certain parallelism between the two conditions. The cretin, like the child who becomes rickety, must have been born with the disposition. The condition is not inherited, but it is congenital,—that is to say, it is derived from the mother in respect of her pregnancy only, and that means that it is derived most of all from the placenta. Cretinism is to goitrous districts what rickets is to other localities. And, although there is no positive evidence as to the placental function either in the one case or in the other, yet the placenta is clearly pointed to in both cases; and we may conjecture that cretins are the offspring of those mothers whose maternal nutriment is impaired, not by the general hardships of those who bear rickety children, but by the special endemic conditions which serve also to tax that other mucus-producing organ, the thyroid gland. The endemic conditions may not have caused goitre in the mother, although, as a matter of fact, they generally do; but, under a special concurrence of circumstances, as common in goitrous districts as are the determining causes of rickets elsewhere, they have caused a cretinous habit of body in the child, and to do so they must have affected the placental efficiency in some manner as yet unknown.

This mode of associating goitre and cretinism assumes an error in the placental function which has not been shown by direct observation of the placenta to have existed. It has probably not been looked for; and, even if it had been, there would have been some difficulty in making out its morphological characters. Under the circumstances of the case the evidence can hardly be other than deductive.

Graves's Disease, or Exophthalmic Goitre.— In certain cases of anaemia in women there is enlargement of the thyroid, fluctuating in amount or permanent, but not liable to the common developments or degenerations of endemic goitre. Associated with the anaemia and the enlarged thyroid there are disturbance of the functions of the sympathetic nervous system and a remarkable prominence of the eyeballs. It is probable that another aspect of the thyroid function than the mucus-making is involved here. It is an old contention of Kohlrausch that the droplets of hyaline substance, often with a yellowish or pale reddish tint, that are found in the thyroid mixed with the ordinary mucus of its alveoli were an embryonic form of blood-globules. In the thyroid of the dog these droplets may be often seen of a more uniform size, and so like blood-corpuscles (allowing for irregularities of form and size) that they have been actually regarded as such, and put down, when in considerable quantities, to “haemorrhage” from the vessels that run on the other side of the epithelial wall of cells. There is not the slightest reason to suppose that these droplets have escaped from the blood-vessels; they are produced from the epithelium of the organ along with the other mucus-like fluid. They point, indeed, to a haematoblastic function of the cells, somehow correlated to their ordinary mucus-yielding function. There are analogies among the connective tissues, at least, for this correlation between mucous and haematoblastic production, in new growths, and there is an analogy in the early stage of embryonic fat-formation, in the production of red blood-disks from the same mesoblastic cells at one stage of their existence and of mucus-like fluid within them at the next. Now, although there is no evidence that the enlargement and increased functional activity of the thyroid in these peculiar cases of anaemia has a more special relation to the haematoblastic side of the function than to the mucous, yet the coexistence of an enlarged thyroid with certain cases of anaemia becomes intelligible in the light of these indications of haematoblastic function. The enlargement of the thyroid may be considered a special effort, comparable to the effort of the bone-marrow in pernicious anaemia. The profound disturbance of the vascular system which goes with this condition must stand as an empirical fact, but it may be classed with the analogous sympathetic disturbances in Addison’s disease; both the suprarenal and the thyroid are to be considered as organs in which disorder of function has a special relation to the sympathetic,—the abdominal sympathetic in the one case and the cervical in the other. It is to be observed that in common goitre, where there is not so much an alteration, diversion, or disorder of function as a compensating increase of the ordinary function, there are no symptoms referable to the sympathetic; so that the relation in the enlarged thyroid of anaemia cannot be a mere mechanical one.

Secondary Tumours of the Thyroid.— The last special liability of the thyroid to be mentioned is a very peculiar one; there is a number of well-authenticated cases in which a simple enlargement or hyperplasia of the organ has been associated with the new formation of masses of the proper thyroid-texture, with the proper mucous secretion, in the lungs and at various points of the subcutaneous tissue. In these cases the hyperplastic thyroid exhibits the property of an infective tumour, the new growth of thyroidtissue at remote points being the secondary products of infection. Is there anything in the normal overgrowth of the thyroid to account for its infectiveness as manifested on rare occasions? One of the unsettled questions of thyroid physiology is the mode of development of the new alveoli when the organ enlarges. It is apt to be too readily assumed that the new structure is formed by continuous extension from the pre-existing, by expansion or germination; but the point has been raised by observers whether the new alveoli are not formed interstitially at numerous independent centres throughout the stroma or supporting tissue of the organ, at first as small groups of cells which come to develop a space in their midst, and to group themselves as epithelium round the periphery. This is the ordinary mode of interstitial development in cancerous infection; and, if that mode be substantiated for the physiological increase of the thyroid (and the facts in the dog’s thyroid point that way), it would enable us to understand how it is that sometimes, as if in a freak, the simple hyperplastic thyroid plays the part of an infective tumour, reproducing its own likeness at discontinuous and even distant centres.

§ 11.— Errors of Metabolism.

In the foregoing sections metabolic functions have been claimed for the placenta, for the suprarenal, and for the thyroid. Connected with these obscure and hitherto almost unregarded metabolic functions are several important morbid conditions, which are mostly of the so-called constitutional sort; with errors of the placental metabolism we connect such defective intra-uterine endowments of the foetus as gave rise to rickets and cretinism in the child (and, it may be added, to some of the manifestations of congenital syphilis); with loss of the suprarenal metabolism we connect Addison’s disease; and with a compensating or conservative increase of the thyroid metabolism we connect goitre, a condition which is harmless but for its mechanical effects. It will now be convenient to pass to those greater but hardly better understood metabolic functions with whose disorders are associated some of the severe diseases of common occurrence, taking them according to the organs, and taking the liver first.

The liver-structure is very much that of a blood-gland; its system of bile-ducts is subordinate to its blood-system, just as its biliary function, though the amount of its product be great, is in modern physiology subordinate to its glycogenic. Except in connexion with Jaundice (q.vf the biliary function does not concern us; we come at once to the not uncommon and very serious malady which may be regarded as an error of the glycogenic function, namely, diabetes.

Diabetes.— Like the errors of metabolism treated of in previous sections, diabetes is a “constitutional” or general disease. It depends essentially upon the circumstance that the blood passing to the kidney is overcharged with sugar; the kidney drains off the sugar along with an immense quantity of water, so that the prominent symptom is copious urine loaded with sugar. Diabetes can hardly be called a disease of the kidneys; these organs are but the ministers of disordered metabolism whose seat is elsewhere, and their structure is not even materially altered in the disease. In pronounced diabetes sugar is everywhere. There may be half a per cent, of it in the blood, it is in all the tissue-juices and in all secretions, and it may enter into the composition of the urine to as much as 10 per cent. The diabetic patient drinks enormously (the thirst being due, it is conjectured, to the more concentrated state of the sugary blood), and eats or desires to eat two or three times more than in health; the amount of urine voided is proportionately great, and it contains a total of urea in the twenty-four hours which corresponds approximately to the high feeding. All the while there is no proper nutrition; the body wastes, the skin becomes dry, the hair falls out, the muscles become flabby, the heart’s action is weak, and the secreting organs become reduced in bulk and enfeebled in function. Wounds tend to become gangrenous, boils and carbuncles are apt to form, and pulmonary consumption is a frequent complication. The saccharine state of the fluids is favourable to the lodgment of fungi (moulds), and these are found in the centres of disease in the lungs. The disease is an example of those paradoxes that we frequently come to in the last resort in the analysis of constitutional disturbances; in spite of the enormous supplies that the organism demands (and receives), the tissues and organs are not nourished. It is only in some cases that the disease is checked by a pure nitrogenous diet. There is some maladaptation in the economy whereby there is an enormous quantity of sugar produced which is not wanted, and a great lack of that which is wanted. Where does the divergence occur from the physiological track?

The blood ordinarily contains a trace of sugar, and traces of it may be discovered in the urine. It may be permitted to regard these traces as no more than the slight margin of non-perfect adaptation which is discoverable in many structural and functional effects. But the antecedent of this sugar, namely glycogen, exists in considerable quantity in animals the moment after death, and. is assumed to exist in them during life. Although this assumption must be granted, it is not so justifiable to admit, with some authors, that the glycogen of the body is normally changed into sugar, the latter being at once disposed of in the further course of combustion.

Glycogen is now known to exist in various tissues, more particularly in inactive muscle; but it is impossible not to conclude, on the evidence, that the liver is still the organ of its choice; and Bernard’s original position, that diabetes is a disorder of the glycogenic function of the liver, may be regarded as the reasonable one. The structure of the liver is in great part an adaptation to some suöh metabolic function, an adaptation to take somewhat from the blood and to add somewhat to the blood again. The intermediate state of this metabolism is glycogen, a starchy substance which changes to sugar under the action of a ferment out of the body, and changes to sugar sometimes in the body. Various kinds of interference cause glycogen to change to sugar within the body—puncturing the medulla oblongata at a particular spot with a fine spear-like point; the administration of curare, whose chief action is to paralyse the muscles through their nerves; the administration of nitrite of amyl, whose more obvious effect is vaso-motor paralysis of the surfacevessels, causing dilatation of them. These interferences produce a passing diabetes. It has been objected that the diabetes so produced is too transitory to be counted as analogous to the grave human malady; but it is well known that the same transitory effects are not uncommonly met with in medical practice. The true and serious diabetes is merely the established and confirmed habit of turning everything to sugar, and it cannot be doubted that Bernard’s original experimental analogies are still the best clue to the nature of the disease.

These experimental interferences point to some profound upset of the nervous control. The spot in the medulla where puncture causes temporary diabetes is otherwise known to be the vaso-motor centre; the effects of nitrite of amyl are otherwise such nerve - effects as blushing; the several effects of curare are identical with the muscular limpness of fear. The observations of clinical medicine point in the same direction; a large proportion of all the cases of diabetes where the antecedents have been ascertained with any degree of relevancy are cases of profound emotional and intellectual strain, of shocks and jars and worries to the mind, and especially to the primary instincts and affections. Along with these we have a few significant cases of tumour in, or upon, or in the neighbourhood of the medulla. These clinical facts point clearly enough to some upset of the nervous control, although there are certainly few or none of the usual concomitants of nervous disturbance. The nervepaths that are implicated are the same as the vaso-motor; but the effects themselves are not vaso-motorial. Nitrite of amyl causes artificial blushing, and it also causes diabetes; in like manner those subjective states of the mind (or mechanical states of the brain) which ordinarily také such outward directions as blushing and pallor, or the vaso-motorial direction, sometimes spend themselves otherwise, causing an upset of the glycogenic adaptation. It is certainly not a simple affair of vaso-motor paralysis, even if the path of influence be the same. Some nervous mechanism allied to the vaso - motor, or using the same path of influence, is probably concerned, the same kind of unknown nervous mechanism which would appear to be concerned in Addison’s disease (of the suprarenal) and in Graves’s disease (of the thyroid). The upset of this controlling nerve-force is followed by the production of a substance from the liver-cells which is directly added to the blood as sugar, and is removed as sugar in the urine. This substitution of sugar in the blood for some other substance is fatal to nutrition; it is so wasteful an expenditure that the physiological bankruptcy cannot be averted even when the patient receives the enormous amount of food and drink for which he craves.

For the pathology of diabetes the obvious desiderata are to know the normal sources and normal ways of disposal of the glycogen of the liver. It seems to be premature to infer that, because glycogen, as its name implies, may easily become sugar, therefore it ordinarily does become sugar as a transition - stage towards some other product. If the regular conversion of glycogen into sugar be assumed, the cause of diabetes would be referred to the inadequate disposal of the sugar (e.g., its inadequate combustion in the lungs). Cohnheim, after summing up the evidence from all sources, concludes that such inadequate disposal of sugar, properly present in the body, does occur in diabetes; and he would seek for the reason of the failure in the want of some “ferment” which, in health, brings about the further breaking up of the sugar. The question, however, is a sufficiently open one for us to contend that the initial error lies in the making of sugar at all; or, in other words, that the failure of the ferment (or of the nerve-control of metabolism) has to be assigned to an earlier stage of the metabolic process.

It is probably more than an accidental coincidence that the pancreas has often been found shrunken and indurated in diabetes, the shrinkage having followed apparently on an earlier hyperplasia. According to analogy it would mean that the error of the hepatic function had thrown more work upon the pancreas. Apart from the state of the pancreas there is nothing distinctive in the structural conditions associated with diabetes.

Acute Yellow Atrophy of the Liver.— Here we have another severe constitutional disorder, but much rarer than diabetes, in which the hepatic functions are chiefly, and perhaps primarily, concerned. It arises under a variety of circumstances, the chief of which are respectively poisoning by phosphorus, profound emotional troubles, and the state of pregnancy. The early implication of the hepatic functions is shown by the existence of a degree of common jaundice for some time before the distinctive and fatal onset. The disease may be said to consist in a complete disorganization of the whole hepatic activity,—in the arrest of its biliary secretion and of its other metabolism. The liver-cells fall into a state of molecular disintegration, and the organ shrinks bodily, sometimes to a mere fraction of its original volume. The ducts contain no bile, but a colourless plasma in place of it; the cells, where they keep their outlines, are full of albuminous granules; large quantities of leucin and tyrosin are found in the organ after death. What is there common to phosphorus-poisoning, profound emotional troubles, and the state of pregnancy which can be brought into relation with this remarkable upset of function and rapid disintegration of structure?

As regards the effects of phosphorus, they belong to a remarkable class of effects, counterfeiting idiopathic diseased states, which it is the property of certain of the chemical elements, including arsenic, antimony, and lead, to induce. The action of this element may be said to be an arrest of metabolism, falling with special stress upon the great seat of such functional activity (and on the secreting cells of the stomach and kidney as well). As regards the acute yellow atrophy of the liver which follows profound emotional troubles, we have many slighter analogous instances of nervous inhibition of visceral function due to more transitory states of emotion; the disorganization of the liver-function would be the proportionate effect of a more profound and more lasting mental trouble. As to the acute yellow atrophy of the pregnant state the circumstances are doubly complex. In all the incidents of pregnancy we must take into account the placental function, a metabolism almost as great for the time as that of the liver itself; and, if we are to find atìy link of connexion between the seemingly diverse conditions here in question, we should have to resort to the somewhat vague generality that, in a rare concurrence of circumstances, the placental function makes demands upon the maternal blood and tissues, or upon the ordinary metabolisms of the mother, which are of an upsetting kind, the incidence falling sometimes on the metabolic functions of the liver.

Albuminuria.— The waste of albumen in the course of the urinary excretion is a much more frequent and hardly less serious factor in disease than the sugar - waste; but albuminuria differs from diabetes in two important respects: firstly, the albumen which escapes is, in great part at least, the proper albumen of the blood (serum-albumin and globulin); and secondly, there goes hand in hand with the error of function a series of progressive structural changes fatal to the general efficiency of the kidney itself. Albuminuria is the functional error that corresponds on the whole closely to Bright’s disease ; but it would be a mistake to suppose that Bright’s disease can be measured by the amount of albumen lost. A consideration of these complex forms of constitutional disturbance may proceed, however, from the side of albuminous leakage, and from the point of view of the adaptations in the kidney whereby the leakage is ordinarily prevented or reduced to a minimum.

The problem, as it may be called, of the renal excretion is how to discharge from the blood and from the body absolutely the washings of the tissues, or the waste-matters of metabolism, without allowing other dissolved substances of the blood to be discharged at the same time. In adaptation hereto, the kidney is in part a secreting organ and in part a mechanical filter. Those parts or regions of its structure where its epithelium is in the form of very large and richly protoplasmic cells have a true secretory function, so that nothing passes from the blood to be cast out from the body except through the interior of a very considerable cell, and in all probability through a metabolic selective process therein. This is known to be the urea-region of the kidney; and the separation of urea from the blood may be said to be the greatest of the renal functions. But by far the largest part of the urine, namely the water of it, is strained off from the blood by another kind of kidneystructure, which is more truly a mechanism; not all the water of the urine, but the greater part of it, is filtered from the blood as it passes through the remarkable coils or glomeruli of small vessels which are placed at the farther end of the tubular system. In these the structural adaptations all point to mechanical filtration and not to selective secretion. The circulation in the vascular coils of the kidney is unique as regards the balance of driving force and resisting force; the lateral pressure in these spherical coils of small vessels is greater than in any other capillary region of the body. It is indeed great enough to cause a transudation of water; but is it so nicely balanced as not to allow an escape of albumen? There can be no question that albumen does often find its way into the urine without amounting to a serious functional error or to a clinical condition of disease; and it is equally certain that the leakage takes place at the glomeruli. Albumen is found so often in the urine when it is looked for systematically from day to day that we may admit, with Senator, that any one may be more or less albuminuric from time to time. In 119 healthy soldiers, 19, or 16 per cent., had albumen in the urine; in 200 seemingly healthy persons examined for life assurance there were 24 with albumen, or 12 per cent.; in 61 healthy children, 7, or 11 ’ 5 per cent; in 32 hospital attendants in good health, 14, or 44 per cent. Add to these experiences the difficulty of detecting small quantities of albumen in ordinarily dilute urine and the impossibility of detecting certain varieties of albumen (known to occur in the urine) except by special tests, and we may safely conclude that the filtration of water from the blood in the renal capillaries is very apt to be attended with a slight leakage of albumen also. The adaptation that water should drain off, but not albumen, is a very nicely balanced one, and therefore very easily upset. As a matter of fact it is. frequently upset; the physiological albuminuria, like the physiological glycosuria, and like the small admixture of colourless cells among the multitude of blood-disks proper, is the narrow margin of non-perfect adaptation which meets us frequently in the economy of living organisms. The nicely-adjusted balance of driving .force and resisting force in the vascular tufts is constantly exposed to disturbing influences, so that one may reckon to find a certain small average of albuminous leakage.

The great occasion of this leakage is sluggish circulation through the glomeruli, whether from over-distension of the veins beyond or from other cause. The faster the blood passes through these capillaries the greater the quantity of water drained off, and the more minimal the quantity of albumen that escapes; but when the blood travels slower there is absolutely less water filtered off in a given time, and the proportion of albumen that passes with it is increased from a minimal quantity to something considerable. Thus a con gested state of the kidney, whether the embarrassment be traced to the side of influx or of efflux, to the arterial or the venous side, is favourable to the leakage of albumen, and a large part of all the albuminuria of medical practice is of that nature. 'Γhe congested state has been often experimentally induced in animals by various devices, and the laws of albuminous leakage have thus been determined with an exactitude which is very considerable. In these experiments the embarrassment of the circulation has been induced in various ways—by clamping the renal vein so as to dam up the blood in the kidney, by clamping the renal artery, by interfering with the nervous mechanisms, either at the spot or more centrally, and by introducing toxic substances into the circulating blood. Probably all of these forms of experimental interference have their analogies in disease, although the gross mechanical impediments are a rare type. The albuminuria of the pregnant state—not certainly an invariable occurrence, but rather a liability of that condition—may be referred in great part, if not altogether, to embarrassed venous reflux, for there are analogous cases of temporary albuminuria in which the cause is not the gravid uterus, but a uterine or ovarian tumour. In pregnancy it is specially apt to occur in primiparae and in cases of twins, and in the later months. Again, the albuminuria of some forms of heart-disease, of emphysema, and of chronic bronchitis is an affair of difficult venous reflux. It is on the arterial side that we have to place the determining forces of a considerable number of albuminuric cases, and these the most insidious. In all those cases where the congestion of the kidney is “inflammatory” there are the irregularities of circulation usual in inflammation, the parenchymatous cellular changes of inflammation, and the somewhat difficult correlation between these two factors in the process.. These cases may be said to exhaust the instances of albuminuria due to heightened bloodpressure. The albuminuria of cachectic subjects is known to be dependent mostly on the impaired integrity of the glomerular vessel-walls,-≈-on an amyloid change in them which permits the transudation of albumen under the ordinary conditions of pressure. But there is still a third determining cause of albuminuria, namely, a changed state of the blood when both the pressure and the state of the vessel-walls are constants.

It has been mentioned that there are two instructive points of contrast between the drain of sugar and the drain of albumen; the sugar is not ordinarily present in the blood, and its discharge by the kidney is unattended with structural changes in that organ. The albumen of albuminuria is to a great extent the ordinary albumen of the blood (serum-albumin and globulin); but in the urine there are other albumins found which are not ordinarily present in the blood, such as the variety identical with pepton, and another variety, hemialbumose, or “propepton.” The latter is found in cases of osteomalacia, and it may be detected under other circumstances as well. Even when there are no new and specially diffusible albumins in the blood, it is probable that some alteration in the relative composition of the blood—in the proportion of its salts and the like—will make its albumen more liable to transude in the renal glomeruli.

The albuminuria of phosphorus-poisoning and of acute yellow atrophy of the liver raises another possibility,—the possibility, namely, that the albumen is produced in the course of the metabolic process in the proper secreting epithelium of the kidneytubules. Certainly the large epithelial cells of the kidney in these two conditions are filled with peculiar granules of ‘ ‘ albuminous” matter. The question has to be at least entertained, whether certain cases of albuminuria may not be due to a primary disorder of the renal metabolism, to some interference with its “ferment.”

Four factors, then, are concerned in the waste of albumen, and they may act either singly or in combination. In the order of their importance they are :—(1) disorder of the vascular pressure, whereby the nicely-adjusted filtering mechanism in the glomeruli is deranged; (2) states of the blood exceptionally favourable to the diffusion of its albumen, or even the presence in the blood of peculiar forms of albumen with high diflusibility; (3) a more permeable condition of the vessel-wall (as in amyloid disease); and (4) an error in the proper metabolism of the secreting epithelium whereby an albuminous by-product is formed from it. It now remains to consider briefly the other distinctive point in the acquired habit of albuminous waste, namely, the associated structural changes.

Structural Changes in the Kidney.— If the kidneys be examined from a case in which the symptoms, sometimes lasting for years, had been albumen in the urine (with cylindrical casts of the kidney-tubules), a more or less scanty amount of urine, and a small proportion of urea, together with dropsy and marked anaemia, they will most likely be found to be enormously enlarged, and of a pale fawn colour, compared by Watson to the cut surface of a parsnip. This is the “large white kidney” of chronic Bright’s disease, the enlargement being in the outer zone of the organ, in the region of the glomeruli and secreting tubules. ‘ ‘ The incised surface gives one the notion of some deposit whereby the original texture of the part is obscured.” How comes it that an attack of congestion at some more or less remote period, or repeated congested states of the organ, have 1ed to so remarkable a result? It does not help us, for the purpose of rational analysis, to turn to “inflammation” as a last resource; what the analysis really conducts us to is the correlation between the disordered function and the structural changes.

