Bible Encyclopedias
Pathology

Classification

From the foregoing it will be gathered that the problems in pathology are many-sided and require to be attacked from all points of vantage; and the subject falls naturally into certain great divisions, the chief of which are the following: I. Morbid anatomy.

(a) Naked-eye or macroscopic.

(b) Morbid histology or microscopic.

II. Pathological physiology.

III. Pathogenesis.

IV. Aetiology.

V. Pathological chemistry.

The term " pathogenesis " has reference to the generation and development of disease, and that of " aetiology," in its present bearing, has to do with its causes. The use of the term " pathological physiology " may at first appear strange, for if we define physiology as the sum of the normal functions of the body or organism, it may be hard to see how there can be a physiology which is pathological. The difficulty, however, is more apparent than real, and in this sense, that if we start with a diseased organ as our subject of inquiry, we can quite properly, and without committing a solecism, treat of the functions of that organ in terms of its diseased state.

Influences Working For Evil Upon The Organism (I) Malnutrition. - When the blood supply is entirely cut off from a tissue the tissue dies, and in the act of dying, or afterwards, it suffers certain alterations dependent upon its surroundings. Thus, when the circulation to an external part is obstructed completely, as in the case of a limb where the main artery has been occluded and where the anastomatic communi cations have not sufficed to continue the supply of blood, the part becomes gangrenous (fig. 24, Pl. II.); that is to say, it dies and falls a prey to the organisms which excite putrefaction, just as would happen to any other dead animal tissue were it unconnected with the body. Fermentative changes are set up in it, characterized by the evolution of gas and the formation of products of suboxidation, some of which, being volatile, account for the characteristic odour. In the formation of these the tissues break down, and in course of time lose their characteristic histological features. The blood suffers first; its pigment is dissolved out and soaks into the surroundings, imparting to them the pink hue so diagnostic of commencing gangrene. Muscle and white fibrous tissue follow next in order, while elastic tissue and bone are the last to show signs of disintegration. The oil separates from the fat-cells and is found lying free, while the sulphuretted hydrogen evolved as one of the products of putrefaction reacts upon the iron of the blood and throws down a precipitate of sulphide of iron, which in course of time imparts to the limb a range of colour commencing in green and terminating in black.

The temperature at which the limb is kept, no doubt, favours and hastens the natural process of destruction, so that putrefaction shows itself sooner than would be the case with a dead tissue removed from the body and kept at a lower temperature. Nevertheless, gangrene is nothing more or less than the putrefactive fermentation of an animal tissue still attached to the body. If the amount of liquid contained in the tissue be small in quantity the part mummifies, giving rise to what is known as " dry gangrene." If the dead part be protected from the ingress of putrefactive organisms, however, it separates from that which is living without the ordinary evidences of gangrene, and is then known as an " aseptic slough." Should the portion of tissue deprived of its circulation be contained in an internal organ, as is so often the case where the obstruction in the artery is due to embolism, it becomes converted into what is known as an " infarction." These infarcts are most common in organs provided with a terminal circulation, such as prevails in the kidney and spleen. The terminal branches of the arteries supplying these organs are usually described as not anastomosing but many, if not all, of Cohnheim's end-arteries have minute collateral channels; which, however, are usually insufficient to completely compensate for the blocking that may occur in these arteries, therefore, when one of them is obstructed, the area irrigated by it dies from malnutrition. Being protected from the ravages of the organisms which induce putrefaction, however, it does not become gangrenous; it is only where the obstructing agent contains these organisms that a gangrenous slough follows, or, in the case of the contaminating organisms being of a suppurative variety, ends in the formation of a so-called " pyaemic abscess," followed by rapid dissolution of the dead tissue (fig. 24, Pl. II.). In ordinary circumstances, where the artery is obstructed by an agent free from such organismal contamination, the part becomes first red. This is due to intense engorgement of the vessels brought about through these minute existing collateral channels and results in a peripheral congested zone round the infarct. There may be haemorrhage from these vessels into the tissues. This collateral supply not being sufficient to keep up the proper flow of blood through the part the veins tend to become thrombosed, thus increasing the engorgement. The central part of the obstructed area very soon undergoes degenerative changes, and rapidly becomes decolourized. This necrosed area forms the pale infarct. Absorption of this infarcted zone is carried on by means of leucocytes and other phagocytic cells, and by new blood-vessels. If absorption be not complete the mass undergoes caseation and becomes surrounded by a capsule of fibrous tissue - being sharply cut off from the healthy tissue.