It is impossible not to connect the remarkable form of hyperplasia in the large white kidney (or where there is also the amyloid complication) with the albuminous character of the exudation in which the organ, and more especially its cortex, is bathed. Sugar, as we have seen, has no such effect on structure, nor has uric acid, as we shall see in speaking of the kidney in gout; the albumen has a special influence on the local centres of nutrition, ou the cells and tissues of the organ. Again, the excess of nutrition does not conduct to increase on the normal lines. There are such cases of normal increase in the kidney’s bulk, as when one kidney has to do the work of two, owing to removal or congenital absence of the other. But in the large white kidney of albuminuria the increase is of an unprofitable kind; it is a hyperplasia that not only does not add to the efficiency of the organ but even seriously impairs it. The large epithelial cells of the secreting region are clouded with albuminous deposit, and their nuclei show a fainter reaction to the colouring agents; or they fall into an unstable granular condition and into molecular detritus; or they are shed bodily into the lumen of the tubule. The flattened cells of the Bowman’s capsule are less apt to degenerate; they are more likely to multiply in situ, and to build up an unnaturally thick wall around the capsule. Further, the interstices of the tubules and the margins of the glomeruli are occupied by collections of round nuclear cells, like the collections underlying a catarrhal mucous membrane. All this activity is misdirected; it does not help the function, but overwhelms it. The urine is scanty and the proportion of urea small; and these consequences may be traced, firstly to the sluggish circulation within the organ, and secondly to the complete obliteration of some glomeruli and the cumbrous thickening of others, and to the degeneration of the secreting epithelium interfering with its proper metabolism. There is hardly any tendency to restitutio ad integrum in the large white kidney, the unprofitable overfeeding of its elements continuing to the end.

Contrasting with the large white kidney is the contracted kidney in another variety of chronic Bright’s disease. For the present purpose it is necessary to follow the broader lines of distinction, and to avoid the transitions and finer shades in the pathology; and it may be stated as a general truth that the large white kidney goes with scanty urine and much waste of albumen (the waxy modification having only the latter), while the small granular contracted kidney is associated with even copious urine and a waste of albumen which is often small, and in any case variable. The error in these latter cases appears to lie with the arterial side of the circulation; the left heart is hypertrophied, and so is the muscular coat of the arteries in the kidney, if not also elsewhere. It is essentially an interstitial disease of the kidney, leading to enormous development of its supporting tissue; whole tubules become obliterated, but in those that remain the epithelium is not degenerated. Obliteration also overtakes the glomeruli, but there must be a compensating increase in the work done by those that survive to account for the copious urine; it often happens, also, that numerous small cysts are produced.

Shrinkage of the connective tissue after a period of revived embryonic activity is the cause of all these changes; it is the ordinary shrinkage of cicatricial tissue, and it has the effect of compressing the proper urinary apparatus—the filtering and the secreting—to its destruction. The kidneys may be reduced even to onefourth of their natural size, and their uneven surface shows that there has been mechanical dragging along certain lines. In the end the urea-waste accumulates in the blood to such an extent that death results, usually from uraemic coma and convulsions. In some cases cerebral haemorrhage anticipates the fatal effect of uraemia.

The small granular contracted kidney is usually of a reddish-brown colour, but it may be whitish, in which case the lobulation of its surface is larger. It is one of the standing difficulties of renal pathology to decide whether the small contracted kidney is not often a later stage of the large white. But there can be hardly any doubt that it is oftenest the structural manifestation of an entirely different disease, an arteria! disease. That which has been emphasized by s'orne pathologists as the distinctive process in this affection is the overgrowth of cells on the inner wall of the arteries, the so-called endo-arteritis or arterio-capillary sclerosis, whereby the lumen of the vessel tends to be occluded. But it may be made a question whether this is not really a part of the revived embryonic activity in the connective tissue, whose shrinkage gives the organ its granular contracted character. The interest would thus come to centre in the error of nutrition whereby so much activity is diverted to the connective tissue, an activity that takes the embryonic formative direction. We have a close analogy in cirrhosis of the liver, a disease associated with the drinking of raw spirits; and it is noteworthy that the insidious form of Bright’s disease, whose morbid anatomy is summed up in the small contracted and puckered kidney, occurs most frequently in those who sustain themselves more by ardent spirits than by ordinary food, and next most frequently in the subjects of gout and of lead - poisoning, although there are a good many cases of the disease remaining to be accounted for by less obvious causes.

The dropsy of Bright’s disease is difficult in its pathology. The watery state of the blood, or the hydraemia, consequent on the loss of much of its albumen does not suffice by itself. A subsidiary hypothesis, adopted by Cohnheim, is that the blood-vessels of the skin become unusually permeable. Sometimes the dropsy appears first round the ankles, at other times it shows itself in puffiness of the eyelids and a somewhat bloated pallor of the face.

Gout and the Uratic Diathesis. — Many other states of the system besides podagra—the disease which usually begins in the night with pain and redness of the great-toe joint—are now reckoned as belonging to gout. The disease, in the extended use of the name, is indeed a widespread error of metabolism which may manifest itself in very various ways. The particular liabilities to error arise during the metabolism of proteids, from the first stage of digestion in the stomach to the last stage of excretion in the kidney. Hence it is that gout, in its widest meaning, has been taken to be a form of “dyspepsia.” The opportunity for going wrong may be said to depend on the fact that there are two chief forms of nitrogenous waste remaining to be got rid of in the end, which are somehow correlated to one another,—the highly soluble substance urea, and the highly insoluble substance uric acid. There are remarkable differences in the proportions of these two waste-products throughout the animal kingdom; in most reptiles and in birds the form of nitrogenous waste is mostly uric acid, whereas in man (and other mammals) it is mostly urea. But in man the waste is still to a small extent in the form of uric acid. In normal human urine the proportions are to 1500 grammes (52‘91 ounces) of water in the urine of twenty-four hours the total of solids is 72 grammes (2’54 ounces), of which 33 - 18 (1 ’ 17 ounces) are urea, and only •555 (- 019 ounce) uric acid, or not more than one-sixtieth of the quantity of urea. Whether or not we are to regard this small margin of uric acid as another of those instances of non-perfect adaptation of which we have previously found instances in the physiological traces of sugar and of albumen in the urine, and of colourless corpuscles in the blood, there can be no doubt that the adaptation, such as it is, whereby the nitrogenous waste is mostly the highly soluble urea, but to a very small amount also the less soluble uric acid, is the occasion of many and serious morbid conditions. The liability to these gouty and calculous disorders depends partly on the increase of uric acid at the expense of the urea, together with the low solubility of the former, but it seems to depend also on an abnormally low power of the animal fluids to dissolve uric acid, or of the kidney to eliminate it when its quantity is not excessive.

The peculiar liability from uric acid is sometimes called the uric-acid or uratic diathesis or constitution; some persons have it much more than others, and it is exceedingly apt to be handed down from parent to offspring, so that the stock, in countries and among classes where gout is common, may be said to be widely inoculated with it. Where the acquisition of it can be traced at first hand it is often found that the associated circumstances are high-feeding and a life of physical inaction and feeble intellectual zest. These are among the best-known conditions of gout, admitted equally by the ancients and the moderns. It is now known, however, that practically the same gouty constitution may be and often is induced by conditions which have hardly anything in common with luxury. Thus gout is a common liability of workers in lead, being one of the various manifestations of lead-poisoning; it is also common among those classes of labourers, such as docklabourers on the Thames, whose habitual drink is porter; and it is said to have become common among the working-class in Dublin, where it was rare twenty or thirty years ago, according as they have taken to drinking porter instead of ardent spirits. There are still other cases of gouty constitution for which neither heredity, nor luxury, nor lead-poisoning, nor porter-drinking can be invoked as an explanation; and these are the cases which justify the somewhat wide definition of gout as a form of dyspepsia.

In order to have the gouty effect there need be no great increase in the amount of uric acid formed in the course of the metabolism of proteids. During an acute attack of gout, and previous to it, the amount of uric acid in the urine will probably be much below the average; it is the kidney that has failed in its function, so that the uric acid is retained in the blood to be depositçd elsewhere. The presence of uric acid (urate of soda) in the blood in gout is the well-known discovery of Garrod, who has also pointed out that its proportion in the urine is at the same time reduced. But there need not even be failure of the kidney’s function, although, as a matter of fact, there often is; the error may lie in the heightened insolubility of the uric acid. It is observed that the uric acid of urine is apt to be deposited in the form of urates, as a brick-red sediment, even when there is no excess of it; a more acid state of the urine seems to favour the precipitation of the uric acid: and it has been conjectured (from the success of the alkaline treatment) that there may be some analogous acidity introduced into the blood and lymph in the form of organic acids (produced in the course of faulty digestion), which would cause the uric acid to be deposited from the blood as it circulates generally. It is in the cartilages of the joints that the deposition usually takes place, the great-toe joint (metatarso-phalangeal) having a quite remarkable and inexplicable liability. The surface of the cartilage is crusted with patches of a whitish opaque substance, which proves to be needle-shaped crystals of urate of soda; the deposition extends deeper and affects the fibrous structures of the joint; it may be so extensive in other fibrous structures as to amount to tophi or chalk-stones. In some rare cases of gout such organs as the parotid glands may be completely disorganized by the chalky deposit, or there may be numerous centres of its deposition in the membranes of the spinal cord.

Albuminuria and Eczema of Gout.— Two morbid conditions are so frequently associated with gout as to be part of its natural history, namely, eczema of some regions of the skin (eyelids, back of neck, &c.) and albuminuria. We have absolutely no clue to the connexion between the skin-disease and the uratic diathesis; for the albuminuria a connexion may be suggested. The albumen will at first be absent in the intervals of gouty attacks, showing itself during the attack, or for a few days previously; its appearance in the urine thus coincides, so far as it goes, with the decrease of uric acid in the urine. It is impossible to exclude the possibility that the albumen is here an error of the renal metabolism. All the facts of the gouty constitution point to a far-reaching disturbance of the metabolic functions, which may be induced by causes so different as lead-poisoning and a luxurious life; uric acid is not the only metabolic product concerned, although it is the chief, for there is even an occasional implication of the glycogenic metabolism, as shown by the presence of sugar in the urine, and there is the much more common albuminuria. It is impossible to believe that there are structural changes in the kidney to account for the earliest occurrences of albumen in the urine in gout, for the urinary secretion may be normal for long intervals; and it is by no means certain that the albumen is a leakage from the glomeruli owing to the altered pressure of congestion.

The kidney in chronic gout may be affected in obvious characters; it will show, on section, streaks of white opaque substance within or between the tubules,—that which is between them being composed of crystals of urate soda often in fan-shaped bundles, while that which is within them is an amorphous mixture of urates of ammonia and soda and uric acid. The so-called gouty kidney may and often does assume the progressive structural changes which lead to the state of contraction and puckering. (There are other renal deposits of uric acid, as in new-born children, which are transitory. )

The uric-acid diathesis may manifest itself, not in gout, but in gravel. In this case the excess of uric acid is thrown into the tubules of the kidney, where it forms concretions; these may either be washed out by the urine as fine grains, or may remain for a time to increase by accretion, forming renal and vesical calculus.

Obesity, Local Formations of Fat.— The significance of fat under all circumstances in the animal body is by no means well understood, but it may be conveniently approached from the side of metabolism. Adipose tissue is a somewhat special development of mesoblastic tissue, and most usually of the common binding tissue. The embryonic cell transforms the greater part of its protoplasm into an oily fluid which contains no nitrogen, the nucleus being retained on one side along with a narrow fringe of cell-substance; a fat-cell in its early stage thus resembles a signet-ring, and in its later development it becomes a thin-walled vesicle which may be distended by its oily contents much beyond the limits of even the largest cells of other tissues.· This transformation may happen to the cells of the connective tissue in almost any part of the body; but in the ordinary course of development it has certain seats of election, such as the stratum of gelatinous tissue underlying the kidney and the subcutaneous tissue. All synovial and serous membranes, except those of the liver and lungs, are favourite seats of fat-formation. In the subcutaneous tissue the first formation of fat appears to be associated with local formation of blood, the same mesoblastic elements being at one stage haematoblasts and afterwards, in their vesiculated state, fat-cells. It cannot be doubted that there is a close adaptation to the needs of the economy in the vicissitudes of the fat-tissue; but it must be admitted at the same time that the adaptation is often singularly obscure. In many cases the changes in the fat-tissue seem rather to be a correlated necessity.

One of the earliest facts that we meet with in this connexion is the gradual replacement of the thymus gland by fat, the fluid being absorbed in its turn, and the mass of tissue shrinking. Another fact of the same kind is the change into fat-cells of “lymphoid” cells elsewhere, as the change of red marrow into yellow marrow in the central canals of the long bones. Both of these changes have a prototype or an analogy in the transition that one sees in groups of the subcutaneous spindle-shaped cells from a haematoblastic activity to a fat-making activity. The season of puberty is a time of active fat-formation, more especially in women, and notably in the breast-region. A still more remarkable development of fat occurs in many eases of sterility, and in many women after the child-bearing period has ceased in ordinary. Such instances of a greater or less degree of obesity are so clearly associated with the obsolescence of an important function that they may be called physiological. Other instances of obesity have no such obvious or uniform association. Thus, an obese habit may follow one or more attacks of malarial fever; it sometimes occurs as one of the lifelong changes induced by an attack of typhoid fever. There is often a great degree of plumpness along with the extreme ill health of chlorosis. Idiocy and some forms of insanity are apt to be associated with fatness; in the pseudo-hypertrophic muscular paralysis of boys the connective-tissue cells between the muscular bundles become so active in fat-making that they usurp the place of the muscle. As an effect of dietetic errors obesity usually follows the inordinate consumption of starchy and saccharine substances, and especially the drinking of much beer, stout, and even other forms of alcohol. As a racial character obesity is found among the negro populations in some parts of Africa (South Africa and the Upper Nile).

Among the most extraordinary developments of true fat are those cases where it develops locally in association with cancers or other malignant tumours. Thus, in a boy who had suffered amputation of the leg for a malignant tumour of the tibia there was a recurrence of the disease in the stump and in the ilium; he died in a state of extreme emaciation of all the body except the thigh of the affected side, which was enveloped in a layer of ordinary subcutaneous fat half an inch thick all round, contrasting strangely with the wasted limb of the other side. To take another unambiguous case, an extensive development of fat through all its embryonic phases can actually be traced in the serous covering of the rectum in a case of cancerous stricture of the part. There is usually much local development of fat round the sac of an old hernia. In certain glandular organs, such as the pancreas, the supporting connective tissue sometimes takes on an extensive fat-forming activity, so that the organ is half transformed into adipose tissue; the same may be found around the pelvis of the kidney in old age.

Lipomatous Tumours.— It is not always possible to say whether a local development of fat should be called a lipoma or not; thus, the fat around an old hernia may be so circumscribed as practically to amount to a fatty tumour, and that may be the case also with the fat around the breast or behind the eyeball. On the intestine, notably the transverse colon, the masses of fat do become pendulous fatty tumours (much more often in the domestic quadrupeds than in man) of a uniform or lobulated structure, which may hang by a long and slender vascular stem, like an apple or a cherry on its stalk; when the vascular supply is kept up with difficulty these pendulous masses of fat tend to become calcified or otherwise sclerosed, and to fall off into the abdominal cavity as “loose bodies.” The loose bodies of the joints originate sometimes in the same manner from the pendulous masses of subsynovial fat. On the peritoneal surface the pendulous growth of fat may have a short stem and abundant blood-vessels, and go on to form a large lobulated tumour; but more usually in that situation the tumour-habit is established at a number of points, leading to the condition of multiple lipomata. The lipomata of the subcutaneous tissue may be single or multiple; if they are not congenital they are most often associated with a general obese habit; and they may grow to an enormous size. The submucous tissue of the stomach or intestine is a comparatively rare seat of fatty tumour. The most inexplicable lipomata are those which form, under very rare circumstances, as circumscribed nodular masses in the interstitial connective tissue of the cortex of the kidney, and in the subarachnoid tissue of the brain and spinal cord.

It is convenient to place these occurrences of obesity, of local overgrowths of fat, and of lipomatous tumours under the head of errors of metabolism, but it is difficult to find one physiological rationale for them all. Where obesity is due to dietetic errors we may say that the carbohydrates supplied to the body have been more than the combustion could overtake, and that the residue is “stored up” as fat. Where there is a degree of embonpoint in such a malady as chlorosis we may say that the feeble oxygen-carrying capacity of the red-blood corpuscles has led to an inadequate combustion of the carbohydrates supplied in due quantity, and that the residue has been stored up in that case also. In the unhealthy fattening that sometimes follows malarial or typhoid fever it does not appear why there should be the residue requiring to be stored up. Again, there are persons of an obese habit (probably congenital) who avoid a diet of carbohydrates, but turn even their meat diet to fat, just as there are confirmed diabetics who turn everything to sugar. Still further, we have the very remarkable tendency to make fat when the reproductive functions have ceased either prematurely or in the ordinary course; and that is a frequently occurring case which can hardly be brought into the doctrine of inadequate combustion of carbohydrates. The peculiar liability of the connective tissue between or upon the bundles of muscle to become fat-tissue may point to some defective combustion in the work done by muscles. In the cases of pseudo-hypertrophic paralysis of the leg-muscles in children we are confronted with an enormous development of the same process. Other cases of local fat - formation, as in the interstitial tissue of the pancreas or around the kidney, are still more inexplicable. Lipomatous tumours, where they are congenital, may be referred to an early error of tissue-growth; where they are acquired, we have usually a coexisting or previous obesity (local or general) to resort to, and the only difficulty is to understand how the lobules of fat came to acquire the delimitation or individuality of a tumour.

- Degenerations.— In a nosological outline there is perhaps no more convenient place for some remarks on the general subject of degenerative changes than at the end of sections dealing with the liabilities of obsolescence, the special liabilities of the suprarenal and thyroid, and the larger errors of metabolism.

The usual healthy appearance of the most elementary kind of protoplasm is a soft translucent grey; under the microscope this greyish protoplasm is uniformly and finely granular. From that standard of health there are various deviations, representing various kinds or degrees of degeneration. The chief degenerations are the mucous, the albuminous, the fatty, the calcareous, the caseous, and the amyloid.

The mucous change proceeds on more obvious physiological lines than most of the others; it is, as we have seen, the proper destiny of surface-epithelium in many situations; and we have found also, in treating of myxomatous tumours, that even in these it has not very remote affinities to the haematoblastic function. A somewhat obscure form of it, the colloid change, has been mentioned in connexion with cancer of the stomach and breast

The albuminous change is that which is often found in the large glandular cells of the liver, kidney, &c., in disorders accompanied by a rise of temperature. The cells are somewhat swollen, and their substance is clouded so as to obscure the central nucleus.

Merging imperceptibly with the albuminous degeneration is the fatty, in which numerous small droplets appear in the cell-substance, which is no longer uniform but diversified with highly-refracting granules; these droplets are of the nature of fat. In the liver-cells the droplets may run together, so that the liver-cell has the ordinary appearance of a physiological fat-cell. But there is in general a broad line of distinction between the transformation of protoplasmic substance into fat (usually in the connective-tissue cells) and fatty degeneration as above described. The latter occurs under many circumstances. It is an accompaniment of phosphorus-poisoning and of those idiopathic states which run parallel with the former, such as acute yellow atrophy of the liver. It is apt to occur in the inner coat of arteries in chlorotic subjects, producing yellowish opaque patches, which sometimes give rise to erosions. The arteries of the brain are liable to a similar degeneration more universally and under other circumstances than chlorosis. The very common condition of atheroma of the large arteries (especially aorta) is a more extensive degeneration of a fatty kind, on the basis of antecedent swelling or increase of tissue in the deeper part of the inner coat, or in the interval between the inner and the middle coats. This variety of fatty change is often associated with the production of cholesterin scales, and with a subsequent calcareous transformation. Although it is most common after middle life, it is not a senile change proper, inasmuch as the most long-lived persons have none of it.

The calcareous degeneration is most often found in the cartilages of the ribs after middle life; but, like the atheromatous change, it is not properly senile, as the very aged sometimes have their costal cartilages quite soft. The deposition of lime-salts (carbonate of lime) is in the capsules of the cartilage-cells; on applying a drop of hydrochloric acid to a thin slice of such cartilage an effervescence of carbonic-acid gas will occur. Lime is often deposited in the enlarged thyroid of goitre, and it is sometimes found in degenerated areas of the placenta. In the suprarenal it is much rarer than the cheesy degeneration. Fatty tumours in the lower animals, especially in the bovines, are liable to become calcareous; and the presence of granules of lime is a very common feature (along with the cheesy degeneration to be next mentioned) of the peculiar form of tuberculous .growths of the serous membranes, or tuberculous nodules and infiltrations of the viscera and lymphatic glands, in those animals. In other tumours, of man or of animals, it is much less common. Lastly, foreign bodies lodged in the tissues, and the encysted trichina-parasite in the muscles, acquire a deposit of lime in the thickening of tissue which forms their capsule.

The caseous or cheesy form of degeneration is the characteristic disintegration that the cells and tissues undergo in tuberculous and scrofulous disease. Collections of pus, as in chronic abscess of the liver or in chronic empyema (pus in the pleural cavity), are liable to the same process of drying up and molecular disintegration. In the central parts of hard cancers also it is not unusual to find cheesy areas. A form’ of degeneration not very unlike the caseous may be observed as a perfectly normal incident in the deeper parts of the placenta. It is by far the most common degeneration of the suprarenal cells, whether in association with general tuberculous disease or not. Under all these circumstances the caseous change follows upon a certain amount of hyperplasia of the tissue, for the maintenance of which there has been no adequate provision in the way of new blood-vessels.

The gummatous degeneration of the products of syphilitic infection is not always easily distinguished from the caseous; but, for the most part, the substance is firmer and more cohesive, as the name implies, less dry and friable in the section, and of a brown colour rather than of the yellowish or fawn colour of cheesy degeneration.

A vitreous, hyaline, or waxy degeneration of muscular fibre occurs in the courseof some fevers, as well as in progressive muscular atrophy.

The amyloid degeneration is the most peculiar of them all. The degenerate substance was thought to be allied to starch (whence the name) on account of the reaction with iodine (mahogany-red), but it is now known to be a nitrogenous principle. When it is present in large quantity, as in the amyloid liver, it gives the cut surface a peculiar glance, like that of fat bacon, and hence it has been called lardaceous or waxy degeneration. Its proper seat is the walls of the smaller arteries and the capillaries; these undergo a kind of hyaline swelling, like the swelling of boiled sago, so that the aggregate effect in such an organ as the liver is to make it very much larger, firmer, and more rigid in its outlines. This alteration in the vessel-wall facilitates the escape of the fluid part of the blood; hence the amyloid change in the kidney is a cause of albuminuria and in the intestine of diarrhoea. In the wall of the intestine the course of the amyloid vessel may be tracked by the mahogany - red line left by iodine. This remarkable form of degeneration of the vessels is associated with long-standing suppuration (especially in diseases of bone), with chronic dysentery, syphilis, and other of the constitutional states called cachectic.

§ 12.— Errors of the Nervous Control.

Reference has already been made to the obscure implication of nerve-control in such disorders as Addison’s disease, Graves’s disease, diabetes, and acute yellow atrophy of the liver; the integrity of the controlling nerve-force may be said to be necessary to the perfect carrying out of the give-and-take of metabolism, or to the full effect of the “ferment” in each of the breaking-up processes. In a subsequent section (p. 393 sqf) reference is made to another controlling nervous mechanism, whose paralysis or disorder is immediately accountable for a very large part of the sum-total of sickness in the world, namely, the mechanism which regulates the animal heat. The present section will be devoted to a few morbid conditions of the cerebro-spinal system, selected to illustrate pathological principles.

Neuralgia and Tetanus.— One or two instances of neuralgia and of tetanus will serve to illustrate a peculiarity of the disorders of the nervous system among morbid processes of the body. A person in getting up from a stooping posture before the fire hits the right eyebrow hard against the edge of the mantelpiece; the blow has touched the filaments of the supra-orbital nerve, and there is more or less of pain for a time over the limited area to which these small sensory twigs are distributed. Several weeks afterwards, when the accident had been forgotten, there is an attack of severe neuralgia over the whole of that side of the face; the pain shoots along all the nerve - branches above the eyebrow, along all the branches below the eye-socket (infra-orbital), and along the branches going to the skin of the lower-jaw region or chin. The sequence of events means that the injury to the branch of the trigeminus above the eyebrow has touched the trunk of the nerve in such a manner that, after a considerable interval, intermittent attacks of pain are felt along all three sets of branches covering the whole of one side of the face. In other words, a molecular condition of nerve, originally peripheral and limited, has become central and diffusive. Another instance is as follows. A person seated at a high desk day after day exposes the outer side of the ankle and region of the Achilles-tendon to currents of cold air from the opening and shutting of a door, some occasional pains being felt where the external saphaenous nerve runs behind the outer ankle and over the outside of the heel. After a lapse of time there is an attack of sciatica, the first of a series continuing for years, in which the course of the diffusive pain can be tracked, as if it had had an anatomical knowledge of the nerves of the limb, along all the branches of the great sciatic nerve to the thigh, leg, and foot. In this case the sequence of events is the same as in the former: the original excitant had touched the terminal twigs of the external saphaenous branch of the great sciatic nerve; after an interval intense neuralgic pain begins to be felt far up the great nerve-trunk itself; and the pain diffuses itself not only to the filaments belonging to the external saphaenous branch but along all the branches. A limited peripheral disturbance has, after an interval, become central and diffusive, and the pain apt to recur intermittently for years after.

Let us now take a case of tetanus involving the very same peripheral nerve as the last case. A boy engaged on a farm chafes the outer side of one heel by wearing boots too large for his feet; the abrasion, which is exactly over the course of the external saphaenous nerve, is disregarded, and the irritation of the boot permitted to continue. In a few days he is admitted into hospital with tetanus, that is to say, with the neck-muscles rigid, the jaw locked, the features drawn, the recumbent body bent forwards from time to time like a bow, its whole weight resting on the head and heels, occasional wild jerkings of the limbs, and the muscles everywhere as hard as boards. This horrible and painful state of the muscular system usually ends in the patient dying after a week or ten days or less, exhausted by hunger and thirst and want of sleep, or by inability to breathe under the vice-like grip in which the chest is held by the muscles of respiration. The sequence of events is here closely parallel with that in the cases of neuralgia: an irritated condition of a small outlying nerve-twig, which is not a motor nerve, has, after a short interval, touched the spinal cord in such a manner that motor force is freely and continuously let loose over the whole muscular system, with occasional discharges of a more intense kind. Spasm commencing in the muscles near the injury has been spoken to by the patients or attendants sometimes; but the observation has been recorded, on the whole, seldom. Strangely enough, it is in the muscles of the face, neck, and throat that the tetanic rigidity shows itself first, in whatever part of the body the injured nerve may be. There probably always is an injured nerve somewhere, although it is necessary to admit a few cases of “idiopathic” tetanus in which the nerve-injury is unknown. Gunshotwounds of nerves are most likely to be followed by tetanus, as well as lacerated, contused, and punctured wounds generally, including the bites inflicted by canine teeth. The tetanic onset may follow the wound immediately, or it may come on while the wound is “cleaning” or suppurating, or during the stage of scarring, or some time after the cicatrix has formed. A wound which has been neglected in' the healing, in which foreign particles have been left, or in which the nerve has been involved in the tightening of the scar is most apt to be followed by tetanus. A certain temperament, or state of the mind and body, predisposes to it; the frequency of tetanus in war may be due to more than one cause, but it seems necessary to include among the predisposing factors the excitement or preoccupation of the battlefield. Certain states of climate predispose to it; in the dry Australian air it is not uncommon for wounds to be followed by tetanus, and the disease is equally common within the tropics, especially under the circumstances which ordinarily cause chill. Among animals the horse is particularly liable to it, especially as a sequel of castration. The rise of temperature in tetanus is probably the effect of the excessive muscular metabolism.

Explosive Discharges of Nerve-force on slight Provocation.— Instances of neuralgia and of tetanus as the sequel of a peripheral injury, or series of scarcely öbserved excitations, are illustrations of that remarkable property of the nervous system which Rindfleisch speaks of as involving a “disproportion between cause and effect.” The central nervous system, he says, “has a capacity for absorbing enormous quantities of centripetal or ingoing excitations as if they left no trace; but in reality it stores them up in the form of potential energy. It is this that enables an impression which may hardly exceed the limits of physiological excitation, but is aided in various ways by circumstances, such as inherited feebleness, lowered nutrition, or blood-poisoning, suddenly to let loose the whole store of these accumulated forces and to give rise to an outbreak of the most acute feelings and the most powerful movements.” The want of outlet at the time is an error that underlies much of nervous disease, both purely psychical and other. The brooding upon wrongs, real or imagined, the unsatisfied hunger for sympathy, pent-up or unexpressed emotion under many circumstances, even the solitude of shepherds on the Australian and New Zealand downs, are among the causes tending to a total unhinging of the mind. Such illustrations of the general principle are beyond the scope of this article; the illustrations that concern us most at present are found rather in the province of reflex nervous activity, where the response is automatic, not always recorded by the consciousness, and little if at all controlled by the will. Some disorders in this group are purely functional, that is to say, there are no concurrent structural changes. In others, the functional disorder is attended or closely followed by degeneration; and these are mostly diseases of the spinal cord. Representative instances from each of these two classes will now be adverted to briefly.

Convulsions (Eclampsia).— Apart from the convulsions of uraemic poisoning, there are two prominent divisions of eclampsia—the convulsions of infancy and childhood and the convulsions of the pregnant or puerperal state. In infancy the reflex movements and uncontrolled spontaneities are predominant, just as the impressions from the outer world are but little discriminated or retained. It takes little to throw some infants into a fit; the irritation of teething, of ill-digested food, of worms, and the like will suffice. Whether in these cases, the excitations have been accumulating or not, the discharge of outgoing energy is always explosive. The muscles that straighten the back are contracted to the utmost, and the air is forcibly expelled from the chest with a prolonged cry; the head is thrown back, and the arms and legs kept rigid. The state of rigid spasm (tonic contraction) is succeeded by rapid contractions and relaxations (clonic) of the muscles of the face and limbs and whole body, which gradually become more comprehensive in sweep and slower in rhythm until they cease. Consciousness has meanwhile been suspended, and does not return until some ten or twenty minutes after the convulsive movements have ceased; with the return of consciousness the patient “comes out of the fit.” The liability to such attacks diminishes very strikingly as the intelligence and the will develop and the body hardens. It is not until the circumstances of pregnancy and childbed arise that any liability to convulsions at all comparable to that of infancy is again met with. No analysis of the circumstances of puerperal convulsions can be attempted here; if they are in some cases of “uraemic” origin, in association with the albuminuria of pregnancy, there are other cases that are primarily disorders of reflex innervation.

Epilepsy.— An epileptic fit does not differ materially in its phenomena from a fit of convulsions as above described; the tongue is more apt to be caught between the teeth in the rapid movements of the lower-jaw muscles, and the spectacle of a grown person in a fit is more distressing in every way. That which really distinguishes epilepsy from eclampsia is that it is a habit of the nervous system, with a good deal of regularity in its recurrences. Fits of convulsions in infancy will cease when the cause is removed, when teething is over, or worms expelled, or after the probationary state of the nervous system has been outgrown. The convulsions of childbed also, if the patient happily survive the attack, come to an end when the critical state of the system has passed. But it is the distinctive mark of epilepsy that it tends to become an ingrained habit, that the fit is there in posse, as if detached from its exciting cause, established, permanent, and self-existent on the paths of ingoing and outgoing nerve-influence. This tendency of a disordered reflex action to repeat itself is the same “memory” that has been claimed by Hering for the cells and mechanisms of the body generally. That which is implied in the original use of the word, namely, retentiveness or the resurrection of past impressions, and the contagion of associated ideas, is a mystery large enough to cover the minor mystery of morbid habit. Epilepsy is, as it were, the self-existent memory of a disordered reflex; and this is what we may understand by the term “neurosis.” It is true that a primary disorder of reflex action due to an adequate cause, such as infantile or puerperal convulsions are, cannot be always shown to have occurred at one time or another in epileptics. In a certain proportion of cases there has been an injury to the skull, or there are evidences of tumour or other new formation within the skull, or there is a tumour of a peripheral nerve, or a nerve involved in the scar of a wound or sore; but there are many more epileptics in whom such antecedents cannot be made out. The habit, in fact, is one which tends to be ingrained not only in the individual who has begun it but also in his or her family. Epilepsy is one of the clearest instances of a liability transmissible from parent to offspring. The heredity of epilepsy has even been proved by Brown-Séquard for the guinea-pig; when an epileptic habit was induced in guinea-pigs by injuring the spinal cord or the medulla oblongata, or by cutting the sciatic nerves, the litters of such epileptic guinea-pigs were apt to have epileptic seizures, attributable to nothing but inherited liability. According to Hasse’s figures, epilepsy has begun before the age of twenty in by far the larger number of cases, and that fact is doubtless an index of the extent of hereditary influence. If we do not assign all such cases to heredity, the advent of puberty in girls may be held to be itself a cause of epilepsy; that time of life is distinguished by the somewhat abrupt acquisition of a much wider emotional and intellectual range, and presumably by some special liability to explosions of reflex nerveforce upon slight provocation.

Chorea (St Vitus’s Dance).— This is another variety of uncontrolled movement which is also a habit, like epilepsy, and is practically confined to girlhood and boyhood. It may occur in pregnant women, but it disappears with delivery. The movements are intermittent, beginning from a state of repose with a certain fidgety restlessness, and going on to the most irrelevant and unrhythmical jerkings, hitcnings, and twistings of the limbs, head, and body, or of one limb only, or one shoulder, or of the head only, or of the tongue. The muscles do not cease to be the ministers of the will, but voluntary movements are performed with some want of aim and certainty; and the gait in walking may be seriously affected. The choreic movements themselves cannot be restrained by the will; excitement and self-consciousness intensify them; and they cease during sleep. One of the most singular facts in this strange nervous habit is its association with rheumatic fever; a significant proportion of those subject to it are found to have had rheumatic fever, but there are others, curiously enough, who afford indications only of that state of the endocardium (or lining membrane of the heart and its valves) which often goes with rheumatic fever. This fact of endocarditis has suggested a theory that the disease is due to the minute arteries of the corpus striatum being blocked with small fibrinous plugs washed off from the inflamed interior of the left ventricle, or from the surface of its valves. It is more accordant, however, with all the phenomena to regard the disease as a functional habit of muscle and nerve, with the usual intermissions of a nervous habit and the usual exacerbations, in which the implication of the heart-muscle creates a peculiar liability to endocarditis. A further analysis is offered at the end of the remarks on rheumatic fever (p. 398).

Mimetic and Epidemic Chorea. — The choreic habit has, like hysteria, a singular power of becoming a fixed idea in others; there is no doubt that choreic movements are involuntarily mimicked by young persons who witness them in orphanages or other institutions where a number of girls are living under the same circumstances of work and leisure. Chorea may thus be said to be contagious, while epilepsy is hereditary. It is no great step from these cases, which depend solely upon the fantastic trick being caught under the influence of the idée fixe, to the remarkable epidemics of dancing frenzy of λvhich some are historical, and of which there are still instances occurring from time to time under some general excitement, particularly the vivid prepossession of a large number of persons at once by the same religious hopes and fears.

In this connexion come certain other diseases— ecstasy, catalepsy, and hysteria— of which the details are given in the respective articles, Ecstasy, &c.

- Diseases of the Spinal Cord.— In the foregoing group of errors of the nervous control we have had to consider a mere functional condition,—a molecular state, no doubt, but one which cannot be seen any more than can the electricity in a wire. Structural changes, when théy occur at all, are a very late effect, as in some cases of epilepsy. But there is a very large and important part of the functional errors in the controlling nervous mechanisms which are associated with textural changes or degenerations. The most obvious of these are disorders of the reflex functions of the spinal cord. In respect of these structural changes accompanying functional irregularities, the spinal cord approximates to the organs and parts of the body which we have already considered. But there is one character in the textural changes of the spinal cord (and of the brain) which is in a sense unique, namely, their tendency to spread up and down in the particular tracts of fibres. Hence the ascending and descending degeneration and sclerosis of the cord, the extensions of bulbar paralysis, and the like.

Locomotor Ataxia, or Tabes Dorsalis.— The muscles of the body act ordinarily in groups, so that complex movements, such as carrying a spoonful of soup to the mouth, are performed by a number of independent voluntary muscles as if by a mechanism or automaton. The highest point attained by the muscles in this direction is the precision of military drill. In thè disease called locomotor ataxia the muscles that are ordinarily grouped together in their action become slow to act in concert, the want of co-ordination being most obvious in the legs and hips in walking. Progression is not of the usual well-considered kind, but the leg is thrown outwards as well as forwards, and the foot is brought down as if the intention were to strike the ground with it, the knee having been previously straightened. With so little ease are these muscular combinations initiated that the patient requires to look at his feet as if the sense of effect were failing and had to be aided by the sight. Later on the muscles of the upper extremity are in like manner unable to act consentaneously, so that the patient cannot fasten a button, pick up a pin, or the like. Still later there is not only loss of the nicely-adjusted harmonious action among the muscles, but there is a loss of all moderation or graduation in the movements instituted. Whether or not this also be due to loss of the sense of effect, the movement is not adapted to the effect required; it is quick and of short range even when it should be slow and sweeping, and the time and range of the movement of the given limb are practically the same under all circumstances. These errors of the locomotor control are so conspicuous as to have given the disease one of its names; to them we have to add other symptoms varying in the different cases, such as flying pains in the limbs, numbness, squinting and double vision, and functional disorders of the abdominal and pelvic organs. A certain painless structural alteration of the joints (especially the knee), first described by Charcot, is now and then met with, and the remarkable condition known as perforating ulcer of the foot is sometimes found (but not every case of it) to be associated with locomotor ataxia.

The structural changes in the spinal cord begin in the lumbar region and spread upwards; they are in the posterior columns, and especially on their outer limits. Grey degeneration is the name given to the structural condition, and it depends essentially upon the loss of the opaque white substance that invests the axiscylinder of each nerve like an insulating stratum; this layer gives the colour to the white tracts of the cord, and the loss of it reduces these tracts to the grey condition of the central columns of cord where the nerves are normally without the white insulating layer.

The degenerations of the spinal cord, however caused, have little variety; the loss of the white substance may be followed by hardening of the tract of tissue (sclerosis), or there may be a development of the cells of the supporting tissue or neuroglia, keeping pace with the decay of the nerves themselves, whereby the tract acquires a gelatinous appearance. Sometimes the degeneration is not perfectly continuous, but occurs at many isolated spots (multiple disseminated sclerosis).

The causes of the degeneration in locomotor ataxia are various. According to the statistics of Erb, it is nearly always associated with constitutional syphilis; other causes are probably always peripheral somewhere within the region supplied with nerves from the lumbar part of the cord.

The causes of degeneration other than that of tabes dorsalis are also various, and associated with various groups of symptoms, which need not further be considered. Mechanical injury to the cord is followed by degeneration, and the pressure of a tumour may have the same effect. It is found that the solution of continuity of a nerve causes the same loss of the white substance in its peripheral portion as in these degenerations of the cord, and the degeneration of the nerve is set down to its being cut off from its “trophic centre.” The same “trophic” hypothesis is applied to the spinal decay. If the structural degeneration in the cord differs from the degenerations that elsewhere go with disordered function, in its remarkable tendency to spread up or down, that is a difference which may be itself associated with the distinctive conducting function of the nerves and nerve-centres.

In so-called bulbar paralysis, associated with inarticulateness of speech, there is described a certain decay of the ganglion-cells in the nucleus of the hypoglossal nerve, situated in the “bulb” or medulla oblongata, together with general shrinkage of the nucleus; this condition progresses both structurally and functionally towards a more general paralysis.

In infantile paralysis the structural degeneration is found pervading the anterior horns of grey matter of the cord (anterior poliomyelitis), and it includes the ganglion-cells.

Pseudo-hypertrophic Paralysis, Progressive Muscular Atrophy.— These are two closely allied conditions, the one in young children and the other mostly in male adults, which afford the most instructive contrasts. There is gradual loss of muscular power in both, in the case of the children’s malady chiefly in the coarse or static muscles that keep the body erect, and in the nimble and richly innervated muscles of the hand, forearm, and tongue in the progressive muscular atrophy of male adults. In both the loss of muscular power goes hand in hand with a loss of muscular structure; but in the coarse and sluggish groups of muscles which are mostly affected in growing children the loss of muscular structure is more than made up for, in mere bulk, by the development of interstitial connective tissue and fat, while in the nimble muscles of the hand and tongue, chiefly and primarily implicated in the characteristic disease of maturity, there is visible shrinkage of the part. It is only in the limbs, when the affection extends to them, that the bulk and outline are preserved in adults. Hence the affection in children is called pseudo-hypertrophic paralysis, and in adults progressive muscular atrophy. A few cases of great interest have been recorded in which adults have had the two conditions in combination. Children so affected walk as if on tiptoe, with a waddling gait, balancing the body for a perceptible interval on one foot; when they are stripped the dorsal contour is peculiar, the shoulders being thrown back and the belly forward, the calves and hips standing out prominent and hard. In the muscular atrophy of adults the ball of the right thumb is nearly always wasted, and if the other muscles of the hand are equally attenuated there is produced the characteristic appearance of a bird’s claw; the tongue also is often shrivelled.

In contrast to locomotor ataxia, and to paralysis from injury to or pressure on the brain and spinal cord, these two diseases are illustrations of the peripheral relationship of muscle and nerve, of a loss of integrity in that executive relationship, which brings with it both loss of power in the muscle and concomitant failure of its nutrition. They may be quoted as instances of tropho-neuroses, so long as it is clearly understood that the term really explains nothing. There are, indeed, changes described for them in the anterior cornua of the grey matter of the cord, with wasting of the anterior roots of the spinal nerves.

"Dissolution" Principle of Nervous Diseases.— It is known from physiological experiment that a muscle is capable of excitation when the nerve-force is withdrawn from it; muscular substance is not only a contractile form of protoplasm under the control of nerves, but it has proper irritability when the nervous influence is paralysed (as by the action of the curare poison). The condition of the motor nerves in pseudo-hypertrophic muscular paralysis and in progressive muscular atrophy is such that the muscles are left to their indigenous contractility, being deprived of their innervating force. We shall find these two diseases a convenient opportunity of stating a principle in nervous diseases which has been expounded by Hughlings Jackson under the name of the "dissolution” principle. Morbid states of the nervous system (or many of them) are said to be of the nature of a breaking up of the acquisitions of evolution, with loss of the more finished acquisitions, and a falling back to a simpler type, whose unsuitability to the individual in his then general circumstances amounts to a disease. The illustrations already given (§§ 4, 5) of “memories” of development inherent in the cellular life of the body belong to the same class of facts or the same order of ideas.

In applying this principle to the diseases in question we have to consider both the electrical reaction of the muscles and the retrograde changes in their structure. The ‘'reaction of degeneration” is a peculiar one, and it is the diagnostic mark of paralysis of peripheral origin. The degenerated muscle shows a considerable increase of irritability for a time under the galvanic current; the contraction is sluggish and sustained; the anodal closure gives a stronger contraction than the kathodal, while, conversely, the kathodal opening has the advantage. These peculiarities of the electrical reaction in “degenerated” muscles are analogous to the physiological reaction when the nerve-influence has been abrogated. We may take it that a “degenerating” muscle falls back upon its proper irritability, that the contractility becomes “ideo-muscular” as contrasted with “neuro-muscular.” The muscle, so to speak, takes lower ground by way of adapting itself to circumstances.

In the disease in question, as it affects children, the groups of muscles that suffer are precisely those in which the contractility is already of the sluggish, sustained, and ideo-muscular kind,— such muscles as the erector spinae, glutaei, and others, which have an extremely limited nerve-supply in proportion to their bulk. Side by side with this fact we have the other fact of an increase of bulk, as shown in the seemingly strong and hard back, hips, and calves. The paralysis of the muscles has brought with it extreme dilatation of their small arteries, and consequent venous hyperaemia; and this presence of the blood in increased quantity has given an enormous impetus to the growth of the interstitial tissue, in the form of young connective tissue and more particularly in the form of fat-tissue. On the other hand, in the muscular atrophy as it affects adults (mostly of the male sex), it is the very nimblest of all the muscles of the body that are picked out first—the muscles of the right hand—in which the ideo-muscular contractility is naturally small and the neuro-muscular contractility naturally great; and these muscles, with those of the tongue, undergo a remarkable atrophy with little or no spurious compensation from the interstitial tissue. When the disease progresses to other muscles, however, there may be so much new-formed interstitial tissue (fibrous and adipose) that there may be no actual loss of volume in the limb. The precise significance of these differences in the two diseases is not easy to state; in both the males are very much more often affected than the females, being in the one mostly very young boys beginning to walk, and in the other men whose manual dexterity is a formed habit.