Where the malnutrition is the effect of poorness in the quality of the blood, the results are of course more widespread. The muscles suffer at an early period: they fall off in bulk, and later suffer from fatty degeneration, the heart being probably the first muscle to give way. Indeed, all tissues when under-nourished, either locally as the result of an ischaemia, or generally as from some impairment of the blood, such as that prevailing in pernicious anaemia, tend to suffer from fatty degeneration; and at first sight it seems somewhat remarkable that under-nourished tissues should develop fat in their substance (figs. 26 and 27, Pl. II.). The fatty matter, however, it must be borne in mind, is the expression of dissimilation of the actual substance of the proteids of the tissues, not of the splitting up of proteids or other carbonaceous nourishment supplied to them.

A part deprived of its natural nerve-supply sooner or later suffers from the effects of malnutrition. When the trigeminus nerve is divided (Majendie), or when its root is compressed injuriously, say Iby a tubercular tumour, the cornea begins to show points of ulceration, which, increasing in area, may bring about total disintegration of the eyeball. The earliest interpretation put upon this experiment was that the trophic influence of the nerve having been withdrawn, the tissue failed to nourish itself, and that degeneration ensued as a consequence. The subsequent experiments of Snellen, Senftleben, and, more lately, of Turner, seem to show that if the eyeball be protected from the impingement of foreign particles, an accident to which it is liable owing to its state of anaesthesia, the ulceration may be warded off indefinitely. If the eyeball be kept perfectly clean and no organism be admitted from the outside then ulceration will not follow. If, on the other hand, any pathogenic organisms be present the results are disastrous because the tissue, deprived of its nervous trophic supply, has greatly lessened resistance. The bed-sores which follow paralysis of the limbs are often quoted as proof of the direct trophic action of the nerve-supply upon the tissues, yet even here the evidence is somewhat contradictory. Still, there are facts which, for want of a better explanation, we are almost bound to conclude are to be accounted for on the direct nerve-control theory. The common variety of bed-sore is the result of continuous pressure on and irritation of the skin, the vitality and resisting power of which are lowered by a lesion of the cord cutting off the trophic supply to the skin affected. The acute bed-sore is, in some cases, a true trophic lesion occurring, as it may, on parts not subjected to continuous pressure or irritation. Trophic disturbance in the nutrition of the skin may be so great that a slight degree of external pressure or irritation is sufficient to excite even a gangrenous inflammation. Again, a fractured bone in a paralysed limb often fails to unite, while another in the opposite sound limb unites readily, and an ulcerated surface on a paralysed limb shows little healing reaction. A salivary gland degenerates when its nerve-supply is cut off; and the nerves leading up to the symmetrical sloughs in Raynaud's disease have been found in an advanced state of degeneration (Affleck and Wiglesworth). It is just a question, however, whether, even in instances such as these, the nutritional failure may not be explained upon the assumption of withdrawal of the local vasomotor control. There seems to be little doubt, notwithstanding, that one of the chief functions of the nerve cell is that of the propagation of a trophicj influence along its axon. When a nerve-trunk is separated from its central connexion, the distal portion falls into a state of fatty degeneration (Wallerian or secondary degeneration). That special trophic nerves, however, exist throughout the body, seems to be a myth. It is much more likely, as Verworn alleges, that the nerves which influence the characteristic function of any tissue regulate thereby the metabolism of the cells in question - in other words, that every nerve serves as a trophic nerve for the tissues it supplies. It is a significant fact that neoplasms contain very few nerve-fibres, even although growing luxuriantly, and there is a doubt whether the few twigs contained in them may not merely have been dragged into their midst as the tumour mass expanded (Young).

Overwork

The effect of overwork upon an organ or tissue varies in accordance with (a) the particular organ or tissue concerned, (b) the amount of nourishment conveyed to it, and (c) the power of assimilation possessed by its cells. In the case of muscle, if the available nourishment be sufficient, and if the power of assimilation of the muscle cells remain unimpaired, its bulk increases, that is to say, it becomes hypertrophied.

It may be advisable to define exactly what is meant by " hypertrophy," as the term is often used in a loose and insignificant sense. Mere enlargement of an organ does not imply that it is in a state of hypertrophy, for some of the largest organs met with in morbid anatomy are in a condition of extreme atrophy. Some organs are subject to enlargement from deposition within them of a foreign substance (amyloid, fat, &c.). This, it need hardly be said, has nothing to do with hypertrophy. The term hypertrophy is used when the individual tissue elements become bigger to meet the demands of greater functional activity; hyperplasia, if there is an increase in the number of these elements; and pseudo-hypertrophy, when the specific tissue element is largely replaced by another tissue.

There are conditions in which we have an abnormal increase in the tissue elements but which strictly should not be defined as hypertrophies, such as new-growths, abnormal enlargements of bones and organs due to syphilis, tuberculosis, osteitis deformans, acromegaly, myxoedema, &c. The enormously long teeth sometimes found in rodents also are not due to hypertrophy, as they are normally endowed with rapid growth to compensate for the constant and rapid attrition which takes place from the opposed teeth. Should one of these teeth be destroyed the opposed one loses its natural means of attrition and becomes a remarkable, curved tusk-like elongation. The nails of the fingers, or the hair of the scalp may grow to an enormous length if not trimmed.

True hypertrophy is commonly found in the hollow muscular organs such as the heart, bladder and alimentary canal. As any obstruction to the outflow of the contents throws an increased amount of work on the walls, in order to overcome the resistance, the intermittent strain, acting on the muscle cells, stimulates them to enlarge and proliferate, fig. 28, Pl. II., and gives rise to adaptive hypertrophy. Should there be much loss of tissue of an organ, the cells of the remaining part will enlarge and undergo an active proliferation (hyperplasia) so that it may be made up to the original amount. Or again, in the case of paired organs, if one be removed by operation, or destroyed by disease, the other at once undertakes to carry on the functions of both. To do so a general enlargement takes place until it may reach the size and weight equal to the original pair. This is known as compensatory hypertrophy.

Examples of physiological hypertrophy are found in the ovaries, uterus and mammary glands, where there is an increased functional activity required at the period of gestation. Local hypertrophy may also be due to stimulation resulting from friction or intermittent pressure, as one may see in the thickenings on the skin of the artisan's hands. The extreme development of the muscles in the weightlifting athlete and in the arm of the blacksmith is the result of increased functional activity with a corresponding increase in the vascular supply; this exercise may produce an over-development so excessive as to be classed as abnormal.

In atrophy we have a series of retrograde processes in organs and tissues, which are usually characterized by a progressive diminution in size which may even end in their complete disappearance (fig. 29, Pl. II.). This wasting may be general or local - continuously from the embryonic period there is this natural process of displacement and decay of tissues going on in the growing organism. The functions of the thymus gland begin to cease after the second year from birth. The gland then slowly shrinks and undergoes absorption. From atrophy of their roots, caused by the pressure of the growing permanent teeth, the " milk teeth " in children become loose and are cast off. The ovaries show atrophic changes after the menopause. In old age there is a natural wearing out of the elements of the various tissues. Their physiological activities gradually fail owing to the constructive processes having become so exhausted from long use that the destructive ones are able to overtake them. As the cell fails and shrinks, so does it become more and more unable to make good the waste due to metabolism. This physiological wasting is termed senile atrophy.

General atrophy or emaciation is brought about by the tissues being entirely or partially deprived of nutriment, as in starvation, or in malignant, tubercular, and other diseases of the alimentary system which interfere with the proper ingestion, digestion or absorption of food material. The toxic actions produced in continued fevers, in certain chronic diseases, and by intestinal parasites largely aid in producing degeneration, emaciation and atrophy.

Atrophy may follow primary arrest of function - disuse atrophy. The loss of an eye will be followed by atrophy of the optic nerve; the tissues in a stump of an amputated limb show atrophic changes; a paralysed limb from long disuse shows much wasting; and one finds at great depths of the sea fishes and marine animals, which have almost completely lost the organs of sight, having been cut off for long ages from the stimuli (light) essential for these organs, and so brought into an atrophic condition from disuse.

Atrophy may also follow from overwork. Increased work thrown on to a tissue may produce hypertrophy, but, if this excessive function be kept up, atrophy will follow; even the blacksmith's arm breaks down owing to the hypertrophic muscle fibres becoming markedly atrophied.

From these causes a certain shrinkage is liable to occur, more evident in some parts of the body than in others. Thus the brain falls off in bulk, and the muscles become attenuated, and in no muscle is this more notable than in the case of the heart. A tendency to pigmentation also develops in certain tissues of the body, such as the nerve and muscle cells. As a result of these various degenerations the functions of the body deteriorate, the faculties become blunted, and the muscular energy of the body is below what it was in earlier life, while the secreting glands in certain instances become functionally obsolescent.

Continuous Over-pressure

The tissues of an animal or plant are all under a certain pressure, caused, in the one case, by the expulsive action of the heart and the restraint of the skin and other elastic tissues, and, in the other case, by the force of the rising sap and the restraint of the periderm or bark. Under this normal amount of pressure they can live and grow. But when- -ever, from any cause, the degree of pressure which they are naturally intended to withstand is surpassed, they fail to nourish themselves, become granular, die, and, falling to pieces, are absorbed.

Deleterious Surroundings

There can be little doubt that all unnatural and artificial modes of life tend to deterioration of the powers of resistance of the organism to disease. We see it exemplified in plant life in circumstances which are unnatural to the life of the plant, and the prevalence of certain constitutional tendencies among the inhabitants of crowded cities bears evidence to the same law.