The structural changes in the muscular fibre itself are very much the same in both; as the striation of the fibres disappears the quiescent muscle-nuclei become numerous and prominent. The muscle may be said to fall back upon the more embryonic condition, upon the individual life of the cell-units which had been fused in the fibre; it retreats to earlier ground, and, as the proper texture of muscle finally goes, the life of the part takes the still more elementary direction of the common binding-tissue and fat. In this sequence of functional and structural events we may discover an illustration of the dissolution principle. The muscles, having lost, or beginning to lose, their innervation, fall back upon the more primitive kind of irritability; as the downward course of failure proceeds, they retreat still farther to an embryonic structural condition; when the muscle itself is practically lost the commoner forms of mesoblastic tissue take up the retrograde succession; and, last stage of all, even the fat and the fibrous tissue waste. 1

§ 13.— Errors in the Regulation of the Bodily Heat.

The constancy of the bodily temperature under all circumstances of external heat and cold—of torrid and arctic zones, of summer and winter, of sunshine and darkness—is not the least remarkable instance in nature of a self-adapting mechanism. The average internal heat of the human body or of the blood is from 98° to 99° Fahr., and the healthy range in different individuals, or in the same individual at various periods of life, or in various circumstances of exercise and repose, sleeping and waking, is not more than a degree or two below or above the mean. It will be at once apparent that the sensations of heat and cold are no measure of the bodily temperature. The mechanism by which the body’s heat is kept uniform is a co-operation of a number of agencies. It is an equation, of which the two sides are the amount of heat produced in the organism and the amount of heat dissipated. In hibernating mammals the former of these is the side to which adaptation is most directed, in such wise that the whole fires of the animal burn lower while the winter cold lasts. But in man the work and waste go on always, and therefore the heat of combustion is practically uniform at all times, so that the adaptation to seasonal and climatic changes of temperature is mainly on the other side of the equation, the regulation of the amount of heat given off from the body. In cold weather the amount of bodily heat parted with is limited by warm clothing (or clothing which conducts heat with difficulty), by keeping up the temperature of the air artificially by fires, and by the contraction of the surface-vessels and other muscular structures in the skin, which has the effect of diminishing the insensible perspiration and makes the familiar sensation of cold. While these adaptations to external cold are decidedly the greatest, it is not to be supposed that there are no adaptations on the other side of the account. There is, in fact, an increased production of animal heat also, so that more can be parted with, and the constant temperature of 98° - 5 be still unaffected. The increased production is often in the way of increased muscular exercise, which every one is prone to in cold weather; it is to some extent also through the more active circulation in all the internal organs, especially brain and liver, their greater functional activity being attended with a larger amount of the heat of metabolic combustion. A heat-forming diet of carbohydrates (chiefly fats), and the physical benefit of the subcutaneous fat resulting therefrom, are well-known elements of the adaptation in colder latitudes.

When it comes to be an adaptation to great solar heat, the adaptation is again mostly in the way of regulating the heat lost. The vessels of the skin are dilated, and its other muscular elements (in the sweat-glands, &c.) relaxed (making the familiar sensation of heat), so that perspiration flows freely; the evaporation of the sweat on the surface of the body is constantly consuming heat, and the clothing is worn light, and of such colour and texture as will readily conduct heat (both of radiation and of evaporation). There is now as much effort to part with the body’s heat as in winter there was effort to retain it. At the same time the heat of combustion in the body is kept down as much as possible; muscular exertion is avoided, the brain and the digestive functions are less active, and fatty substances are partaken of more sparingly.

The various parts of this conservative adaptation are somehow co-ordinated through the central nervous system. The vascular system is obviously a chief means by which the body’s heat is kept constant, not only by the quick transit of the blood to all parts and the free mixture and

* See Wilks, Lectures on Diseases of the Nervous System, Loud., 18/8; James Ross, Treatise on the Diseases of the Nervous System, 2 vols., 2ded., Lond., 1883; Buzzard, Clin. Led. on Dis. of Nervous Syst., Lond., 1883; Gowers, Epilepsy and other Chronic Convulsive Diseases, Lond., 1881, and Morbid Conditions of the Spinal Cord, 3d ed., Lond., 1884; J. Hughlings Jackson, “Evolution and Dissolution of the Nervous System,” in Brit. Med. Journ., i., 1884.

interchange of its particles, but also by the control of the amount of blood sent to the skin on the one hand (say, in warm weather) and to the muscles and viscera on the other (say, in cold weather). The vaso-motor nervous mechanism, therefore, is an integral part of the nervous control of the bodily temperature. But there is reason to think that the regulation of the bodily heat is committed to the charge of a still higher and more commanding centre in the nervous system than the vaso-motor. It is a remarkable fact, observed from time to time in clinical practice, that certain cases of injury to the brain, from fracture of the skull or internal haemorrhage, are attended with a quite phenomenal rise of the body-temperature—a rise to 107° or 108° Fahr.,—and that, too, when there is nothing strikingly unusual in the vaso-motor effects, as revealed in the skin or elsewhere. In such cases it is the surfaceregion of the pons Varolii, the great cerebellar commissure, that has been injured or compressed by the effusion and coagulation of blood. The evidence of specially-devised experiments confirms and amplifies the clinical evidence; and it is considered in physiology to be a well-grounded fact that there are thermic or heat-regulating centres in the brain, one, at least, being in the region of the pons Varolii. Bernard would further assume the existence of “calorific” and “frigorifie” nerves side by side with vasodilator and vaso-constrictor.

Thermic Fever and Heat-Stroke.— Such, then, being the nicely-balanced and carefully safeguarded mechanism for keeping man’s internal heat about 98° Fahr, under all circumstances, the question arises whether we may trace any considerable part of the sickness and mortality of the globe to a marked and conspicuous failure or break-down of this mechanism of adaptation :—

“But errs not Nature from this gracious end, From burning suns when livid deaths descend?”

Undoubtedly the ardent or thermic fever of Indian practice, the heat-apoplexy, heat-stroke, or sunstroke, is the direct result of an upset or disintegration of the heat-regulating nerve-centre. Either the disorder of innervation is shown in sudden syncope or depression of the heart’s action, as among labourers working or soldiers marching' in the sun; or the effect of atmospheric heat, direct solar or other, is a universal state of venous engorgement, indicating profound vaso-motor paralysis, and ending in death from asphyxia, literally the “livid death” alluded to in the couplet; or the heat-stroke leads to an attack of thermic or “ardent” fever, coming on perhaps in the night within a few hours of exposure, or after a longer interval, having a prodromal stage of malaise, a rise of the body-heat to as much as 108° or 110° Fahr., embarrassments of the lungs and heart, profound brain - troubles, and probably a fatal termination in general venous engorgement and asphyxia. These various forms of heat-stroke all point to a profound disorganization of the nervous centres by the more or less direct action of solar heat,—to cardiac depression in the syncopal form, to more general vaso-motor paralysis in the asphyxiai form, and to disorganization of the thermic nerve-mechanism in the hyperpyrexial form. When recovery takes place, as it does in a large proportion of cases, there are often lasting traces of injury to the nervous system in other functions than the vaso-motor or thermogenic.

These cases of heat-stroke or thermic fever are the most obvious illustrations of a break-down of the heat-regulating mechanism, but they are by no means the most usual illustrations of it. It is in a vastly more common form of sickness, in malarial fevers of all kinds, that we discover the typical failure of the heat-regulating centre under circumstances that tax the self-adapting powers of the body. The enormous prevalence of malarial or climatic fever may be said to be the greatest indication of failure or imperfection in the adaptation of man to his surroundings. In some few spots, which even the'instinct of the brutes leads them to desert for a season, the effects of heat and moisture are such as to induce an endemic diseased habit of body, so universal in its incidence and so insidious in its development as practically to amount to an ethnological distinction (see Heber’s description of villagers in the Terai, Indian Journal, vol. i. p. 251). Throughout the whole intertropical zone, and for 5° beyond it in the southern hemisphere and 20° beyond it in the northern, the climatic fever, in its various forms, stands for almost as much sickness and mortality as all other diseases put together. So stupendous a power has it always been that its pathology has with difficulty emerged from the stage of gross materialism and superstition. But malarial or climatic fever is the true “essential” or “primary” fever of the older writers; its paroxysm is the abstract fever of pathological treatises, which is discussed without reference to communicability from person to person; and, if it has a periodicity which seems to give it specific characters of its own, a little analysis serves to show that its periods of λvaxing and waning are no other than the cosmical periods of the earth itself.

Cullen’s Theory of Fever.— According to Cullen’s theory of fever (which was a modification of Hoffmann’s), “the first incident in the chain of sequences constituting fever is a depressed state of the brain and nervous system; spasm of the extreme capillaries results from this depression; and reaction of the circulation, with its accompanying phenomena, is a∏ effort of the system to overcome the spasm. The Cullenian theory, in a modified form, continues still to be the prevailing creed of those who adhere to the tenets of solidism, and who believe at the same time in the existence of primary or essential fever.” This is the language of Christison in 1840 (Tweedie’s Library of Medicine, vol. i. p. 116); and he adds that the chief rival to this doctrine is one which “denies the existence of any primary or essential fevers, and holds them all to be merely symptomatic of some local disorder.” Cullen did not ignore the differences among fevers in respect of the local condition, exanthematous or other; but his desire for a broad generalization led him to find something common in the antecedents of them all. This was “diminished energy of the brain,” and the nervous depression was caused by “human and marsh effluvia.” When the disentanglements of the century following are credited to Cullen’s doctrine the latter will be seen to be still radically sound. The collocation of “human and marsh effluvia” is nothing but a verbal one; there is no uniformity of effect among human “effluvia” themselves, but rather specific differences; in marsh effluvia nothing has ever been found but common watery vapour; and the characteristic effects of “marsh effluvia” are by no means rare on barren uplands where there is no standing water or decaying vegetation for miles around. The modern disentanglement has put into a class by themselves all the communicable infective diseases which bring more or less of febrile disturbance, and has fixed the attention on the specific features and evolutional antecedents of each. Hence the existence of “primary or essential fever” has come to be denied, except as the abstract febrile state. But it had been forgotten that, for malarial or climatic fevers, there is no communicability, and no specific virus bred in the body or in the body’s discharges; and to them therefore belongs the heritage of “primary or essential fever.” The common aguish intermittent is the source of all the concepts that enter into the doctrine of fever,—the initial malaise, the cold fit and the hot fit, the crisis and the defervescence. It is to it that the classical description of a febrile paroxysm applies, in paragraphs 16 to 23 of Cullen’s First Lines, just as the fever pathology of Hippocrates and Sydenham applies to it; and the first incident in the chain of sequences, according to Cullen, was an “enfeebled energy of the brain.” It will be found that this doctrine of primary or essential fever, understanding climatic or malarial fever therein, is fundamentally in agreement with modem physiological teaching as to the animal heat and the errors in its regulation.

Malarial or Climatic Fevers.— Turning, then, to the analysis of a paroxysm of ague, we find that there is a preceding sense of languor and unfitness for a few hours; all at once the patient begins to feel cold, he shivers, his teeth chatter, his skin becomes “goose-skin” from the poιverful contraction of all the muscular elements in it. If this occurred in the orderly course of regulating the body-heat it would mean that the internal temperature was falling below the mean; the vigorous contraction of tne blood-vessels on the surface of the body is by way of preventing the escape of heat. But the truth is that the body-heat is rising much beyond the normal all the while that the skin is acting so as to keep in the heat. This procedure at cross purposes goes on for a few hours, during which the internal heat may rise to 104° or 105° Fahr. The cold fit passes into the hot, and then the crisis is reached; there is a violent rebound, the muscular elements of the skin and its vessels relax, perspiration flows freely, the kidneys begin to remove all the products of excessive and uncalled-for combustion, and in the morning the patient aλvakes with probably no very serious effects after his feverish night. Assuming the case to be a common quartan, the individual goes to his work next day feeling tolerably well; on the day after he has probably forgotten all about his feverish paroxysm, if it be his first ague; and it is not until the afternoon of the third day that he is again reminded of it. Let us say that he is returning from work towards the end of an ordinarily active day; suddenly he has the same uncontrollable feeling of chills, he shivers, and seeks warmth by crouching over the fire or by wrapping himself in warm clothes. The drama of three days before is repeated, he awakes again from a feverish night, the morning urine being again full of brick-red urates; he now knows that he is the subject of quartan ague, and that another paroxysm is due three days later, which he is fortunately able to prevent or at least to mitigate by taking quinine in the meantime. Whatever may have induced the first paroxysm, the second is a mere imitation of it, an affair of habit, just as a return of an epileptic con vulsion is. It can hardly be doubted that in the repetition of a simple ague - paroxysm we are concerned, not with the nervous system as co-ordinating the two sides of the account in the production and discharge of animal heat, but with an acquired habit of the nervous system, with a usurpation of the power committed to it for the purposes of control only. This acquired faculty of the heat-regulating centre to act quasi-autocratically is often exemplified in those persons who, having suffered from malarial fever under its usual exciting circumstances, experience a return of it under widely different circumstances. Thus, a pronounced ague-shake has occurred to a person crossing an ice-slope 10,000 feet above the sea-level, the original ague having been contracted several years before in a malarious locality.

We come next to the circumstances under which the heat-regulating centre suffers this disorganization, the memory of which may remain with it for long after. The circumstances of intermittent and remittent fevers have been already discussed in the article Malaria, and it remains to give here only a brief epitome. Where-ever and whenever malarial fevers occur there are considerable degrees of solar heat and of moisture in the lowest stratum of the air, and a considerable drop of the temperature after sunset. So far as the individual is concerned, he incurs risk by working in the sun and resting or sleeping in the chill of the evening, by letting a wind such as the monsoon blow upon his fatigued body, by passing suddenly from the relaxing conditions of heat to the constricting conditions of cold, by arriving from cooler latitudes in the hot season, and by doing one or all of these things when his nervous power, as Cullen said, is enfeebled by such causes as anxiety, intemperance in drinking, “and other circumstances which evidently weaken the system.” A high degree of moisture in the lowest stratum of the air is the most universal of the external factors within the malarious latitudes, and it may be produced either by the extreme dampness of the soil or by the extremely rapid cooling of a dry soil (even bare rocks) by radiation of heat after sunset, whereby a moderate degree of atmospheric moisture gives a fall of dew. On the other hand, wherever the atmosphere is exceptionally dry, as on the southern littoral of Australia, there is no malaria notwithstanding the great solar heat; and wherever there are only a few degrees of difference between the day and night temperature and a very slight range throughout the year, as at sea within the tropics, or at such localities as Singapore and the Amazon valley under the line, malaria is far less active than the great solar heat and moisture might lead one to expect. Whatever’ in the telluric and atmospheric surroundings taxes the nervous mechanism which keeps the heat of the body always about 98° or 99° Fahr, is a cause of malarial fever.

The Cold Fit of Fever.— The central point of interest in a paroxysm of fever, the grand paradox of fever-pathology, is the rise of the heat ρf combustion, as shown by the clinical thermometer, and the simultaneous closing of the natural outlets of excessive heat, as shown by the shivering and the feeling of “goose-skin.” The value of any pathological doctrine of intermittent and remittent fever may be estimated by its success in dealing with this paradox. We may conveniently approach this subject through the following concrete instance, as given by Oldham. “At Jhansi, in June 1860, a young officer of the battery of artillery to which I belonged was exposed for some time to the sun at mid-day; he then, in a profuse perspiration, came into the house, through which a hot wind was blowing, as all the woodwork had been burned by the rebels, and the tatties, which served for doors and windows, were almost dry; in a few minutes he complained of being chilly, and in a few more he was in the cold stage of a sharp attack of intermittent. This officer had never previously suffered from fever; when he went out a short time before he was in perfect health, and he had not, whilst away, been into any malarious locality; in fact, at that season, the whole country round was parched and dry.” This case illustrates an important point,—antecedent exposure to great solar heat. Exercise in the sun means active internal combustion in the muscles, liver, &c., and the body warmed at the same time by the sun’s rays; the equalizing of the heat made and the heat lost is accordingly a difficult task, which falls mostly on the skin (and lungs) to execute, and the heat - regulating centre to order and control. We may take it that both the regulating function of the nerve-centre and the executive function of the skin are strained to the utmost. In the case quoted, where there was no interval between the cause and the effect, the body in its glowing state is suddenly exposed to a slight abstraction of heat through the draught in the house; the sudden loss of heat, however slight the amount, is the signal for the skin to close its pores so as to lose no more heat, and hence the passing feeling of chill. But the passing feeling of chill is in this case succeeded, at only a few minutes’ interval, by the prolonged state of contraction of the cutaneous vessels, sweat-glands, and other muscular structures which corresponds to the rigors and the cold fit of ague; and, all the while that the skin is thus vigorously adapting itself to prevent the escape of heat, the heat of the body is rising several degrees. The skin and the nervous centre, the executive and the central authority, are at cross purposes so far as the object is to keep the temperature at the level of 98° or 99° Fahr. Now, the rise of temperature in this case can have had no other source than internal combustion (in the liver, muscles, brain, &c.); but the combustion is an unnatural one, inasmuch as no proper physiological work has been got as its equivalent out of the muscles, brain, or liver, although there has been the due physiological waste (carbonic acid and urea). A slight chill, or the sudden abstraction of a not very large amount of heat from the surface of the body, has excited the heat-regulating centre in such a way that it lets loose an extravagant amount of its “thermogenic” force. The nervous centre has been called upon to equalize the slight abstraction of heat at a moment when it is still in the state of strain from its previous and well-sustained efforts to keep the balance, and it is upset by the sudden call. It answers by an altogether disproportionate discharge of its force, which is both ill adapted to the momentary needs of the body and continues in operation much beyond the occasion for it.

Under ordinary circumstances of taking the ague there is usually an interval between the exposure to heat and the exposure to chill. Usually, also, the exposure to heat is more or less prolonged or habitual; the heat-regulating centre is taxed over and over again, and it is taxed so much the more if there is moisture in the air along with solar heat, the dissipation of the body’s heat by the insensible perspiration and by radiation being much more difficult in a damp atmosphere than in a dry. Whenever the chill comes, it finds the heat-regulating centre without that tone which would enable it to act according to the emergency, so that the abstraction of heat, even if it be slight, is the signal for an enormous stirring up of all the internal fires and a rapid combustion to meet a loss of heat which is not greater than the body endures under other circumstances with impunity. This phenomenal burst of heat-making is, so to speak, misunderstood by the motor nerves of the skin; whenever, under the same circumstances of repose, there is the same thermogenic activity, it means that the heat is wanted to keep up the level of 98° or 99° Fahr., and all the muscular elements in the skin and in its vessels contract to keep the heat in, producing the feeling of external cold, or of shivering if the contraction be extreme. The same thing happens under the incoherent and extravagant action of the heat-regulating centre; and hence the paradox of the body shivering all the while that its internal heat is rising to 5° or 6° Fahr, above the average of health.

Another way of expressing the paradox is to employ Bernard’s language of “thermic nerves”; we should then say that stimulation of “calorific nerves” goes with a stimulation of “vaso-constrictor” nerves in the skin, so that a violent discharge of force along the one path is associated with a violent discharge along the other. Whether, as Traube has suggested, the extravagant action of the heat-regulating centre might be altogether counteracted by the usual heat-discharging mechanism but for the inopportune constriction in the cutaneous vessels and the surface of the body generally, is a curious question, but hardly a practical one. In that degree of shock to or disorganization of the nerve-centre which occurs in ordinary tertian or quartan intermittent the duration and degree of the shivering fit are the index of the mildness of the attack; the more pronounced the cold stage, the more prompt is the crisis and the more certain the defervescence. But in the much more severe shock which brings a quotidian or a remittent, the cold stage is short and feeble, and the crisis and defervescence are proportionately undecided and uncertain. The remittent degree of climatic fever approximates, indeed, to the forms of continued fever in which the rigor is a mere survival of the great cold fit of intermittent; the initial rigors even of pneumonia are little more than formal, apd the hot stage of the process is practically the whole. It would thus appear that the vaso-motor constriction, upon which the phenomena of the cold fit depend, is the due accompaniment of a certain moderate degree of upset in the thermogenic nervemechanism; the paradox of the body shivering while its internal heat is rising is after all a paradox, and not an antagonism. The severer types of climatic fever are those in which the primary shock has been most severe or least well sustained. “Degrees of fever,” says Ferguson, “might be almost measured by degrees of solar heat, from the agues of Lincolnshire to the malignant remittents of the West Indies.”

The periodicity of agues is a reflex of the normal periodicities of the bodily heat; in health the temperature rises to its highest point in the course of the afternoon and falls to its lowest a little after midnight, and in a typical intermittent these are usually the hours when a paroxysm begins and ends respectively. These normal maxima and minima of the body’s heat within a diurnal revolution are probably in their origin an adaptation to the periods of labour and rest, both muscular and digestive; but the habit is an ingrained one, and it obtains when the ordinary round of work and repose, of waking and sleeping, is departed from. In short, it follows the sun and not the vicissitudes of human occupation. Again, the periodical recurrences of the febrile paroxysm appear to follow the lunar intervals. In the United States an ague is observed which has on!y a weekly paroxysm; the quartan of northern latitudes is the bi - weekly interval. Tertian and quotidian agues would not of themselves suggest lunar periodicity, but they are related to the types with obvious lunar intervals. The “critical days” of continued fevers, which were closely observed in former times, have been brought with much ingenuity under a law of cosmical periodicity. It is observed in climatic fevers that, if there be an interval of one or more weeks in which the paroxysms are in abeyance, the next succeeding paroxysm will occur at its due time, and that various minor indications of constitutional disturbance in the interval (perhaps neuralgias) will have marked the periods when the full paroxysm should have developed.

It is necessary to pass over the changes in the blood and in the secretions which accompany the febrile paroxysm. In ague there is a remarkable production of free pigment traced to the red blooddisks, which accumulates in the spleen, the bone-marrow, and elsewhere. The spleen undergoes also an enlargement, and so does the liver; these are permanent where the malarial cachexia exists. The malarial cachexia, marked by hydraemia and lassitude, occurs most frequently in those who reside on a waterlogged soil, and are permanently subject to the difficulties of heat-regulation during their work which an atmosphere saturated with watery vapour entails. In such cases there may be no febrile paroxysms from first to last, but a state of adaptation of the body which is at once a disease and almost an ethnological character.