Man, like other animals, was naturally intended to lead an outdoor life. He was originally a hunter and a tiller of the ground, breathing a pure atmosphere, living on a frugal diet, and exercising his muscles. Whenever these conditions are infringed his powers of resistance to disease are lessened, and certain tendencies begin to show themselves, which are generally termed constitutional. Thus the liability to tubercular infection is far commoner in the midst of a depraved population than in one fulfilling the primary laws of nature; rickets is a disease of great cities rather than of rural districts; and syphilis is more disastrous and protracted in its course in the depraved in health than in the robust. Cattle kept within-doors are in a large proportion of cases tubercular, while those leading an outdoor life are much less liable to infection. The improvement which has taken place in the general health of the inhabitants of cities during recent years, concurrent with hygienic legislation, is ample proof of the above assertions. The diminution in the number of deaths from tuberculosis during the last forty to fifty years of the 19th century of itself points in this direction. Every living organism, animal and vegetable, tends to maintain a normal state of health; it is when the natural laws of health are violated that the liability to disease begins to assert itself. If, in these circumstances, the food supply be also insufficient, the combination of influences is sure, in course of time, to bring about a physical deterioration of the race. Certain avocations have a direct and immediate influence in causing diseased states of body. Thus workers in lead suffer from the effects of this substance as a poison, those who work in phosphorus are liable to necrosis of bone and fatty degeneration of the blood vessels and organs, and the many occupations in which dust is inhaled (coalmining, stone-dressing, steel-polishing, &c.; fig. 30, Pl. III.) are fraught with the greatest danger, owing to the destructive influence exerted upon the lungs by the inhaled particles. Among the most dangerous of the last class (the pneumokonioses) is perhaps that in which the dust particles take the form of finely divided freestone, as in stone-dressing and the dry-polishing on the grindstone of steel. The particles in this case set up a form of fibrosis of the lung, which, either of itself or by rendering the organ liable to tubercular infection, is extremely fatal. The abuse of alcohol may also be mentioned here as a factor in the poduction of disease.

Parasitism

Of all external agents acting for evil, however, probably vegetable and animal micro-organisms with a pathogenic bent are most to be feared. When we consider that tuberculosis, diphtheria, cholera, tetanus, typhoid fever, anthrax, malaria and a host of other contagious diseases have each been proved to be of parasitical origin, an idea may be conve y ed of the range of the subject. The living organism may be regarded as constantly engaged in a warfare with these silent and apparently insignificant messengers of destruction and death, with the result that too often the battle ends in favour of the attacking enemy.

Heredity

The tendencies to disease are in great part hereditary. They probably express a variation which may have occurred in a far-back ancestor, or in one more recent, and render the individual vulnerable to the attacks of parasitic fungi, or, it may be, become manifest as errors of metabolism. The psychopathic, the tubercular, the rickety, and the gouty constitution may all be transmitted through a line of ascendants, and only require the necessary exciting agents to render them apparent. A distinction must be drawn between the above and diseases, like syphilis and small-pox, in which the contagion of, not the tendency to, the disease is transmitted directly to the foetus in utero. (See Heredity.) The Cellular Doctrine In Pathology The cellular pathology is the pathology of to-day; indeed, protoplasm - its vital characteristics under abnormal influences and its decay - will be regarded most likely as the basis of pathology in all time. According to our present knowledge of physiological and pathological processes, we must regard the cell as the ultimate biological unit - a unit of structure and a unit of function; this was first put forward by Schleiden in 1838, and by Schwann in 1839, but we owe to Virchow the full recognition of the fundamental importance of the living cell in all the processes of life, whether in health or disease. When Virchow wrote, in 1850, " every animal presents itself as a sum of vital unities, every one of which manifests all the characteristics of life," he expressed a doctrine whose sway since then has practically been uninterrupted. The somatic cells represent communities or republics, as it were, which we name organs and tissues, but each cell possesses a certain autonomy and independence of action, and exhibits phenomena which are indicative of vitality.

Still, it must be borne in mind that this alleged autonomy of action is said to be founded upon an erroneous supposition, on the supposition that each cell is structurally, and it may be said functionally, separated from those in its neighbourhood. It is well known that in the vegetable kingdom the protoplasm of one cell frequently overflows into that of cells adjacent - that there is, as it were, a continuous network of protoplasm (idioplasm of Nageli) prevailing throughout vegetable tissues, rather than an aggregation of isolated units. The same inter-communication prevails between adjacent cells in some animal tissues, and more particularly in those which are pathological, as in the case of the epithelial cells of cancer. Assuming, with Sedgwick and others, this amassed and bound condition of the tissues to be true, it would be necessary to reject the cell-doctrine in pathology altogether, and to regard the living basis of the organism as a continuous substance whose parts are incapable of living independently of the whole. Until, however, further evidence is forthcoming in support of this syncytial theory of structure, it would be unwise to regard it as established sufficiently to constitute a serviceable working hypothesis; hence, for the time being, we must accept the assertion that the cell represents the ultimate tissue-unit. Our present day definition of a cell is a minute portion of living organized substance or protoplasm.

The cells met with in morbid parts which are in a state of active vitality are built up of the same components as those Structure of found in normal tissues (Pl. I.). 1 Thus they are pro vided with a nucleus which is the centre of cell activity; Pathological both of the reproductive and chemical (metabolic) pro- GelIs. cesses which occur in the cell protoplasm. The executive centre 1 Description Of Plate I. Series Of Figures Illustrative Of I Rregula Rdivision Of Cells.

Figs. 1 to 6 are from the epithelial cells of a cancer of the mamma, (After Galeotti.) „ 7 to 21 are from a sarcoma. (After Trambusti.) FIG. I. - Resting epithelial cell.

varies in shape, but is usually round or oval, and is sharply defined by a nuclear membrane from the cytoplasm in which it lies. The nucleus in its vegetative stage shows a fine network throughout containing in the meshes the so-called nuclear-sap; attached to the network are the chromosomes, in the form of small irregular masses, which have a strong affinity for the " basic dyes." Embedded in the nucleus are one or more nucleoli (plasmosomes) having an affinity for the " acid dyes." The nucleolus shows an unstainable point at the centre known as the endonucleolus or nucleoluolus (Auerbach).

The cell body, or cytoplasm, is apparently composed of a fine reticulum or network, containing within the meshes a soft viscid, transparent substance, the cell-sap, or hyaloplasm, which is probably a nutrient material to the living cell. Within the cytoplasm are found manifestations of functional activity, in the form of digestive vacuoles, granules, fat, glycogen, pigment, and foreign bodies. Usually the cytoplasm shows a marked affinity for the acid stains, but the different bodies found in the cell may show great variation in their staining reactions.

The centrosomes which play so important a part in cell division may be found either lying within or at one side of the nucleus in the vegetative condition of the cell. Centrosomes may be single, but usually two are lying close together in the attraction-sphere. When mitosis is about to take place, they separate from one another and pass to the poles of the nucleus, forming the achromatic spindle. After the division and cleavage of the chromosomes of the original nucleus have taken place they pass from the equator to the poles of the spindle, rearranging themselves close to the separated centrosomes to form daughter nuclei.

The cytoplasm of the cell now undergoes division in a line between the two daughter nuclei. When complete separation has taken place, we have two daughter cells formed from the original, each being a perfect cell-unit. Some pathological cells, such as the giant-cells of tumours, of bone, and those of tubercle, are polynucleated; in some instances they may contain as many as thirty or more nuclei. The only evidence we have in pathology of living structures in which apparently a differentiation into cell-body and nucleus does not exist, is in the case of bacteria, but then there comes the question whether they may not possess chromatin distributed through their substance, in the form of metachromatic points, as is the case in some infusoria (Trachelocerca, Gruber).

Although the methods of cell-division prevailing in normal structures are maintained generally in those which are pathological, yet certain modifications of these methods are more noticeable in the latter than in the former. Thus in the neoplasmata direct cell-division is more the rule than in healthy parts. In actively growing neoplasmata, certainly, the indirect method prevails largely, but seems to go on side by side with the direct.

A curious and interesting modification of the indirect method, known as " asymmetrical division," occurs frequently in epitheliomata, sarcomata, &c. (Hansemann). It consists in an unequal number of chromosomes passing over to each of the daughter nuclei, so that one may become hypochromatic, the other hyperchromatic. When this happens the resulting cleavage of the cytoplasm and nucleus is also unequal. Several explanations have been given of Fig. 2. - Asymmetrical diaster.

3

Tripolar division in which the splitting of the loops has commenced.

4

Tetrapolar karyokinesis.

5

Another form of tetrapolar division.

6

Cell in a state of degeneration and chromatolysis; the large rounded body in the cell is a cancer parasite. 7. - Polynucleated cell with nuclei of normal size arising from multiple karyokinetic division.

8

Pigmented cell with resting nucleus. The attraction-sphere and centrosome lie in the cytoplasma in the neighbourhood of the nucleus.

9

Hypertrophic nucleolus.

to

Large cell with a single nucleus; nucleoli in a state of degeneration.

I I. - Multinucleated giant-cell, the nuclei small and produced amitotically.