Dysentery. — It is universally admitted that the causes which produce intermittent in one man of an exposed party may produce remittent in another, dysentery in a third, and abscess of the liver in a fourth. The incidence in the form of dysentery is apparently capricious; we have simply the fact that, in a certain proportion of cases, the shock resolves itself into a profound disorganization of the function of the great intestine, which may pass off in a few days or become chronic. The dysenteric seizure is most frequent where there is extreme atmospheric moisture as well as extreme heat, and where the surface of the body is most directly exposed. The region of the loins is somehow a region of great liability, just as the head is, the turban or pith helmet and the loin-cloth of hot countries being the indications of these liabilities. One important point of difference between dysentery and intermittent and remittent is that the former disease runs its course in one attack, whereas in the latter there is the remarkable habit of repetition. The return of the ague paroxysm is an evidence that the disorder is fundamentally one of the nerve-centres; it is an instance of the “memory” or “habit” which disordered nerve-mechanisms are peculiarly apt to fall into and to retain. In dysentery the disorder is localized; it is not so much central as peripheral. Whoever has had dysentery once is apt to have it again, and it may become chronic from the first seizure. But it has obvious points of difference from climatic fever, and these differences are associated with the localized incidence of the primary disturbance.

Dysentery may arise under other circumstances than exposure to tropical heat and moisture and to tropical chill, as in Avars and famines, in cold, and amidst privations and overcrowding. In such cases it is correlated rather to typhus fever than to malarial, but it is probable that there is the same kind of primary effect produced through the nervous mechanisms as when the vicissitudes of a tropical climate are the cause. Again, the dysentery of slave-ships (formerly) and of coolie-ships (at present), in tropical waters, would appear to be a mixed effect.

The effluvia from dysenteric dejecta (or water contaminated by the dejecta) appear to have the power of exciting, in persons who have not been directly exposed to the causes of dysentery, either dysentery itself or some vicarious infection, such as typhus fever or yellow fever, according to the source of the dejecta, or the kind and degree of putrefaction which they had undergone, or according to racial differences in the exposed persons. This question belongs to another part of the subject.

Tropical Abscess of the Liver.— This is intimately associated with dysentery in its causation; it may be either a primary effect, as it were, instead of dysentery, or it may be an after-effect of one or more attacks of the latter. The primary effect has been dwelt upon by some, and the after-effect by others (notably W. Budd), but there is really no antagonism between them. As a primary effect tropical abscess of the liver is closely parallel with tropical dysentery and with malarial fever. It is not the effect of heat by itself, but of chill as the sequel of great exposure to heat. Solar heat is trying to the hepatic function, there being an increase of bile; when the organ has been thus overtaxed it is sensitive to the vicissitudes of heat and cold. It is pointed out by Dr James Johnson (The Influence of Tropical Climates, p. 177) that genuine hepatitis is even more frequent in the Carnatic, with uniform but high temperature, than in Bengal with a more variable and damp climate. “The casual visitor may well wonder how cold can be often applied on the burning coast of Coromandel, where the temperature is high and steady by day, where the nights are, for months together, hot, and seldom raw or damp as at Bombay or Bengal. . . . The European soldier or sailor, exhausted by exercise in the heat of the day and by profuse perspiration, strips himself the moment his duty is over, and throws himself down opposite a window or port to inhale the refreshing sea-breeze, his shirt in all probability dripping with sweat,” and the consequences are likely to be an attack of hepatitis or abscess of the liver. A slight abstraction of heat completely upsets the organ which had been most taxed under the particular climate; the incidence is not so much upon the heat-regulating central government as upon a most important member of its executive. As the sudden abstraction of a small amount of heat from a fatigued and perspiring body can produce an extravagant discharge of heat-producing force, or a paroxysm of fever, by touching ’ the nerve-centre, so it can produce a peripheral effect in the most important of the heat-forming organs, which had under the special circumstances been overtaxed in its function. But the effect on this peripheral part of the heat-producing mechanism is not, for the most part, an increased production of heat as in fever; it is, in fact, local congestion of blood and suppuration. When the strain falls on the central government the effect is fever; when the strain falls on an important member of the executive the effect is inflammation.

Pneumonia.— Congestion of the lungs and pneumonia are not unfrequent accompaniments of remittent fever in India, especially in those whose health had been previously enfeebled, and among the more ill-clad natives. Pneumonia is liable to occur in those who had been acclimatized to heat, on their exposure to unusual degrees of cold, as among the negroes in the United States. It has been also observed to become widely prevalent, and in a form which amounted almost to pneumonia pure and simple, among the troops from India employed in Afghanistan in 1838-39, and again in 1878, when they were exposed to the winter cold.

Pneumonia is indeed an effect of chill proper to higher latitudes, just as intermittents and remittents, dysentery, and hepatic abscess are most characteristically the effects of disorder, either central or peripheral, in the heat-regulating mechanism as adapted to tropical and sub-tropical conditions. That pneumonia is nearly always caused by chill is generally believed (the pneumonias of contagious origin being excepted); but it may not be so readily admitted that we have here to deal with a disorder of the heat-regulating mechanism. Pneumonia is, at all events, a fever; it has an initial period of rigors, more pronounced than in most continued fevers, although far behind the cold fit of intermittent; the pyrexia is sometimes present for some hours before the other symptoms become marked; it usually comes to an end abruptly some time before the consolidation of the lung is all cleared up; and that crisis in the disease is apt to fall within a week of the onset, and is seldom delayed more than a day or two over the week. The stress of this disease falls upon the lung, usually upon one lung, and more particularly upon the lower half of the lung. Leaving, for the present, the question why the lung is in this case the organ of metabolism upon which the stress falls, let us consider the nature of the pulmonary condition.

First, there is engorgement of blood, a condition which is due, according to all analogies, to paralysis of the vaso-motor nerves. The abundant capillaιy vessels round the air-cells are greatly distended with blood, and the mucous membrane of all the bronchial tubes is also much injected. Accompanying this state of the pulmonary circulation there is more or less obvious distress of breathing, or dyspnoea, together with a strong, full, and quickened action of the heart. If the action of the heart be weak and the distress of breathing great it is a sign that the shock has been more severe than the patient, as he is then circumstanced, can stand, and death may result merely from congestion of the lung. Usually the extreme congestion of the vessels is relieved by exudation from them into the air-cells which they surround; if the patient should die at this, the second stage of pneumonia, the lung, or lobe of the lung, is found to be solid enough to sink in water; it is still red, as in the stage of engorgement, but the cut surface is firm, and under a lens looks to be finely granulated. Each little granule corresponds to an air-cell, the air-cell no longer containing air, but a solid coagulum consisting of numerous threads of fibrin, with a homogeneous plasma as the basis, and a few red blood-disks and white blood-corpuscles (fig. 55). The whole of this is an escape from the overloaded blood-capillaries. The lung is just one of those organs where such an escape from the blood is possible; the engorged vessels are distributed as a plexus over the thin walls of air-filled spaces, and the fluid part of the blood, together with a certain proportion of its solid particles, passes through the walls of the vessels into the airspace. If the lung be examined from a case of pneumonia fatal a day or two later, or in the third stage, it is still solid, but the redness is mottled with grey, or has become uniformly grey. The number of round nuclear cells in the air-vesicles has increased enormously, usurping the place of the fibrin and plasma (fig. 56). There is no good reason to suppose that this enormous accumulation of cells is due to successive additions of colourless corpuscles from the blood; they are now, many of them, much larger than the blood-cells, and we may take it that they are the product either of subdivision of the few original blood-cells or of the epithelium of the air-vesicles. The solidity now begins to give way, the contents of the airvesicles undergoing a mucoid or other disintegration, and they are gradually removed for the most part by expectoration. In ten days from the onset the lung may have returned to its normal condition.

We have now to consider briefly this disease as an error in the heat-regulating mechanism, in which the strain falls upon an important peripheral or executive part. Hepatitis may be taken to be this kind of effect where the chill is a slight abstraction of the body’s heat under tropical conditions; pneumonia is this kind of effect where the chill is caught under the vicissitudes of the weather in spring, or in changeable weather generally, within the temperate zone. Why should the liver be the organ of choice in the one case and the lung in the other? It may be said at least that each organ, in the respective circumstances, is the locus minoris resistentiae. A sudden abstraction of heat is a strain or shock to the heat-regulating centre, and, if the incidence is to be on the executive, it will fall on that member of the executive whose function had been, under the circumstances, most taxed. It is to be remarked that such cases of so-called peripheral incidence are associated with individual predisposition; hence these diseases are generally sporadic. Something in the antecedents of the individual has determined the local character of the effects of chill, whereas the great climatic fevers more uniformly befall those who expose themselves.

Rheumatic Fever.— Rheumatic fever is universally admitted to be an effect of chill. “I know of no other exciting cause of acute rheumatism,” says Watson, “than exposure to cold, and especially cold combined with moisture.” The conditions, both external and predisposing in the individual, which constitute the peculiar liability to rheumatic fever are nowhere found more distinctively than in the variable climate of the British Islands, and in the habit of body of the people. It is especially a disease of early manhood and womanhood, and of the working class; when it occurs before puberty it is associated in a remarkable way with the liability to chorea.

The onset of the fever is preceded for a few days by general ill health, chilliness, furred tongue, “break-bone” pains, flying pains in the joints, some quinsy, and disturbed sleep. If these symptoms proceed no farther, the patient would be judged to have had a chill, a catarrhal attack, a quinsy, or the like. When the initial upset has been more considerable the pains “settle” in one or more of the larger joints, often the ankles at first, the knees subsequently, or the wrists, elbows, and shoulders. The patient lies flat on his back, not daring to move, and following the objects around with his eyes only. Profuse sweats break out from time to time, having a peculiar acrid smell, by which rheumatic fever can even be diagnosed. The joints where the acute pain is seated for the time being are swollen, tender, and often red and hot, the swelling being either in the fibrous structures around the joint or in its synovial cavity. The locale both of pain and swelling shifts from joint to joint; the disease often “flies to the heart” (pericardium and endocardium), more rarely it “flies to the brain” (membranes). The urine is scanty, high-coloured, depositing brick-red urates, and with an excess of urea on analysis; it is, in fact, the urine of disordered heat-regulation. The temperature is 100° or 101° up to 104° or 105°, and in some exceptional cases (of “hyperpyrexia”) rising to 109° Fahr. There is an afternoon rise of 1° or more, and a corresponding fall in the night. The severity of the case —apart from its danger, which really depends on the pericardial or endocardial part of the disease, or on complications with pneumonia and the like—is measured by the height of the temperature, with which, again, the intensity of the pain in the joints goes hand in hand. The outbreaks of sweat do not follow any obvious law, and they are not “critical,” as in intermittents; but they seem to give the patient relief for the time, even if they leave weakness behind. Nine days is considered an average time for such an attack to run its course if the patient be well cared for; but defervescence is gradual, and complete restoration to health is often slow, much weakness and anaemia remaining to be made good. Warren, a physician of a former generation, when asked what was the best remedy for rheumatic fever, answered “Six weeks.” Relapse is not uncommon, a very slight chill or sudden abstraction of heat sufficing to bring the fever back.

Now if we assume that the occasion of an attack of rheumatic fever is chill—that is to say, a sudden shock or injury to, or disorganization of, the nervous centre which presides over the uniform body-temperature—we enter upon a profoundly interesting problem in following out the constitutional manifestations. Everything points to the mechanisms of locomotion, to the structures and surfaces where muscular work is applied; even the heart, as Watson remarks, is in its perpetual to-and-fro movement comparable to “one of the large joints.” There is heat of combustion from some source or another to account for the rise of temperature, which is sometimes enormous; but it is not the heat of work done. λVe are again confronted with that most fundamental of all the questions relating to fever, the question, as stated by Foster, whether the “metabolism of even muscular tissue might be influenced by nervous or by other agency in such a way that a large decomposition of the muscular substance, productive of much heat, might take place without any contraction being necessarily caused . . . in such a way that all the energy set free would take on the form of heat.” Is rheumatic fever one of those cases where disorder of the heatregulating mechanism falls on an important member of the executive, namely, the muscular system, just as it falls on the liver in tropical abscess, and on the lungs in pneumonia?

Certainly we know of no muscle but the heart itself which shows appreciable structural changes in rheumatic fever; the heart is liable to “myocarditis,” as well as to endocarditis and pericarditis, but, for all other muscles, the changes are in the tendons, ligaments, and synovial membranes only, or, in fact, in those structures by which the work of muscles is applied. These structures have nerves, some of them large enough to be looked for in the dissecting-room, although less is made of them in physiology. The function of the nerves of the joints is not sensory in the ordinary use of the term, but it may be said to be to convey to the centres the sense of effect of the work done by muscles. When there is intense metabolism of the muscular substance, but no work done, the same nerves, having no sense of effect to convey, convey an acute sense of pain. The pain of rheumatic fever is altogether more acute than in inflammations. In tropical abscess pain is subordinate, and its place is taken by a vague feeling of trouble, or tightness, or weight, or heat in the hypochondrium, and the same substitution is sometimes made for the pain in pneumonia; but in rheumatic fever pain may be said always to be the grand symptom, and a measure of the very remarkable power of recovery. Reversing the maxim which applies to tropical abscess and to the worst cases of pneumonia, we may say of rheumatic fever: “Affert plus doloris quam periculi.”

Sweating is the other grand symptom of rheumatic fever. It can hardly be said to be critical for the disease as a whole, because the temperature does not fall; but the joints affected for the time being are relieved by it, and it is critical to that extent. We may, indeed, say that the temperature does not fall because the heat goes on being generated in some other group or groups of muscles in whose joint or joints the pain is next felt.

We may regard, then, the sequence of events in rheumatic fever somewhat as follows. There is an upset of the heat-regulating centre by chill, owing to which an extravagant amount of heatgenerating nerve-influence is sent out; this falls, for some reason of the body’s habit (inherited or proper to the individual’s occupation, or otherwise special), upon the muscular system, whose metabolism produces heat without work; the articular nerves which are ordinarily employed to convey the sense of effect of woιk done, from the surfaces where the movement is applied, convey, under the changed circumstances of the muscles’ activity, a sense of pain. One set of muscles after another generates heat without work, so that one joint becomes painful after another; and, although there are perspirations by which the heat of the body is parted with, other sets of muscles take up the work of combustion in their turn, so that the excessive temperature is maintained. Among other muscles the heart is affected; and, just as in the voluntary muscles the structural effects are in the synovial membranes, ligaments, tendons, and aponeuroses, so in the heart they are in the pericardium and in the more fibrous parts of the endocardium. But they are sometimes in the cardiac muscular tissue itself, the muscular substance of the heart being peculiar.

The association ιvith chorea may now be noticed. Chorea is not a disorder of heat-regulation, and it is not due to chill; it is a disorderly habit of some nervous centre or centres whereby the ordinary work of muscles is made irregular, and it is due to some feebleness in, rather than to injuιy of, the nervous mechanism. The considerable liability of choreic subjects to rheumatic fever, the actual endocarditis that they suffer from even if they have never had rheumatic fever, the occasionally observed choreic movements of the muscles in the course of true rheumatic fever in adults, the occurrence of chorea as a sequel of rheumatic fever —all these associated things go to show that the disordered nerve-centre is the same in both diseases, and that the discharge of its force may pass readily from one path to another. It may either set free muscular heat without muscular work, excessive in degree and attended by unique pain in the joints; or it may spend itself in those gratuitous displays of muscular work rvhich amount to chorea.

The foregoing diseases have been regarded as errors of the heatregulating nervous mechanism. In rheumatic fever we have seen that there is a singular relationship to a truly nervous disorder, namely, chorea. It remains to mention another implication of the nervous system which several of them have in common, namely, an herpetic eruption about the corners of the mouth. Herpes is now accepted as an affair of certain cutaneous nerve-areas; and in malarial fever, pneumonia, and acute attacks of quinsy due to chill there are very apt to be eruptions of herpes labialis. Why the labial region should be involved is not obvious.

§ 14.— Inflammation.

The inflammations may be regarded as an empirically made-up group of disordered states which have somewhat in common. Although inflammation is certainly a provisional category, there has always been a tendency to overcrowd it with newly-described morbid conditions, rather than to empty it of its temporary occupants. Whenever pathologists have become impatient to say the last word about the endless perplexities of disease the class of inflammations has become unusually full; this happened in the period of Broussais, when even the specific infections were placed therein, as gastro-enteritis and the like; and the frequent resort to the termination itis in more recent pathology may be taken as an evidence of a corresponding habit of mind. Thus there is much fairness in the bold criticism of Andral: “Reçu dans le langage, sans qu’aucune idée précise lui ait jamais été attachée, sous le triple rapport des symptomes qui l’annoncent, des lésions qui la caractérisent, et de sa nature intime, l’expression inflammation est devenue une expression tellement vague, son interpretation est tellement arbitraire, qu’elle a réellement perdu toute valeur; elle est comme une vieille monnaie sans empreinte, qui doit être mise hors de cours, car elle ne causerait qu’erreur et confusion.” It is at least the duty of pathology to reduce the congeries of inflammations to as small a bulk as possible, to follow up the analysis of the inflammations one after another until they are reduced to the scientific position of errors of the respective structures and functions. Inflammations, indeed, are best regarded as an ever-diminishing residue; there is always the residue, because the correlated structural and functional aspects of the life of the tissues cannot be stated with equal clearness for all of them. It is the great binding tissue of the body that gives occasion for this nosological residue; the connective tissue is the one tissue about whose dual life of structure and function there is a difficulty. We shall appreciate its unique position best by comparing it with so direct a modification of itself as fat-tissue. But even these phlegmasiae are capable of some further analysis in the direction of disordered structure and function if we have regard to the functions of the embryonic mesoblast, and to the “memories” of the same that the common binding tissue never quite loses.

The earliest and most fundamental notions about inflammation, and those which pertain to the residue above spoken of, were derived from the external parts of the body when injured by blows, wounds, scalds, the lodgment of foreign bodies, and such-like palpable irritations. Along with simple inflamed wounds were taken cases of erysipelas, a disease which has now become the sole heir of the original Greek name for inflammation, namely, phlegmon. It -will be convenient to begin with a brief reference to erysipelas.

Erysipelas.— Besides phlegmonous erysipelas, or diffuse inflammation and suppuration of the cutaneous and subcutaneous connective tissues, there is a common form consisting of redness, swelling, pain, and heat of the surface only, and stopping short of suppuration.

This condition often follows a wound, especially in the region of the scalp or face; it may occur also when there is no obvious wound, although there will probably have been a catarrhal state of the nearest mucous membrane. Fever or constitutional disturbance usually precedes the inflammation twenty-four hours or less, and in this respect erysipelas is comparable to the effects of chill already treated of. Wounds received in a drunken brawl are especially apt to become erysipelatous; also the wounds of those suffering from kidney-disease or liver-disease. Erysipelas is most apt to occur in cold weather with east winds, or in cold and damp weather. One attack predisposes to others. It often arises spontaneously or autochthonously, but it is perhaps equally often induced by contagion and inoculation from pre-existing cases. Of its origin de novo from time to time there need be no question; thus, it has been observed in a single individual of a ship’s company at sea off Cape Horn. The redness and swelling advance with a well-marked border from the wound or other starting-point until they have invaded, it may be, a large cutaneous area. There is exuded plasma in the spaces of the connective tissue, and there are also nuclear cells (leucocytes) in the lymphatic spaces and vessels, and in the tissue generally. An increase of the colourless cells in the blood is also described. Since attention has been called to the presence of minute living organisms in disease there have not been wanting authentic descriptions of micrococci in the lymphatic spaces of the advancing margin in erysipelas, although they are said to be absent in the older areas of the inflammation, and during the stage of subsidence generally.

In phlegmonoιιs erysipelas the connective tissues to a considerable depth beneath the skin are soaked in serous fluid, which becomes turbid, like thin pus; at a later stage the lines of pus extend in all directions along the tracts of binding tissue, fragments of the latter being found as detached shreds in the larger purulent centres. The skin, usually of a limb, may thus become involved over a large area and to a great depth, considerable pieces of tissue falling at once into a state of slough. The temperature is often as high as 105°, and delirium, with other symptoms of nervous disorganization, is common. Death from failure of the heart is probable. This disease is the most extreme form of phlegmon, by far the most formidable inflammation that exists. It is usually the sequel of a wound, but not invariably. Chilliness and all the other symptoms of commencing fever precede the local phlegmon, so that the condition is comparable to those errors in the regulation of the animal heat, previously mentioned, in which the incidence falls upon a peripheral part. That it is itself a local effect of general temperature disorder cannot be maintained, inasmuch as there is usually nothing in the antecedent circumstances to implicate directly the heat-regulating centre. However, it is not the extent of the local injury that serves to account for the inflammation, but the habit of body of the patient, especially the drinking habit. It is not an overtaxed heat - regulating centre that is implicated, but a nervous system overtaxed in more general respects. A peripheral injury, not necessarily a severe one, tells in an unusual way upon the unstable centres, just as in tetanus; and the outgoing response falls in a peculiar way or with a peculiar force upon the wounded part, producing phlegmon there and fever generally. Whether the rise of the body - temperature is mainly due to over-combustion within the injured area is open to discussion. The connective tissue as a source of heat has not hitherto come into our consideration; if it is to be regarded as a member of the heat-producing executive, under the central nervous control, its membership is at least not important except when the redness, swelling, heat, and pain of inflammation are present.

The same state of the tissues as in phlegmonous erysipelas is brought about, all but the redness of the surface, by a very different cause—the introduction of a minute quantity of venom, either the cadaveric venom introduced in a dissection-wound or the venom of the rattlesnake and adder. The bites or stings of many other animals produce more transitory inflammatory effects.

In common inflammation, such as follows the lodgment of a spicule of broken glass under the skin of the hand or arm (to borrow Watson’s illustration), there is first pain; soon there is redness around the point of entrance, with swelling and heat; the skin becomes of a bright-red colour; the swelling increases, becoming hard and firmat the centre of the inflamed area, and exquisitely tender, or painful to the touch. If these local effects are at all considerable (according to the nature and extent of the injury, and to the susceptibility or habit of body of the individual) there is inflammatory fever some hours later. At first there is usually chilliness and feebleness, then there is a general feeling of heat and dryness, with a quick, full, and hard pulse, headache, wandering pains in the limbs, restlessness, some mental confusion, disturbed sleep, a white tongue, thirst, and loss of appetite. If the piece of glass be removed all these symptoms, local and general, may subside quickly. If the source of irritation remain, or even, notwithstanding its removal, if the primary shock has been severe, the symptoms continue and intensify. Relief to the constitutional disturbance comes with the further developments in the injured area—with suppuration or, at the latest, with the bursting or letting out of the matter. Healing then proceeds as described under “repair.”