12

Karyokinetic figure, the one centrosome much larger than the other.

13

Cell in process of karyokinetic division with retention of the nucleolus during the division.

14

Division of the nucleolus and formation of nuclear plate. The nucleolus is elongated, and its longest measurement lies in the direction of the equatorial plane of the nucleus.

15

Division of the nucleolus by elongation, construction, and equilateral division of the nucleus.

16

Division of the nucleolus without any evidence of division of the nucleus.

17

Nucleus with many nucleoli.

18

Direct division of nucleus.

19

Multiple direct division of the nucleus.

20

Nail-like nucleolus.

2 I. - Fragmentation of the nucleus.

the meaning of these irregularly chromatic cells, but that which most lends itself to the facts of the case seems to be that they represent a condition of abnormal karyorhexis.

In many pathological cells undergoing indirect segmentation, centrosomes appear to be absent, or at any rate do not manifest themselves at the poles of the achromatic spindle. When they are. present, that at one end of the spindle may be unusually large, the other of natural size, and they may vary in shape. In pathological cell-division it happens occasionally that the segmentation of the cytoplasm is delayed beyond that of the mitotic network. The daughter nuclei may have arrived at the anaphase stage, and have even gone the length of forming a nuclear membrane, without an equatorial depression having shown itself in the cell-body. Sometimes the equatorial depression fails entirely, and the separation, as in some vegetable cells, takes place through the construction of a cell-plate. Intranuclear plexuses are not usually found in giantcells, but have been described in the giant-cells of sarcomata by Klebs and Hansemann, and in those of tubercle by Baumgarten. Some of the nuclei within multinucleated cells may occasionally be engaged in mitotic division, the others being in the resting state.

In the earlier accepted notion of direct segmentation, usually known as the schema of Remak, division was described as commencing in the nucleolus, as thereafter spreading to the nucleus, and as ultimately implicating the cell-substance. Trambusti, curiously, finds confirmatory evidence of this in the division of cells in sarcoma. Contrary, however, to the experience of others, he has never found that the attraction-spheres play an important part in direct cell-division, or, indeed, that they exert any influence whatever upon the mechanism of the process. Where pigment was present within the cells (sarcoma), the attraction-spheres were represented by quite clear unpigmented areas, sometimes with a centrosome in their midst.

Repair Of Injuries In the process of inflammation we have a series of reactions on the part of the tissues, and fluids of the body, to counteract the ill effects of irritation or injury, to get rid of the cause, and to repair its results. Injury and loss of tissue are usually followed by repair, and both the destructive and reparative changes are, as a rule, classified under the term inflammation. The irritants may be bacteria and their toxins, or they may be mechanical, chemical or thermic.

We do not now concur with the old view that inflammation was essentially an injurious process; rather do we look upon it as beneficial to the organism. In the various reactions of the tissues against the exciting cause of the injury we see a striking example of a beautifully organized plan of attack and defence on the part of the organism.

In some of the infective conditions the conflict fortifies the organism against future attacks of the same nature, as for example in the immunity following many of the acute infective diseases. This acquired immunity is brought about by the development of a protective body as a result of the struggle of the cells and fluids of the body with the invading bacteria and their toxins. This resistance may be more or less permanent. If the invasion is due to a pus-producing micro-organism which settles in some local part of the body, the result is an abscess (fig. 25, Pl. II.).

Abscesses

One can easily demonstrate all the actions and reactions which take place in this form of acute inflammation. In such a conflict one can see the presence of these minute but dangerous foes in the tissues. At once they proceed to make good their hold on the position they have secured by secreting and throwing out toxins which cause more or less injury to the tissues in their immediate neighbourhood. These micro-organisms having found in the tissues everything favourable for their needs, rapidly multiply and very soon produce serious results. At this point one's attention is focused on the wonderful reactions possessed by the healthy tissues to combat these evil influences.

In a very short period - within three or four hours after infection - there appears to have been a message conveyed to the defenders of the body both as to the point of attack and the nature of the invasion. There is thus brought into play a series of processes on the part of the tissues - the vascular inflammatory changes - which is really the first move to neutralize the malign effects. We find at this early stage oedema of the part. This is an increased exudation of fluid from the engorged blood vessels which not only dilutes the toxins, but is supposed to contain substances which in some way act on these living micro-organisms and render them a more easy prey to the polymorpho-nuclear leucocytes (fig. 23, Pl. II.) - cells that are motile and extremely phagocytic to these bacteria. At this stage the Drawn by Rd. Muir. Niagara Litho. Co., Buffalo. N. 1 rapidity of the blood circulation has become greatly diminished. The polymorpho-nuclear leucocytes are seen in great numbers in the blood vessels.

In health these cells, belonging to our first army of defenders, are found continually circulating in the blood stream in fairly large numbers; they are ever ready to rush to the point of attack, where they at once leave the blood stream by passing through the vessel walls - emigration - into the tissues of the danger zone. There they show marked phagocytosis, attacking and taking up into their interior and destroying the micro-organisms in large numbers. At the same time large numbers of these cells perish in the struggle, but even the death of these cells is of value to the body, as in the process of breaking down there are set free ferments which not only act detrimentally to the bacteria, but also may stimulate the bringing forward of another form of cell defenders - the mononuclear leucocyte.

To replace this cellular destruction there has been a demand for reinforcements on the home centres of the polymorpho-nuclear leucocytes - the bone marrow. This call is immediately answered by an active proliferation and steady maturing of the myclocytes in the marrow to form the polymorpho-nuclear leucocytes. These then pass into the blood stream in very large numbers, and appear to be specially attracted to the point of injury by a positive chemiotactic action. This phenomenon, called chemiotaxis, has been studied by several investigators. Leber experimented with several chemical compounds to find what reaction they had on these cells; by using fine glass tubes sealed at the outer end and containing a chemical substance, and by introducing the open end into the blood vessels he found that the leucocytes were attracted - positive chemiotaxis - by the various compounds of mercury, copper, turpentin, and other substances. That quinine, chloroform, glycerin, alcohol, with others, had no attractive influence on them - negative chemiotaxis. It was also found that a weak solution may have a marked positive attraction whilst a strong solution of the same substance will have the opposite effect. It has been proved that the pyo-genic bacterial toxins, if not too concentrated, will attract the polymorpho-nuclear leucocytes, but if concentrated, may have a repelling influence.

Then we have the property of adaptation, in which the negative reaction may be changed into a positive; a given toxin may at first repel the cell, but by a gradual process the cell becomes accustomed to such a toxin and will move towards it.

On reaching the vicinity they leave the blood stream and join in the warfare - many performing their function of phagocytosis (q.v.), others falling victims to the toxins. The tissues of the part become disorganized or destroyed, and their place is taken by the mass of warring cellular elements now recognized as pus.

As soon as the fluids and the polymorpho-nuclear leucocytes have :succeeded in diminishing the virulence of the micro-organism, the second line of defenders - the large mononuclear leucocytes (fig. 23, Pl. II.) make their appearance at the field of battle in ever increasing numbers. These are amoeboid cells and are extremely phagocytic, their power of digestion being greatly developed. Their principal function is to bring about the removal of foreign, dead or degenerating material. This they take up into their protoplasm, where it is rapidly digested by being acted on by some intracellular digestive ferment (fig. 31, Pl. III.). Where the material is too large to be taken up by an individual cell, the dissolution is brought about by the cells surrounding the material, to which they closely apply themselves, and by the secreting of the ferment, a gradual process of erosion is brought about with ultimate absorption.

If the abscess be deeply situated in some tissue and not able to open on to a free surface so allowing the contents to be drained off, the phagocytic cells play a very prominent part in the resolution of the abscess. They are seen pushing their way right into the field of ,conflict and greedily ingesting both friends and foes. The first defenders, the polymorpho-nuclear leucocytes, having performed their functions, are of no more use to the organism and are therefore removed by the mono-nuclear phagocytes as useless material (fig. 31, Pl. III.).

The tissues having now mobilized an army that completely :surrounds the fighting zone, there is a gradual and general advance made from all sides. The vanguard of this advancing army is composed of a more or less compact layer of the mono-nuclear phagocytes (polyblasts) accompanied by numerous new vessels. These phagocytic cells carry out the complete removal of all the injured warring elements and the damaged tissues of the part. The vessels are only temporary channels by which is brought forward the food supply that is needed by the advancing army if it is suc- ,cessfully to carry on its function; they probably also drain off the deleterious fluid substances formed by the cellular disintegration that has taken place in the part. Closely on the advance of this .army of phagocytes or scavenger cells follows the third line of defenders, the connective tissue cells or fibroblasts.

All these cells are probably of local origin and are now stimulated to make good the damage. The connective tissue cells or fibroblasts (fig. 32, Pl. III.) are seen in active proliferation around the phagocytic :zone. First they are round or oval in shape; later they become spindle shaped, arranging themselves in layers. Then they develop .definite fibrils which differentiate into fibrous laminae forming a zone which shuts off the abscess from the healthy tissue and so prevents the further invasion and injurious effects of the microorganism. By the aid of the new fibroblasts this fibrous tissue zone gradually encroaches on the pus area and replaces the phagocytic layer of cells as they proceed with the absorption of the pus mass (fig. 33, Pl. III.). When complete removal of the pus mass has been accomplished by the process of absorption, the damaged area is replaced by the new fibrous tissue, which later becomes condensed and forms the cicatricial or scar tissue (fig. 35, Pl. III.) - a healed abscess.