This is the usual sequence of events in common inflammation, in the inflammation of moderate degree in a healthy person. It differs from erysipelas or phlegmon in the important respect that the fever follows the local effects at an interval of several hours. Where the injury is of the most violent kind, as in some machinery accidents, neither the local effects nor the fever are pronounced; the “reaction” is said, to be in abeyance, and death is apt to occur from shock. In these cases the face is blanched, the action of the heart and lungs feeble, and the mental faculties profoundly oppressed; the presiding control has been so upset by the injury to even a limb that the forces of the body do not rally.

The heat of an inflamed part is not merely in the feelings of the patient; it is actually several degrees (up to 6° or 7° Fahr. ) higher than the temperature of the part in health or of the corresponding part on the opposite side, although it is never above the central blood-heat of health. It is not solely dependent, therefore, on the general state of fever. Neither can it be said that the general state of fever is solely dependent on the increased local combustion. In erysipelas, as we have seen, the general fever usually precedes the local, and must depend upon some general error of heat-making. Again, in a common inflamed wound, the general fever may, and usually does, subside some time before the cellular changes in the part, degenerative or formative or both, have passed their climax.

Implication of the Nervous Control in Inflammation.— From slight inflammations, with little more than redness and pain at the seat of injury, to the most shattering strokes there is a succession of steps. The nervous system is implicated in them all, for the reason that the nerves are everywhere, and everywhere ready to transmit impressions to the centre. It is not surprising, then, that in every doctrine of inflammation since the time of Cullen the events have been largely traced to the direct action of the nerves and nerve-centres. Amidst all the conflicting views taken of the nature of inflammation in current writings, there is agreement on this point at least, that the nervous control has much to do with it,—if not always the central control, yet some local control whose existence would hardly be suspected but for the phenomena of inflammation. The differences of opinion begin when we come to the details of the nervous control. Does the nervous system preside over the action of the vessels only, or does it preside over the whole cellular life or the nutrition of the part? Opinions have had a tendency to range themselves on two sides, corresponding in the main to the more mechanical or to the more “vitalist” conception of life as a whole. The afflux of blood, which every one recognizes as the first conspicuous event in an inflamed part, has been attributed in the latter view to an attraction exercised by the cells of the part, to a hunger for blood comparable to that which causes a determination of blood in an organ that is going to be physiologically active. “The facts,” says Alison, “afford a strong presumption that the impressions made on the capillaries, and on the blood contained in them, solicit the flow through them on the principle of a vital attraction of the blood rather than of relaxation of the vessels.” This is the “solicitation of fluids,” the “movement of turgescence” or the “vital erection of vessels” of the older authors. If the needs of nutrition are the ordinary attraction, they may be simulated by such incidents as wounds, scalds, and the like; and it is the peculiarity of inflammation that the incidence of these is on a tissue whose physiological interest is ordinarily of little or no account, namely, the common binding tissue. It is with justice that Rindfleisch emphasizes the intimate connexion between the common binding tissue and the peripheral nerves and nerve-plexuses. “They run exclusively in the connective tissue; in it they divide and form plexuses, which ultimately join, without any definite demarcation, with the network of connective-tissue corpuscles. Their distribution in the connective tissue designates these nerves for some definite function; they are admirably adapted to play a part in the general physical and chemical changes of the organs, to give information of the same to the central nervous system through their corresponding states of excitation. With the connective tissue they participate in the most intimate structure of organs, with the connective tissue they are stretched and pressed upon, with it also they suffer those chemical excitations which any considerable accumulation of waste matters brings with it.” Now, it is known from numerous experiments that, if a nerve of common sensation be stimulated, the outgoing response from the centre is by way of removing the tonicity of the arteries of the part, so that they dilate and transmit much more blood. This outgoing influence is assumed to travel by a special set of fibres called, for convenience, “depressor fibres,” because the effect has been to take off the tonic contraction of the arteries. The same effect is strikingly seen (although it is there accompanied by a conscious mental state) in the rising wattles of a cock, for which class of erectile effects the nerves are called “nervi erigentes.”

But if this kind of turgescence is the best physiological analogy for the redness of inflammation it goes but a little way with us into the morbid condition. The tonic contraction of the arteries is no doubt taken off, and the vessels become distended with blood passing through them; but the next event is peculiar to inflammation,—the current of blood becomes slower, slow even to a stop in some of the numerous cross-channels of the capillaries. There is nothing in the mechanics of the circulation to account for this dallying of the blood at the seat of injury. The further discussion of the subject will be made easier by a reference to slight degrees of inflammation set up experimentally in transparent and delicate parts where the process can be watched through the microscope,— in a piece of frog’s mesentery drawn out through an aperture of the abdomen, or in the everted membrane-like tongue of the same animal. When the microscope was first applied to the study of inflammation these same effects were often observed by Paget and Wharton Jones in the wing of the bat, an animal which has the advantage of being comparatively warm-blooded.

Experimental Study of Inflammation.— The frog having been paralysed by curare, a loop of the intestine is pulled out through a slit in the abdomen, and its mesentery stretched over a ring of cork, so that the light may be reflected to it from the mirror of the microscope. It hardly Avants an irritant, such as a drop of weak acid, to produce the inflammatory effects on this thin membrane; mere exposure to the air suffices. In ten or fifteen minutes the arteries begin to dilate and then the veins, and the vessels go on dilating for the next two hours, when they will have reached about twice their ordinary calibre. They remain so dilated, and in an hour or two the current of the blood becomes slower in them. In the older observations on the bat’s wing acceleration of the current through the dilated vessels was first noted; then came the transition to the peculiar inflammatory action, namely, slowing of the current, the vessels still remaining dilated. This slowing of the stream is most obvious close to the injured point, where there may be complete stagnation in the capillaries, the crowded corpuscles giving the central area a bril1iant carmine appearance. Farther away from this area the streams are more rapid; and at the farthest limits there is the unusually full and rapid flow of normal hyperaemia. The fulness of these dilated vessels exhausts their elasticity, so that the pulse-wave of the blood, which should be felt only in larger vessels, becomes perceptible also in the smallest.

In the area of retardation in the frog the blood-disks and the white corpuscles cling to the sides of the capillaries and small veins, instead of forming, as usual, a procession in the central line of the tube. Most of all do the colourless corpuscles adhere to the Avails, in the experiment on the frog, until they form a kind of outlined mosaic on the side of the vessel. Then, if a particular spot be watched for several hours continuously, it will be found that some of these cells have actually Avorked their way slowly through the wall of the small vein. This is the important phenomenon of emigration of the cells of the blood, known to Gendrin and W. Addison, accurately folloAved by Waller, and rediscovered by Cohnheim.

Incontinence of the Vessel-walls.— The incontinence of the vascular walls in inflammation is proved, not only by this emigration of cells from the small veins, but also by the escape of red blood-disks from the capillaries, and by the familiar and old-established fact of exudation of the fluid part of the blood,—the plasma or serosity. In the words of Alison: “First, the surrounding textures are loaded with a serous fluid; but gradually changes take place in this fluid, which indicate that other constituents of the blood have exuded from the vessels; or part of the fluid effused assumes a gelatinous consistence, and forms flakes or layers which gradually become solid. In the semi-fluid matter first effused, according to Gendrin and others, decolorized globules of the blood may often be perceived; and in many cases globules of pus, known by their larger size and freer motion on one another (and, when observed in mass, by their yellow colour), soon appear in this effused matter; and it assumes more or less rapidly, and more or less generally, the form of purulent matter. . . . Along with the semi-fluid lymph effused in the earlier stage of inflammation there is often extravasation of the colouring matter of the blood, and sometimes of entire blood.” This, then, is the central fact of inflammation,—the incontinence of the vessels and the exudation from them.

Addison adopted the theory that the pus of inflammation was nothing but the colourless cells of the blood that had been washed out with the plasma; and that doctrine has been revived by Cohnheim with little or no reserve. There have been serious objections to this doctrine of the origin of pus; practical surgeons have always failed to understand how all the pus could come from the blood, which has not only a mere trace of colourless cells in it, but, moreover, contains neither more nor less of these cells during suppuration than at other times. Again, in cases of leukaemia, where the number of them is enormously increased, the course of inflammation does not appear to be affected thereby. Lastly, it is pointed out that we cannot infer altogether fully from the extremely susceptible transparent membranes of the frog to the subcutaneous and other connective tissues which are the usual seats of the inflammations met with in practice. So far, then, we are justified in admitting only the incontinence of the vessel-walls, the escape of some colourless cells, and of plasma, the latter yielding fibrin under some circumstances, in combination with the paraglobulin and the ferment known to reside in the white corpuscles.

The cause of the incontinence of the vessel-walls naturally engrosses attention. In an experiment of Cohnheim’s a similar condition was produced in the vessels of the frog’s tongue by ligaturing the tongue bodily at the root, so as to stop the circulation in it altogether. If the ligature were kept on for six days the tongue began to mortify, and the circulation showed no power to re-establish itself; if it were removed after forty-eight hours the current slowly resumed its flow, the arteries returned from their dilated condition, but not the veins, and the colourless cells began to escape from the latter; on removing it after twenty-four hours only, the circulation quickly resumed its normal course without any transient emigration of cells. The conclusion was that the walls of the vessels suffered a certain loss of “integrity” if the circulation through them were stopped beyond a certain limit of time, and this loss of integrity seemed to be analogous to the alteration of the vessel-walls under the blow of an inflammation. On the other hand, it has been pointed out that not the vessel-walls only, but the cells in closest proximity to and in intimate nutritive relation with them, are affected by the stroke of inflammation; avhere such cells have processes, and can be seen, they are found to draw in their processes under an irritant. In the exposition of Cohnheim, however, these changes in the cells of an inflamed part are not admitted to be other than regressive or passive; according to him, the walls of the vessels only are affected, and affected in their molecular constitution.

Suppuration.— We have seen that there still remains the difficulty of accounting for the large quantity of pus; and it will probably be found that to account for the pus we shall have to ascribe a more than passive attitude to the connective-tissue corpuscles of the inflamed area. Where the suppuration is diffuse, as in phlegmon, and still more where it is discontinuous, as in secondarily inflamed lymphatic glands, it is not to be supposed that the pus is a mere aggregate of blood-cells brought thither. Something from the primary seat of inflammation has caused the more distant parts, whether they be continuous or discontinuous, to take on the inflammatory and suppurative action; but it is quite clear, if we examine a lymphatic gland beginning to suppurate, that its own cells yield the pus. There has been an action of presence on the parenchyma of the lymphatic gland; and it will be diíficûlt to account for the production of pus in acute primary inflammation without assuming the same action of presence. In inquiring after the catalytic agent suspicion falls on the substances exuded from the vessels, and mostly upon the emigrated colourless cells. Suppuration, when it occurs, is subsequent to and secondary to the exudation. When no suppuration occurs, as in what is called adhesive inflammation, which is the commonest kind on free surfaces, the exuded blood-plasma simply coagulates, forming a fibrinous layer, in the meshes of which are a larger or smaller number of colourless blood - corpuscles. In the further development these blood-cells are probably themselves the active elements; they produce the tissue of adhesions, which is a form of the tissue of repair. In situations which are not free surfaces—that is to say, in the subcutaneous tissue, or more generally in the tracts or planes of the common binding tissue—the exuded substances are less apt to coagulate or to take the adhesive fibrinous course. It is in these deeper situations that we ordinarily get suppuration, an event subsequent to exudation and undoubtedly dependent thereon. It is true that “inflammation” may be excited on the surface of articular cartilages and in the cornea, where there are no bloodvessels to yield an exudation; but the inflammation is not of the ordinary kind, and in particular there is no true suppuration until the nearest blood-vessels have projected their system as far as, or close up to, the irritated area. Artificial keratitis has been the chosen ground of controversy to determine whether it is the vessels, or not rather the cells, of the part that are primarily and actively concerned in the inflammatory process; but it will probably be found that the two sides of the controversy correspond to two different sets of facts. The transparent superficial ulcer of the cornea has hardly anything to do with inflammation; it does not suppurate, although there is some formative action in the cells of the part to enable it to heal. Whenever there is true inflammation of the cornea it is accompanied by or preceded by extension of the nearest vessels to the transparent and non-vascular surface.

Changes in the Connective Tissue.— In the events of true inflammation, therefore, exudation from the vessels precedes suppuration; and it can hardly be doubted that they are cause and effect, to the extent, at least, that exudation is a necessary antecedent. At the same time the connective-tissue cells of the part can hardly have escaped that molecular injury , v or injury to their nutrition, which the elements of the vascular wall would appear themselves to have suffered; they are, as Rindfleisch points out, intimately bound up with the plasmatic circulation or the ultimate diffusion of the juices; they are in closest relation with the terminal nerve-plexuses; and, histogenetically, they are the remains of that “parablastic” embryonic tissue from which the blood-channels themselves were made. It would be surprising, indeed, if they escaped the shock which had deeply affected the integrity of the cells in the vascular wall. A concurrent alteration, at least, must be postulated for them; but that can hardly account for more than a preparedness in them to form pus. According to Stricker, the elements of the connective tissue revert to an embryonic character before pus is formed from them. If the hardness of the central core of an inflammation under the skin be analysed, it will be found to depend, says Stricker, upon the following things: the tissue is thickened, the network of cells in it is swollen, the intercellular substance is reduced, the network of cells has broken up into independent pieces of nucleated protoplasm. This is the swelling of the tissues which precedes abscess-softening; it is essentially a return to a more protoplasmic and less fibrillar state, and accordingly to a more embryonic state. Of this power of reversion to an embryonic state, which the common binding tissue of the body retains as a memory of development, we have already had illustrations in the processes of repair, of tumour formation, and of cancerous infection. In all these cases the tissue falls back upon a more elementary condition, or we may say that it retreats to broader ground, where, however, it cannot stand still. Its special destiny is settled for it in each case by the circumstances, and, for the particular case of inflammation (as distinguished from the process of repair), its special destiny is to form pus. If the analogy adduced in the section on “repair” has any value, pus is the by-product of a kind of blood-making from the embryonic cells, a haematoblastic activity in which no red disks are formed, but only pus-corpuscles and a fluid, the corpuscles standing for the residual nucleus of the haematoblast (with evidence of cleavage in it) and the liquor puris for both the red disks and the plasma. This haematoblastic doctrine of pus would correspond, in form at least, to Hunter’s conjecture that “the new-formed matter peculiar to suppuration is a remove further from the nature of the blood.” So long as the intensity of the process lasts, the connective tissue uses its reacquired embryonic powers only to make pus; when the effects of the blow have subsided (or if they have been from the first slight, as in the reparative process) the formative powers of the tissue make granulation-cells and new blood-vessels (including even new blood within the vessels), and so the incident ends in repair. The pus of a granulating surface would thus differ from the pus of acute inflammation only in degree. In like manner, common inflammation with a moderate degree of fever differs only in degree from phlegmon, or diffuse suppuration, with its peculiar fever. The diffuse suppuration of phlegmon is the case where the infection or action of presence extends by continuity along the tracts of connective tissue; the implication of lymphatic glands (it may be at the outset) is the case where the infection is carried to a distance by the lymph-drainage of the tissues. Contrasting with such cases, the area of suppuration in a healthy subject (where there has been no extrinsic poison introduced) is a limited one; but, however limited the focus, it seems necessary to resort to infection of the connective tissue for an explanation if the exuded fluid turn to pus or the inflammatory swelling turn to abscess. It is in this sense that every inflammation may be said to be infective.

Assuming, then, that pus-formation is due to an infective influence impressed upon the protoplasmic connective tissue, and knowing, as we do, that the exudation from the blood-vessels is an invariable antecedent, the rôle of infecting cells would precisely suit those elements of the exudation about whose share in the inflammatory process there has been much controversy, namely, the emigrated colourless cells of the blood. As a material contribution to the pus all the cells that escape from the blood would go but a little way; as infecting cells they might be the agents of much suppuration, and, through their wandering propensities, of suppuration at discontinuous points. They would thus have a power in inflammation analogous to that which has been claimed in a former section for catarrhal and other epithelial cells of a mucous membrane (or of a gland) which had found their way into the supporting connective tissue.

Among the things that determine the degree and course of an inflammation, besides the kind and extent of the injury, may be mentioned the florid or anaemic habit of body, the gouty habit, the alcoholic dyscrasia, the diabetic cachexia, the scrofulous inherited constitution, and the syphilitic taint. There are even cases where the predisposing cause is, as it were, strong enough to dispense with all but the slightest exciting cause; where, accordingly, the inflammation λvould be called idiopathic. But, however much the “crasis ’ ’ of the blood or influence of the nerve-force may determine the degree and kind of inflammation, it is clear that the stagnation of the blood, the incontinence of the vessel-walls, the exudation, and the suppuration may all follow an injury where the crasis and the general nervous control are perfectly normal. The significance of micro-organisms in the inflamed area must be judged from the same point of view; all the events of inflammation may happen without them, but they may help to determine the kind and extent of the inflammatory effects.

§ 15.— Infectiveness.

One of the most dreaded results of a wound, or an inflammation from other causes, happily rarer in modern surgical practice than in former times, is pyaemia, septicaemia, or purulent infection. About a week, more or less, after the injury, the patient has a shivering fit followed by a perspiration; he may feel comparatively comfortable for a time, but there soon begin to be grave symptoms of constitutional disturbance. He becomes uneasy, has pains in the limbs, a weak and quick pulse, fever, loss of appetite and thirst, a dry and brown tongue, a somewhat jaundiced skin, and sometimes diarrhoea. The shivering fit returns at intervals followed by the sweating, the temperature rising to a great height and falling rapidly to a corresponding degree. Death usually ensues, sometimes not for two, three, or four weeks, being preceded by muttering delirium and unconsciousness. A curious symptom accompanying these phenomena is the sweetish odour of the breath. Meanwhile the wound, where there is one, will have ceased to discharge pus freely, becoming dry and brownish and yielding only a thin ichor; at a distance from the wound one or more joints may become swollen and painful, or an abscess may form at one or more points under the skin, or there may be pustules and discoloured patches on the skin.

In the examination after death the secondary abscesses may be very various in their seat, oftenest perhaps in the lungs, under certain circumstances in the liver, or in one or more joints, or in the substance of the heart, or at the back of one or both wrists. The parotid glands are peculiarly liable to diffuse secondary inflammation. In a class of cases called septicaemic for distinction, no secondary inflammations or products of inflammation can be discovered anywhere; in these cases the periodical shivering fits are not marked, although there may be profuse sweatings from time to time. In another class of cases, to which Paget has called special attention, the course of the disease is very protracted, being marked by relapses from time to time; and the chances of recovery are found to be in proportion to the chronicity.

In the pathology of these cases attention has always been fixed on the state of the-veins leading from the wounded part, and of the blood in them. The old doctrine was that the veins secreted pus from their walls, which was carried into the blood-stream. This pre-microscopic opinion has given way to the modern doctrine of thrombosis and infective embolisms elaborated by Virchow. Not only the veins leading from an external wound, but the veins of the uterus after delivery, and other internal veins under various circumstances, may become lined by a layer of coagulum, or even blocked in their entire lumen; the coagulum undergoes puriform (although not purulent) degeneration; pieces of it, or molecular particles of it, get washed off, carried into the blood-stream, and lodged as embola in the small vessels of a terminal vascular area of the lungs or other organ or part, where an unhealthy form of inflammation arises secondarily. These events will become more intelligible by reference to a particular case.

A woman undergoes an operation for internal piles—saccular dilatations of the inferior haemorrhoidal veins. The haemorrhoids had been ligatured, and for some reason there ensues an altogether unusual course of events. In a few days the patient has symptoms of pyaemia, and death follows in a fortnight. At the examination the inferior mesenteric vein, all the way up from its ligatured inferior haemorrhoidal branch to where it joins the splenic on its way to the liver, is found much dilated, lying along the left side of the lumbar vertebrae as thick as the little finger, of a greyish appearance externally, and filled with greyish puriform detritus. In the liver, to which this vein conducts, there are a number of inflammatory centres, some of them merely dark-red or livid circular areas, others of them purulent centres or true pyaemic abscesses.

In this case the wall of the ligatured vein had taken on some action which had affected the clot formed naturally within it; instead of the clot organizing, it had become a semi-fluid mass of puriform detritus; it had extended by continuity far up the main trunk of the inferior mesenteric vein, the puriform softening following it; particles or larger pieces of this unnatural clot had passed into the portal vein, and had become impacted in certain capillary territories of the liver, where they had infected the elements of the part (probably the connective tissue exclusively) to take on an inflammatory and suppurative action.

It is questioned by some whether there may not he a class of pyaemic and septicaemic cases in which no thrombosis (with ρuriform softening of the thrombus) of peripheral veins occurs; but it cannot be doubted that this kind of thrombosis, and the discharge of particles or pieces of the thrombus into the general circulation, are very general accompaniments of pyaemia and septicaemia, puerperal and other. The interest centres in the state of the vein-wall, which causes the blood to clot within it, where it would not otherwise have clotted, and causes the clot to undergo a puriform degeneration, or to acquire an infective power. The state of the primary wound must be held answerable in general for all the secondary events, from the thrombosis onwards. In the wound the ordinary products of inflammation cease to be formed, and, instead of them, there is an ichorous foul-smelling discharge, or a dry and semi-gangrenous condition of the parts; whatever this action may be, it communicates itself to the walls of the vessels, and the thrombosis (with detachment of the puriform particles) follows.

There are certain well-understood circumstances in which wounds take on such an action: the crowding of a number of cases of suppurating wounds in a limited space without adequate attention to the removal of the putrid discharges from the wounds, great nervous prostration of the subjects of wounds, the coexistence of kidney-disease, and such-like constitutional states personal to the case. The situation, of the wound or exposed surface comes also into account; thus injuries of the bones (as in compound fractures), and especially injuries of the cranial bones, are more liable to take the pyaemic direction. Above all, the surface of the uterus after delivery, or contused wounds of the labia, or other lacerations, will take on an unhealthy action, either from the circumstances of the patient, or owing to a very minute quantity of infective substance (cadaveric or other) having reached it from without, or from the putrescence of portions of retained placenta. The liabilities of child-bed are increased by the circumstance that the blood in the puerperal condition is unusually liable to clot in the veins, even when their walls are in good condition, and also by the fact that the venous sinuses of the uterus after delivery are such as to afford opportunities for stagnation of the blood in them (unless the vigorous contraction of the organ have practically obliterated them), in which respect they resemble the venous sinuses of the dura mater.

Experimental Septicaemia.— The injection of small quantities of putrid substance into the circulation in animals, such as the dog, produces symptoms of septic poisoning corresponding somewhat to the symptoms as observed in practice. In this experimental septicaemia, as well as in the septic processes of man, there are many facts to show that bacteria are concerned. How these micro-organisms are concerned is another and much more difficult question. According to one view the lowered vitality of the tissues in a certain class of injuries, or in the injuries of a certain class of subjects, gives these ubiquitous organisms their opportunity. In this view the organisms initiate nothing; they are incidental to the morbid state of the tissues, and their presence in large numbers is rather the index of the liability to septic infection than the cause of any septic infection that may occur. The most extreme claim made for these organisms in purulent and septicaemic infection (as well as in erysipelas, ulcerative endocarditis, and diphtheria) is that their physiological activity (if not even their mechanical presence) determines the nature of the morbid process, including the tissuechanges, the type of constitutional disturbance, and, in general, the development, course, and termination of the infection. In judging between the two extreme positions it should be remembered that there -is nothing morphologically distinctive in these organisms found in diseased or injured tissues, that their so-called physiological activity in disease is merely begging the question, and that their mechanical presence, even if they were always present in sufficient numbers, has not yet been brought into any intelligible relation with the symptoms and the morbid anatomy. On the other hand, there cannot be the slightest doubt that one of the greatest desiderata of surgical practice is to keep them out of wounds (see Surgery). Tumour-infection.— This subject has already been treated of in the section on “cancer,” but it will be convenient to add a few remarks on the parallelism between tumour-infection and purulent infection. In both cases we have a primary seat of morbid action and a secondary infection, and in each case the seats of secondary infection correspond on the whole closely. The closest correspondence is perhaps with sarcomatous tumours, which have the same relation to veins that primary infective inflammations have, and the same predilection for the lungs. Again, where the liver becomes the seat of secondary tumours, the first steps of the process of infection are on the whole parallel with those that may be observed in multiple abscesses of that organ, that is to say, the liver-tissues at a number of points undergo changes which are practically simultaneous within a certain radius, leading to a circumscribed abscess in the one case and to a circumscribed tumour-nodule in the other. Both the abscess-area and the tumour-area may be found at half-way stages of their development, the former being often recognizable in the section of a pyaemic liver as a somewhat livid circular spot. In the tumour-process the morphological characters are always very definite, and the exciting agent has plainly come from the primary disease, carrying the structural marks of the primary disease in it. The primary inflammatory process wants the definite structural characters of the primary tumour-process, and still more does it want the endless variety of the latter; but it is still a textural process of the body, and its secondary processes are like it. The tumour-analogy, therefore, is strongly in favour of the idea that purulent infection, and inflammatory infection in general, has an autochthonous origin in the life of the cells and tissues.

Melanosis.— The term “melanosis” is used in pathology in at least two distinct senses. It is applied, in the first place, to the generalization or secondary extension of a primary tumour (usually sarcomatous), containing black or brown pigment; and, in the second place, it has reference to a remarkable generalization or widespread deposition of black pigment in the bone-marrow and elseivhere in the horse, particularly in those horses which are apt to lose whatever hair-pigment they may have had. Each of these two very different cases has its interest for general pathology.

The generalization of a melanotic tumour, even a very small one, is one of the most remarkable facts of infection. It is not unfrequently seen in the case of the spindle-celled sarcomatous tumours which grow from the pigmented connective-tissue cells of the choroid tunic of the eye (not the choroidal epithelium of the retina). In such cases the primary tumour is serious enough from its pressure effects, but it is infinitely more serious from its infectiveness. The liver may be full of large tumour-masses, black throughout or in part, and there may be other secondary growths elsewhere. Even more striking is the generalization which is apt to ensue from a subcutaneous melanotic sarcoma, or from a small spot of pigmented new growth on the basis of an old pigmentary mole, or naevus, or mother-mark (melanotic alveolar sarcoma). The secondary tumours occur at other points under the skin, often widely remote from the primary, and in the axilla, in the membranes of the spinal cord, in the liver, in the lungs, and even on the serous membranes. We have here to do with the ordinary considerations of tumour-infection, as already spoken of; but the presence of pigment in. the cells and partitions of the new growth raises a further consideration. If we collect all the secondary tumours from a case where infection has been extensive, and express from them all the pigment, we should get a very considerable quantity, perhaps half a pint, of a thick black fluid not unlike printers’ ink. The source of all this pigment has been perhaps a small speck of melanotic tumour-tissue in the skin, or, to mention a particular case, in the graqulation-like tumour-tissue in the bed of the thumbnail after an injury. How is it that from so small a source so much of this black substance has been produced?

The pigment is, of course, contained within the individual cells of the secondary tumours; these cells are a mimicry of the primary tumour-elements, and, as they reproduce the form and size of these, so also they reproduce their pigment-granules. So stated, there is nothing remarkable in the quantity of black fluid that may be collected from a case of generalized melanotic sarcoma. The primary tumour impresses the type of its own life upon a number of distant centres of cellular activity, so that these grow to be tumours, their cells at the same time becoming each a laboratory for the manufacture of pigment, extracting it from the blood for their erratic purpose. The true suggestiveness of these events is really in the way of analogy for another class of infections. It is often said that, in an infection like smallpox, the virus must be an independent living organism, because it multiplies within the body during the evolution of the disease, the body which had received a most minute quantity of virus becoming in its turn a centre from which a thousandfold of the virus may issue. But, if a small speck of melanosis may yield half a pint of inky fluid by so impressing the cells of the body that they become so many laboratories of black pigment, then we can understand how, in smallpox, the cells of the skin at many points become laboratories in like manner, not indeed yielding black pigment, but supplying that which has to the primary contagion of a case of smallpox the same relation that the generalized pigment of melanosis has to the primary speck or nodule of pigmented spindle-celled or alveolar sarcoma. It is not necessary a priori to go so far afield as the ferment - action of living organisms for an analogy of this thousandfold multiplication; there is an analogy nearer home in the marvellous metabolic capabilities of the body’s own protoplasm.

Melanosis of the Horse.— It sometimes happens that we find, in the carcase of an aged grey or white horse which had been originally brown or black or other shade of colour, that the marrow of all the ' bones in its body is changed into a uniform black inky pulp or fluid, that the clusters of lymphatic glands are full of the same in a drier form, and that there are black patches on the more exposed parts of the mucous membranes. This remarkable malady is not found except in horses whose coat had lost its originally abundant hair-pigment. Trousseau and Leblanc, who investigated the facts on a large scale at the Paris horse-knackers’, were of opinion that in every horse which had turned white, more particularly if it had been originally black or brown or roan, the inguinal lymphatic glands were full of black pigment; and they concluded that the pigment there deposited was the equivalent of the colouring matter that the hair had lost, and that the blood being, as it were, overcharged with colouring matter, had deposited pigment in unusual j daces.

It is difficult to suppose that the melanosis in these cases is a mere quantitative equivalent of the pigment lost from the hair. The pigment of melanosis is more probably a true metabolic product of cells; and it is significant that it is most abundant, in the horse, in the old seats of haemoglobin-formation, namely, the red bone-marrow. The bone-manrøw (with other tissues as well) takes on a pigment-making activity, coincidently with the blanching of the horse’s coat, and vicariously thereto. The melanosis of the horse is a striking instance of a constitutional malady, that is to say, it illustrates the very important pathological doctrine that an error in one part or function of the organism entails vital consequences elsewhere.

§ 16.— Specific Infections.

Infective disease of one kind or another stands for a very large part of the total sickness and mortality of mankind. It is entitled, therefore, to a larger space in a nosological outline than a single section at the end of an article. Each infective disease has to be considered by itself, from the natural-history point of view, and the salient facts of its history, geography, and ethnology, and its other particular circumstances to be taken along with its morbid anatomy and clinical history. It will be necessary, for the present purpose, to adopt a much more restricted programme, and to indicate little more than the place of the specific infections in the general scheme of disease.

Of diseases that have the property of infectiveness we have already dealt with cancers and other malignant tumours, and with the common infective inflammations. Reference has also been made to erysipelas, which is sometimes not merely infective as regards the individual body in which it arises, but a source of infection (or contagion) also for other bodies through conveyance of a virus. In the communicable class of infections we have to include so ordinary and simple a malady as a common cold, which is notoriously apt to go through a whole household, having been acquired in the usual way by some one member of it. The great historical epidemics of influenza which have overrun whole continents from time to time are held by some to be little else than colossal developments of those catarrhal epidemics which we meet with on a homely scale within single households. Another example of the same kind of communicability of a simple catarrhal affection of a mucous membrane is the Egyptian form of “cold in the eye” or ophthalmia, which was brought to England by a few of the troops returning from the expedition of 1801, and which spread by contagion for several years through the home-garrisons with a virulence quite unknown in the Egyptian climate, so that more than two thousand soldiers had to be pensioned for total blindness due to it.

In such instances a common and, it may be, trivial malady becomes a species of disease; it acquires the remarkable power of reproducing itself in persons who had not been exposed to the primary exciting causes. Not one in a hundred of the soldiers who were blinded by ophthalmia during the first ten years of the century had ever been in Egypt, just as, in a household where catarrh has become prevalent, perhaps not more than one member of it had sat in a draught, or been caught in the rain, or otherwise been subject to the conditions that ordinarily bring on a common cold. It is the acquired catarrhal condition that spreads from person to person, being faithfully reproduced in each new victim. The morbid condition becomes a kind of individual thing, of which the seminal particles are scattered abroad and induce the same morbid condition where they find a favouring soil or a favourable lodgment.

If all the instances of infection could be reduced to the same category as these, we should simply have to regard the specific infective diseases as the spreading or communicable forms of morbid conditions of the body otherwise accounted for—as states of disease leading a kind of independent life, but traceable in the last resort each to its origin in certain structural and functional errors of the body. The great problem of the species of disease would thus become an evolutional problem. While this evolutional problem would always have underlying it the unique difficulty of conceiving how a morbid state of the body could be integrated to become a semi-independent existence, with the power of reproducing itself by its germs as in the generation of living things, the interest for each specific disease would be to follow up, historically, geographically, ethnologically, sociologically, and otherwise, the conditions of body out of which the complex natural history of the disease-species had grown.

Proceeding, then, in the natural-history manner, and attempting, in the first instance, a grouping of the species of disease, the broad lines of division are into the chronic and the acute, and, among the acute themselves, into exogenous and endogenous.

Acute Infective Diseases—Exogenous and Endogenous.— The endogenous species of disease are those in which the infecting particles pass directly from the sick body to the sound, giving rise in the latter to a morbid state which follows the same order of unfolding, and attains the same type as in the former. The exogenous species of disease are those in which the infecting or germinal particles have an intermediate state of ripening in the soil, or in water, or amidst other favouring conditions, producing a definite set of morbid phenomena in the exposed body, but a set of phenomena which may be, and often are, different in important respects from those of the primarily-ailing subject. These contrasts between the endogenous and the exogenous infections may be illustrated by a reference to smallpox on the one hand and to cholera on the other. Any person whose skin is covered with the drying crusts of smallpox pustules may give off infecting particles which will set up the same disease if they find a lodgment in a susceptible person, the contagiousness of such a case of smallpox being somewhat heightened, no doubt, by a close atmosphere and the like. But for cholera, speaking generally, much more than this is wanted for the development of the communicated disease; the infecting particles have in most cases to undergo an intermediate stage of ripening in the soil or in other outside media. Yellow fever is even more than an exogenous infection; it is also vicarious, inasmuch as, over and over again, it has been from the emanations of dysenteric dejecta of the negro (who can hardly take yellow fever), and not necessarily from the effluvia of pre-existing yellow fever cases, that the infective power has proceeded. The vicariousness of yellow fever brings it into close relation with typhus fever, which is not otherwise counted as an infection of the exogenous group. No attempt to trace all cases of typhus to pre-existing cases of the same fever can possibly succeed; the succession has been broken repeatedly, and repeatedly started anew, amidst well-known circumstances of cold, hunger, filth, and general misery. In the larger proportion of typhus cases it is the miserable themselves who have suffered from the disease in addition to their other miseries; but there are numerous classical instances in which the more wretched of mankind have imparted typhus to their more comfortable fellows without themselves exhibiting the symptoms of the disease. The best-known historical cases are the Black Assizes, when prisoners who were brought into court from filthy dungeons so tainted the air of the court-house that the judges, tne members of the bar, the jurymen, and the public were seized with a virulent typhus infection. If, in such cases, it should be contended that the prisoners carried the specific effluvia of typhus about their persons, although they themselves did not suffer with the specific symptoms of the fever, there are other cases where such a contention is entirely inadmissible. Perhaps the most remarkable of these is the case of the Egyptian ship-of-war which brought an epidemic of typhus to Liverpool in 1861. {Epidem. Trans., i. p. 246,1862.) More usually, however, it is the miserable themselves who first develop this morbus miseriae, afterwards communicating it to the physicians and others who enter their dwellings or otherwise come near them. The de novo development of the symptoms of typhus, and subsequently of the independent contagion of typhus, has been abundantly illustrated in the naval and military lιistory down to the close of the Napoleonic wars. The writings of Huxham, Lind, Pringle, D. Monro, Blane, and others, who served in the great typhus period, are full of evidence of that kind; the doctrine of the continuous reproduction of the typhus virus always from pre-existing cases is a purely academical affair, which dates from the ingenious dialectic of Bancroft’s Essay on the Yellow Fever, &c., 1811. The rational doctrine of this kind of infective disease, based upon the practical experience of all times, is that which is stated by Pliny: “Primo, temporis ac loci vitio, et aegri erant et moriebantur; postea, curatio ipsa et contactus aegrorum vulgabat morbos” (xxv. 26).

Relapsing Fever. — Closely related to typhus in the circumstances of its origin is relapsing fever, which has extremely slight power of spreading among the well-to-do. Its synonym of famine fever is on the whole a sufficiently accurate designation of its circumstances of origin. Its more recently-acquired synonym, spirillum fever, is derived from the presence in the blood of a minute spiral living organism, as to which the standing question arises whether it is there because the particular state of fever is favourable to it, or whether the fever is there because the organism has, for some reason, invaded the body. Here, again, the conflict arises between academical dialectic and the more tangible facts of experience. It is maintained that relapsing fever can be given to the monkey by injecting the spirilla; hut that circumstance by no means serves to show that the pre-existing cases of relapsing fever had occurred because spirilla had invaded the bodies of a certain number of persons. Relapsing fever is sometimes, though rarely, conveyed by infection to those who had not been living in a state of overcrowding and of semi-starvation; and such an incidence of the disease is so entirely arbitrary that even the spirilla, if they came from other cases, might be accepted as the active agents. The spirilla would have a real interest if it could be shown that they could initiate relapsing fever proprio motu. As the case stands, the predisposing causes of relapsing fever completely overshadow all other elements in the causation. The disease is always and everywhere morbus pauperum, and very often it is typhus famelicus. Typhoid fever.— This fever holds a peculiar place in the history of specific diseases. It is unquestionably a far more common disease at present than it was fifty years ago, and it is certain that it was prevalent in Paris for some time before it began to occur, except as a rarity, in London and Edinburgh. The evidence of Christison and of other highly observant pathologists may be implicitly accepted that, while Louis and others in Paris were finding ulceration of the small intestine in fatal cases of typhus-like fever, no such lesion was ordinarily found in the Edinburgh practice. More generally, it may be said that typhoid fever has been a prominent factor in the mortality during the periods when typhus has been an insignificant one. The coincidence of decided typhoid years with the cholera years is perhaps irrelevant. But there can be little doubt that there is a close connexion between the rise of typhoid and the more or less considerable diminution of intermittent fever; there is indeed much evidence in a certain number of localities in favour of the opinion of Boudin, that malarial fever and typhoid fever are mutually exclusive in a given place.

Typhoid fever is undoubtedly a disease associated with the manner of disposal of human excrement. Whether the typho-malarial fever of the American Civil War, and of Rome, Naples, and other localities, is also an excrementitious infection is not so clear. The ordinary typhoid is peculiarly bound up with the modern system of water-closets and sewers, and with the faulty construction of the same; it was a familiar observation in Edinburgh that the Old Town, with its closes and huge tenement-houses, without the water-closet system, remained practically free from typhoid for many years after the disease began to be common in the New Town. The association with faulty sewerage js, however, not an invariable one. The disease occurs among remote and primitive communities, such as Norfolk Island in the Pacific, in Fiji, in Greenland, and elsewhere.

According to the contention of Murchison, and of many other living authorities, typhoid fever may, and often does, develop cte novo in an individual who has received, either by the breath or in his food or drink, some peculiar or not altogether ordinary product of faecal decomposition. It is not alleged by this school that faecal decomposition under ordinary circumstances (especially under the free access of air) is attended with the risk of typhoid fever; but that a virulent property may, and often does, develop under some peculiar concurrence of circumstances, especially when faecal matters percolate and accumulate where little air reaches. If the process of typhoid fever be so induced in an isolated case, the dejecta of the patient are specifically virulent; and from one such case many may be poisoned by means of specifically tainted water or milk distributed in common. The possibility of a de novo origin of typhoid fever now and then is vehemently objected to by the more doctrinaire school of pathologists; according to them there is always a pre-existing case, the virus of typhoid having been continuously reproduced ah aeterno. The Exanthemata.— Another class of acute infections is those which are virtually independent of external circumstances, which affect all classes equally, and which pass by direct contact from the sick to the sound. The chief diseases of this class are smallpox, measles, and scarlet fever. As to smallpox, it has been contended, on the historical and geographical evidence, that it is primarily an African and Indian skin-disease which has acquired spreading power; and there is really no rival hypothesis of its origin. For measles the evolutional clue would appear to be entirely lost. The old notion about it, expressed in the name “morbilli,” was that it corresponded to a lesser kind of smallpox. There can be no doubt, however, of its present absolute nosological distinctness. It is as universal in its distribution as smallpox, sparing no race, and, like smallpox, committing its greatest ravages among virgin communities and among the dark-skinned. The natural history of scarlet fever is altogether different. It is peculiarly a disease of northern Europe; it is practically unknown as an epidemic throughout the whole continent of Asia (except Asia Minor), and the whole of Africa (except Algiers); and in North and South America and Australasia it seems to have followed the European immigration. One of the most remarkable facts concerning it is that it may occur in quite sporadic or isolated cases in extra-European countries. Some favourable concurrence of circumstances had given it a permanent hold in Europe, or had enabled an occasional erythema of the skin, with fever, to develop into a species of disease, in which the almost diphtheritic affection of the throat, the brawny swelling of the neck (with tendency to sloughing), and the acute affection of the kidneys may be so pronounced in certain individuals, and in all the cases of certain epidemics, or of the epidemics of certain localities, that the simple type of disease is obscured and the line of evolution lost. Perhaps one clue to the development of scarlatina from non-specific states of the body may be found in the cases of scarlet rash in children, in the surgical wards of hospitals. The evidence seems to show that in such eases there is something different from a merely heightened predisposition to the specific scarlatinal poison, on the supposition that the latter is ubiquitous; that there is, in fact, an inherent liability in some children to develop a scarlet rash, with fever, near a wound or sore, the condition so developed becoming communicable to others, as in the analogous case of erysipelas.

Chronic Infective Diseases. — The greatest of the chronic infections is syphilis, unless, indeed, we admit tubercle unreservedly into the same class. Its enormous prevalence in modern times dates, without doubt, from the European libertinism of the latter part of the 15th century. It is almost certain that the same disease, with symptoms of constitutional infection, had developed in various parts of the ancient world under similar circumstances; but it is not less certain that a great redevelopment came in about the year 1490 in France, Italy, and Spain, so that we do not even require to assume a continuity of the virus from earlier times. The historical evidence may be read, in a convenient abridgment, in the third volume of Häser’s Geschichte der Medicin und der epidemischen Krankheiten.

Two forms of sore are described concurrently in all writings upon syphilis, and, although it has been usual during the last thirty years to regard only one of these as truly syphilitic, there has always been a certain inability in the profession at large to apprehend the reason for making a radical distinction. One of the forms is a considérable and quickly-developed ulceration, sometimes multiple and with a marked tendency to extend its borders; it heals under treatment, like any other ulcer, and in many cases there are no after-effects throughout the body generally. The same person may develop such sores repeatedly. For a considerable time after the establishment of the doctrine of “true” or indurated infecting sore it was taught that these simple ulcers were never followed by constitutional infection; but it is now very generally admitted that such teaching is too rigid or dogmatic, not according with the facts of experience. A recent writer on the subject in Berlin, who has kept records of his private practice, estimates that no fewer than 40 per cent, of all the cases which developed constitutional symptoms were consequent on primary ulcerations that would not have been included in the definition of “true” or Hunterian sores. It is not seriously disputed that these simpler ulcerations may arise independently of conveyance, as the direct results of gross personal negligence. It is at the same time admitted that they may become inveterate, that the process of healing may become irregular, and that they may gradually acquire that character of “induration” which is distinctive of the “true” sore. The various circumstances under which this change of type or development of characters may take place have, for obvious reasons, escaped being recorded with scientific accuracy; but of the fact of some such evolution there can be hardly any doubt.

The “true” or Hunterian sore is usually at first a small indurated papule, which breaks after a time, but causes little trouble in healing. The after-effects are, in their severity and long-continuance, in striking contrast to the disease at the outset. This form of the disease is an affair of infection from beginning to end, from the primary papule to the “gummatous” internal nodules years after; there is no evolution in the individual of an infective virus out of a common and unclean ulceration. The simple sore, the result of common inflammation under circumstances of gross personal negligence is not without a degree of infectiveness of its own. It has a tendency to spread, to enlarge its borders by including the margin of sound tissue in the ulcerative process, and it has also a tendency to infect the nearest packet of lymphatic glands with a suppurative action. Further, it is highly communicable to the persons of others by contact, reproducing one or more sores very like itself, and such communication is accountable for its wide distribution. But that degree of infectiveness is a very different thing from the true and full syphilitic infection. The latter is often an affair of years, and, it may be, of a lifetime, and it passes directly to the offspring. Its earlier constitutional manifestations are in the throat, the skin, and the hair; its later in the bones, some muscular structures and some of the viscera, and more particularly in their blood-vessels, or in the blood-vessels of their coverings. It infects the lymphatic glands with an indurative rather than a suppurative process, and not only the nearest packet of them but also the lymph-glands in the neck and elsewhere.

In seeking for the beginnings of this profound constitutional taint, for the first steps in the evolution of the infection out of a common morbid state of the body, we naturally arrive at that irregular process of healing, or the inveterate soreness which the granulations of a simple ulcer (due to personal uncleanness or contact with the same) sometimes assume. The tissue of syphilitic formations, wheresoever occurring, has been named by Virchow “granuloma,” being a persistent state of granulation - like tissue, not proceeding to ordinary cicatrization, but to indurative and degenerative clianges. In true syphili¾ as we have said, this kind of formation is from first to last the product of an infective virus, equally the primary hard papule, the indurated lymph-glands, the thickening and destruction of mucous surfaces, the nodes and inflammatory products in the periosteum, and the gummata in and upon the viscera. But the type of all this mimetic formative action must have been somewhere acquired or evolved; and we shall probably not err if we seek for the acquisition of the granulomatous type in the inveteracy and irregular healing of the granulations of an ordinary foul sore under the peculiar circumstances of its own degree of local infectiveness, and in the continuous reproduction of such sores. In this way we should have granulations becoming specifically infective towards the body, or its distant parts, just as the products of simple acute inflammation may be infective to a distance, or as melanotic and other slight primary tumours are apt to propagate their texture and characters far and wide, or even as a common granulating sore under certain circumstances of irritation may develop the characters of tumour-tissue and a high degree of tumour-infectiveness. The products of syphilis have a near affinity to new growths of the tumour kind; and it is with justice that Virchow includes them among tumours as one of the granulomata, and Klebs makes provision for them, along with tubercle, glanders, lupus, &c., in a class of “infective tumours.” If we take the primary type to be the granulation-tissue of repair we shall assign it an intermediate position, and, at the same time, do justice to the circumstances in which this infective granulation-like new growth probably bad its origin, namely, the reparative process in inveterate or neglected ulcers of common and every-day origin, but with a contagiousness of their own, and with a certain infectiveness of their own towards the adjoining tissues and the nearest packet of lymphatic glands.

The most characteristic form of the generalized syphilitic infection, which may not manifest itself for several years after the reception of the virus, is a nodular or infiltrating new growth in various organs—in the liver, in the testes, in or upon the brain, in the muscles (tongue and jaw-muscles especially), in the periosteum, and in the lungs. These nodules are called gummata from the somewhat tenacious, firm, opaque brownish appearance of the fresh-cut surface. The structure, where its vascularity is perfect, consists of small round cells lying mostly in rows among thin fibres, and it closely resembles granulation - tissue, only that the cells are smaller and the intercellular substance (fibres) harder or denser. Molecular death, or necrosis, overtakes this new formation at various central points, owing to the inadequacy or suppression of the blood-supply. One of the most remarkable features of the process is the enormous overgrowth of cells in the inner coat of the arteries within the affected area, leading to an accumulation of elongated cells and intercellular substance, which may even obliterate the channel of the vessel altogether.

Over the later products of syphilitic infection, both the nodular and the infiltrated, there are two drugs, mercury and iodide of potassium, which have a remarkable power, causing their absorption and conducting the infective process to a safe issue. Syphilis has been compared by Hutchinson to a very prolonged fever, with its stages separated by intervals of months; like a fever, it burns itself out, so that a time comes in the course of years, if the patient have not succumbed to the effects, when the system is practically free of the virus, just as it is free of the virus of smallpox in three weeks. In a certain proportion of cases only the secondary symptoms occur, and not the tertiary, the virus having presumably exhausted itself in the earlier manifestations.

In the syphilis of the offspring it is necessary to distinguish two classes of effects. On the one hand, there are the effects of general intra-uterine mal-nutrition, due to the placental syphilis of the mother; and, on the other hand, there are the true specific effects acquired by inheritance from either parent and conveyed, along with all other inherited qualities and tendencies, in the sperm-elements or in the ovum. These two classes of effects are commingled in such a way as not to be readily distinguished; but it is probable that the erroneous growth of bone, at the epiphysial line in the long bones (sometimes amounting to suppuration), and on the surfaces of the membrane-bones of the skull, is a result of general placental mal-nutrition, like the corresponding errors of growth in rickets. The rashes and fissures of the skin, the snuffles, and such-like well-known symptoms in the offspring of syphilitic parents are to be counted among the true mimetic effects of the specific taint; so also the peculiar nuclear overgrowth in the supporting tissue of the liver, the interstitial pneumonia alba of the lungs, and the like. As in rickets, it is in many cases some months after birth before the congenital syphilitic effects show themselves, while other effects, such as interstitial keratitis, the mal-formations of the permanent teeth, and the rarer occurrence of laryngitis, come to light during childhood and youth. Injury to a syphilitic child is apt to have unusual consequences; thus a blow on the arm may be followed by a gummatous growth in one of the muscles.

Tubercle and Scrofula.— Tubercle and scrofula are among the commonest and most fatal diseases of mankind. No chapter in pathology has a more pressing interest; none is surrounded by so much theoretical difficulty, or concluded by so much practical failure. It is not only in Europe, but in America and the British colonies, as well as throughout the whole inter-tropical zone, that this remarkable wasting disease is found. The most considerable degree of immunity is said to be in Iceland and on the Asiatic steppes. While the mortality from this disease is very great, in some European countries amounting to one-seventh of the deathrate, and that, too, among the youth and flower of the people, there is everywhere evidence that a very much larger proportion had incurred a slight degree of the malady and had survived it. Nothing is more common in the course of post-mortem examinations than to find traces of “obsolete tubercle λ in the lungs and lymphatic glands. Cohnheim recalls with some approval a saying that used to be current at Greifswald, that almost eveιy one proved to have been “a little bit tuberculous”; and Rindfleisch bases his pathology of the disease on the assumption that a tuberculous disposition has become practically universal throughout the human stock, so that inflammations, under certain aggravated circumstances, may light up the disease in almost any one. It is peculiarly common in prisons, barracks, and workhouses; and, in the last-mentioned, tubercle and scrofula are not rare among the aged. There are instances within the knowledge of most people where the marriage of first cousins, and still more certainly of double cousins, has been followed by a very pronounced consumptive tendency in the offspring, even if there had been no very clear history of consumption on either side before. No disease runs more in families than tubercle. While there are all these evidences of a widespread constitutional liability to tubercle, it is at the same time clear that the victims of the hereditary taint are only here and there,—perhaps one out of a large family, or one member of a family in childhood and another in the second half of life, according as they had been exposed to sufficient exciting causes. In the most extreme cases of heredity, which are not so rare but that one or more are familiar to every circle, the members of a family fall into consumption one after another as they grow up, as if by an inevitable fate.

The relation of scrofula to tubercle is a subject of much intricacy. The familiar instances of scrofula are the enlarged clusters of lymphatic glands of the neck in boys and girls, who are either of the fair and delicate type or of the dark ana coarse type. Another large class of scrofulous cases are subject to white swellings or other chronic diseases of joints, usually the knee, hip, or elbow. But many slighter conditions, such as eczema of the head and face in children, are set down to scrofula. Again, serious visceral disease leading to a fatal result, especially in the kidneys, testes, ovaries, and bladder, is for some reason reckoned scrofulous rather than tubercular. But this latter class of cases is certainly tubercular, as much as anything can be said to be tubercular. A great part of all that is reckoned scrofulous may be said to be inherited tubercle, affecting the lymphatic glands of the neck most conspicuously, running a very chronic course, often disappearing at puberty, and associated with a delicate skin, fair hair, large eyes, and other features of a well-known type. Of the cases of scrofulous disease in the genito-urinary system and in the joints there may be some in which the disease had been inherited, but there are others in which it had been acquired. The senile scrofula of workhouses and the like is almost certainly an acquired condition. Whether as an inherited disease or as an acquired, scrofula can be separated from tubercle by no very definite line.

Tubercle, as the name implies, is a small tuber or round nodule; the nodules are often “miliary” or the size of millet-seed. For the variety of diffuse or “infiltrated” tubercle, which is often found in the lungs, it has been made a question whether it should be reckoned as tubercle at all, by reason of its wanting from first to last the character of distinct small nodules. Tubercles are sometimes large, especially the tubercles of the genito-urinary organs and of the brain; and these are generally made up of a number of smaller nodules fused together, and surrounded by a common capsule. The larger tubercular masses, or conglomerates of tubercles, are those that have been claimed as in a peculiar sense scrofulous. The fusion of numerous small tubercular centres into one large area can often be seen in lymphatic glands in all its stages under the microscope. The prevalent modern opinion is that all these various manifestations are due to the infective action of a virus, just as in syphilis; and, as the effects of the syphilitic virus include not only gummatous nodules but also “inflammations ”of the skin, mucous membranes, periosteum, and other textures, so the effects of the tubercular virus include not only “tubercles,” properly so called, but also a variety of diffuse “inflammatory” conditions.

The most common seat of the tuberculous process is the lungs, so that tubercle and phthisis pulmonalis have almost come to be synonymous. In a certain proportion of cases the tubercles and tuberculous “infiltrations” are found in the lungs only; but in many cases the pulmonary tuberculosis is only a part of a general infection which includes the serous membranes and lymphatic glands, the intestine, the liver, the spleen, the kidneys, the brain-membranes, the choroid coat of the eye, the bones, and the joints. Cases have been described also of tuberculous ulcers of the tongue and stomach, and of tubercles in and around the thoracic duct. On the assumption that tubercle is due to an introduced virus, it has been attempted to classify the cases according to the probable way of ingress of the virus; those with the pulmonary condition most prominent would have received the infection with the breath, while another class, including the numerous cases where miliary tubercles are found in the liver when carefully looked for with the microscope, would have absorbed the virus along with the food from one part or another of the digestive mucous membrane; the tuberculous kidney (with uretere and bladder), again, would be explained on the hypothesis of that organ attempting to eliminate the virus from the system. But even among the pulmonary cases there are some in which the tubercles had arisen from infection brought by the venous blood, just as in the dissemination of sarcomatous tumours; it has been shown by the very elaborate dissections of Weigert that tubercles may grow into the walls of veins, the tuberculous substance so getting carried into the blood-current, wherein the first resting-place would be the pulmonary capillaries, except when the vein was tributary to the portal system.

It is difficult to say what is the most characteristic structure of a tubercle. In the class of small grey translucent tubercles, all the same (miliary) size, the cells are practically granulation-cells; these are not uncommon in childhood and youth, where the attack is sudden and the progress rapid. In another kind, which Rindfleisch would regard as distinctively “scrofulous,” the substance is opaque and yellowish-white; there are many epithelial-like cells, or cells with a considerable zone of protoplasm round the nucleus, and, mixed with these, giant-cells or cells with many nuclei, usually marginal. Except in the most acute cases of miliary tuberculosis, the new formation, whether in the shape of isolated nodules or continuous tracts of “infiltration,” undergoes changes. Sometimes it becomes a fibrous substance, but by far the most common change is into a yellow cheesy matter. This degeneration is comparable to the gummatous change in syphilitic formations, but in tubercle the degenerate tissue is much less cohesive, more friable, drier, more apt to fall into a molecular detritus. The caseous change is the distinctive degeneration of tubercle, the more occasional fibrous and calcareous changes being either its associates or its modifications. The reason of this change is the insufficient blood-supply of the new formation. Nothing so clearly accounts for the structural as well as the degenerative characters of tubercle as growth of tissue without adequate provision for admitting the blood into it Bovine Tubercle.— In the corresponding disease of the domesticated bovines—a very common disease of cows in town dairies—the characters of the new formations are equally determined by the kind and degree of blood-supply. In this form of tubercle the nodules are, in the first instance, on the serous membranes of the thorax and abdomen; they often attain a considerable size, and sometimes the size of quite large tumours; the vascularity of their surface is very considerable, and it is around their periphery that they grow, as in the case of sarcomatous tumours; but the· blood-vessels do not go all through the nodules, their central parts being either calcareous, or caseous, or reduced to a thick lúortar-like substance. The chief differences between this form of tubercle and the varieties ordinarily met with in man are that it is a more vascular structure, more like a sarcomatous or fibromatous tumour, with a power of growth from its surface (where the vessels are numerous), and sometimes attaining a great size, often suspended from the serous membrane by a vascular stalk or pedicle, and, in the interior of organs such as the lung, surrounded by a translucent capsule of vascular tissue, or excavated into a smooth-walled cavity, the thick translucent capsule being all that remains of the original nodule.

The origin of these peculiar multiple new formations in the domesticated bovines is a more likely subject of inquiry than the origin of human tubercle. The bovine disease is generally admitted to have its nodules referable to two distinct classes—primary and secondary: the primary are the multiple nodular tumour-like growths of the serous membranes, and the secondary are the infective descendants of these in the lymphatic glands, the lungs, the liver, spleen, kidneys, Fallopian tubes, bones, and joints. The secondary infectiveness of primary new growths is otherwise intelligible, according to analogies, and the interest therefore centres in the conditions of origin of the primary, parent, or infecting growths on the serous membranes. They occur by far most frequently in the cows of town dairies, that is to say, in animals closely confined for long periods, deprived of pure air and sunlight, forced in their feeding and milking, and altogether placed under such conditions of nutrition as commend themselves, not to an intelligent acquaintance with ruminant requirements, but to the short-sighted maxims of profit and loss which govern the policy of the cowkeeper. The vicissitudes of nutrition are pretty clearly indicated as the starting-point of tubercle in the cow.

In human tubercle we have no such indications of a division into primary new formations arising out of errors or vicissitudes of nutrition in some tissue, and into secondary new formations due to the infectiveness of the primary. On the other hand, the various new formations in a case of tubercle in man would appear to be co-ordinate, or all of them due to a common cause. Human tubercle is not by any means a multiple nodular eruption on the serous membranes first and in the lymphatic glands and lungs afterwards; if the disease occur in these three localities it is necessary to assume the same infective cause for it in them all. Most usually the first indications of human tubercle are at the apex of one or both lungs, and, in a considerable proportion of cases, the disease never goes beyond the lungs. But it is not on that account a purely pulmonary disease. For some reason the lungs are most apt to become the seat of the. infection; but there are many cases in which the infection locates itself elsewhere as well, and there are some cases in which it avoids the lungs altogether. An infective virus has to be assumed, and yet we are unable, as in bovine tubercle, to discover any primary source of it in the physiological aberrations of the human body itself. The problem of human tubercle, therefore, may be said to be: Does the infection reach the body from without? and, if so, whence are its structural or morphologically mimetic characters originally derived? While some such question as that has to be stated for human tubercle in the last resort, it has to be kept in mind that a very large part of the sum-total of human tuberculous disease is an affair of strong hereditary predisposition, and even of direct inheritance. In bovine tubercle itself, which is often acquired de novo by cows subjected to grossly artificial conditions of life, inheritance is credibly estimated to be answerable for more than one-half of its present very considerable total.

The pathology of tubercle (bovine and other) has had much light thrown on it by experiments to produce it artificially in animals by inoculation of minute quantities of tuberculous matter under the skin, or by mixing considerable quantities of tuberculous matter with the food for a length of time, or by feeding with the milk of tuberculous cows. A very suggestive proportion of all such experiments have succeeded. It has been boldly alleged by Koch that the active agent in the inoculative production of tubercle is not the tuberculous matter from a previous case, but a minute rod-like living parasite belonging to the order of schizomycetes (see Schizomycetes). According to this view tubercle is from first to last an affair of a parasite, equally the human tubercle and the bovine, although these two forms of tubercular diseas*e are widely different in their anatomy. The weak point in the experimental evidence of Koch is that we are not sufficiently assured of the absolute separation of the ’ tuberculous matter from the parasites. There is not reason enough to suppose, from the published details of these experiments, that the original tuberculous matter had all been got rid of; and there is therefore not reason enough to suppose that the induced tuberculous infection is due to anything but that matter itself, whose infective power, although not initiated by the organisms present, would probably be multiplied by their cultivation.

In the same class with syphilis and tubercle should be taken glanders, primarily a disease of the horse, but now and then communicated to man. There are various tropical and sub-tropical granulomatous infections of great scientific interest which can only be mentioned, such as yaws, vemιga Peruviana, Aleppo boil, Delhi boil. There is also the button-scurvy of Ireland, now probably extinct. Lupus holds a peculiar place in this class of diseases. The position of leprosy also is an intermediate one, and its pathology the most difficult of all the constitutional endemic infective diseases. It was with reference to leprosy, and with particular reference to its enormous mediaeval prevalence and subsequent extinction in most parts of Europe, that Sir James Y. Simpson wrote as follows in 1841 (“Antiquarian Notices of Leprosy and Leper Hospitals in Scotland and England,” Edin. Med. and Surg. Joιιrn., vol. Ivi. ) :—“ ‘ The generatio de novo of a really new species of disease,’ says Dr Mason Good (Study of Med., L pref. p. xxιit), ‘is perhaps as much a phenomenon as a really new species of plant or of animal. ’ Dr Good’s remark is probably too sweeping in its principle; for, if necessary, it might be easy to show that, if the particular diseases of particular animal species are liable to alteration at all, they must necessarily alter more frequently than those animal species themselves. In pursuing such an inquiry the pathologist labours under comparative disadvantages. The physiologist can, by the aid of geological research, prove that the individual species of plants and animals inhabiting this and other regions of the earth have again and again been changed. The pathologist has no such demonstrative data to show that, in the course of time, the forms and species of morbid action have undergone great mutations, like the forms and species of normal life. But still we have strong grounds for believing that, in regard to our own individual species alone, the diseases to which mankind are subject have already undergone, in some respects, marked changes within the historic era of medicine.”

§ 17.—Toxic Diseases.

In various parts of the world and at various periods there have been widespread outbreaks of sickness due to certain toxic or poisonous substances mixed with the staple food of the people. Perhaps the best known of these is gangrene caused by ergot of rye. One form of the disease is characterized by acute pain and gangrenous destruction of the skin, the gangrene sometimes spreading to the deeper structures and to the bones, and leading to loss of the limbs. At times the mortality from this disease has been great. Numerous epidemics of it have occurred in France (rarely during the present century); in other parts of the continent of Europe (Sweden, Norway, Russia) the effects of ergotism have taken the form of a nervous (convulsive) disease called “Kriebelkrankheit.” The effects are those due to ergot, the compact mycelium of Claviceps purpurea, produced within the paleae of the common rye. This substance, well known in medicine, is accidentally ground with the rye, and produces gangrene by contracting the muscular coats of the arteries of the skin so as to seriously diminish the amount of blood sent to it, or it affects the nervous system. (See Ergot.)

Another toxic effect closely allied to ergotism is the pellagra of Lombardy. (See Pellagra.)

A third disease of the same kind is aerοdynia, having a resemblance to ergotism on the one hand and to pellagra on the other. It appears to be somehow connected with bad grain, but the actual poison has not been traced, as in the case of ergot. The observations relating to it have been mostly made in France, and in the French army in Syria, in Algiers, and in Mexico. The succession of symptoms is somewhat complex, including disorders of the stomach and intestine, conjunctivitis, oedema of the face, disorders of sensibility and locomotion, and erythematous rashes, mostly on the hands and feet.

In Colombia (South America) a peculiar disease, characterized by the hair coming out {pelade'), is traced to the ergot - parasite of maize.

In the prairie States of the American Union there is a disease of cattle (and sheep) called “the lremblesT supposed to be due to some toxic substance in the pasturage. In the human subject in those localities there is a corresponding malady called “the milk-sickness" and suspected of being caused by partaking of the milk or flesh of cows which had been primarily affected.

Among toxic diseases we have to include also lead colic, or “dry belly-ache,” to which workers in the various compounds of lead are liable, as well as communities here and there whose food or drink, in the course of its preparation or storage, has been contaminated by lead. Workers with phosphorus, also, are liable to necrosis of the lower jaw. More occasional effects are produced by some other chemical elements used in manufacture.

By far the most important toxic agent is alcohol, which is often sold in public - houses when it has all the powerfully injurious properties of new spirit in it. The enormous excise duty of 10s. per gallon is apt to make us forget the coarse and cheap nature of the alcohol often sold as whisky; this product of distillation may be purchased new from distilleries at as low a rate as Is. 6d. per gallon. The retailing of such new whisky is answerable for an amount of disease—to say nothing of violence and crime —which an equal quantity of mellowed spirit would by no means produce. There are some not uncommon forms of kidney-disease and of liver-disease which are, in the great majority of cases, the direct results of raw spirits. Both in the liver and the kidney the effect of such spirits is to cause an active growth of the supporting tissue of the organ at the expense of its proper metabolic or glandular tissue. In the case of the liver it causes cirrhosis or hobnailed liver, which is accompanied by abdominal dropsy; in the case of the kidney it causes a contracted condition, to which the name of cirrhosis is also applied, being one of the forms of Bright’s disease. Besides these organs the stomach is apt to become affected by coarse spirits taken frequently; it falls into a state of chronic catarrh, on the basis of which cancer is apt to plant itself.

§ 18.— Parasitic Diseases.

Reference has been made to the occurrence of a spiral micro-organism in the blood in cases of relapsing fever, to the so-called “bacillus of tubercle,” and to the occurrence of micrococci in erysipelas and infective inflammations. For the splenic fever and other anthraceous diseases of the domestic animals, very conclusive experimental evidence has been brought forward by Pasteur and others that the virus somehow goes with or resides in the bacilli which are apt to swarm in the blood. These bacilli also occur in the malignant pustule and wool-sorters’ disease of man,—forms of anthrax which are produced by handling the hides and fleeces of animals. In diphtheria and ulcerative endocarditis micrococci are abundant in the tissues of the affected localities. They are also described for malignant osteomyelitis, and a peculiar double form {diρlococcus) has been discovered in pneumonia. The doctrine of infective parasitism is applied by some pathologists to the whole of the specific infective diseases, acute and chronic, as well as to malarial fevers, which are non-communicable. There can be no doubt of the occurrence of very various forms of micro-organisms in the tissues after death from diseases, specific and other, and in the blood and tissues during the course of some diseases, and even in states of fair health. It is premature to call all these bacteria “pathogenic.” Their significance in morbid states of the body will be considered, along with their natural history, in the article SCHIZOMYCETES.

The animal parasites infesting the human body and the fungi concerned in some skin-diseases and in actinomycosis are treated of in the articles Parasitism, Nematoγdea, and Tapeworm. (c. c.) Index. [table] [table] [table] [table]