Wounds

The healing of wounds is brought about by similar processes to that seen in the evolution of an abscess.

If the injury be a small incised wound through the skin and subcutaneous tissues without any septic contamination, there usually follows a minimum of reaction on the part of the tissues. As the edges of the wound are brought into accurate apposition there is little or no blood lodged between them, so that an extremely narrow strip of fibrin glues the cut edges together. This strip is rapidly replaced, mainly by the connective tissue cells of the adjoining tissue growing across the temporary filled breach and firmly uniting the two cut surfaces. The vascular changes are practically absent in healing by first intention.

Healing by second intention, or granulation, is usually seen where there has been loss of tissue, or extensive damage. The reactions of the tissues vary in degrees according to the nature and severity of the injury. In resenting such insults, a remarkable uniformity and regularity in the processes is brought about by the different cells and fluids of the healthy tissues of the body. Although we have not reached a stage of certainty regarding their origin, function and destiny, recent investigations have brought forward evidence to elucidate the importance of the part played by the different cells in the various types of the inflammatory process.

If there be a loss of tissue brought about by severe in j ury to the skin and the deeper tissues, there is usually an extravasation of blood from the severed vessels. Along with the exuded serum this fills up the breach in the tissues and the whole is rapidly formed into a fibrinous mass due to the disintegration of the polymorphonuclear leucocytes setting free their ferment. The ferment thus set free brings about the coagulation of the serum, which acts as a protective and temporary scaffolding to the injured tissues. Lying between the fibrin mass and the healthy tissues is a zone of injured and degenerated tissue elements, the result of the trauma.

As early as six hours after the injury the polymorpho-nuclear leucocytes are seen passing in large numbers from the dilated and congested blood vessels of the tissues at the margin of the wound into the injured zone, where they carry on an active phagocytosis. It is believed also that they secrete bactericidal substances and ferments which bring about the liquefaction of the fibrin and the damaged tissues - histolysis - and thus assist the process of absorption. They appear to prepare the injured zone for the coming of the next series of cells. Their function being at an end they give way to these cells which carry on the process of absorption.

In a period varying from twenty-four to thirty hours there is marked evidence of the removal of the degenerated cellular elements in the damaged zone by the mono-nuclear phagocytes. Numerous fibroblasts, together with polyblasts, are visible in the fibrin mass, and the vessels at the periphery of the damaged zone are now seen to be sending out offshoots which assist in the process of absorption. These vascular buds grow out in various directions as little solid projections of cells; they then become channelled and form the new but temporary meshwork.

After two to four days these processes are more clearly emphasized. By these processes we reach the stage where the fibrin mass and damaged tissues have been completely removed, and replaced by a temporary vascular and cellular tissue, known as granulation tissue (fig. 34, Pl. III.), which in turn has to give way to the more firm and differentiated fibrous tissue. By this time the skin epithelium may have grown over the wound.

After five to seven days we find the connective tissue cells taking the principal part in the building up of the new permanent tissue, for at this stage there is an active proliferation of the fibroblasts. These cells of various shapes are seen in large numbers, mainly lying in a direction parallel to the new vessels and capillaries, which all run at right angles to the wound surface. The branching processes of these cells apparently anastomose with one another and form a delicate supporting network. It is from these cells that the fine fibrillar substance is formed, and from this stage onwards - eight to fifteen days - there is a steady increase in the new fibrils, giving more density to the new tissue. At the same time there is brought about an alteration in the arrangement of the position of the fibroblasts. These become spindle shaped with their long axis more and more assuming a position at right angles to the vessels (fig. 34, Pl. III.); the two edges of the wound are thus more firmly bound together. As their fibrils become more developed they gradually form fibrous laminae which are laid down first in the deeper part of the wound. When this process has reached a certain stage and all the absorption necessary has occurred the new blood vessels, from the increasing pressure of the successive fibrous layers, gradually dwindle and become obliterated, i.e. at a period corresponding to the condensation of the fibrous laminae and the disappearance of the cellular character of the granulation tissue. Thus is formed in the damaged area a permanent tissue known as scar tissue (fig. 35, P1. III.).

Fibrosis

Where a chronic inflammatory process has taken possession of an organ, or, let us say, has been located in periosteum or other fibrous part, there is a great tendency to the production of cicatricial fibrous tissue in mass. Thus it is laid down in large quantity in cirrhosis of the liver, kidney or lung, and reacts upon these organs by contracting and inducing atrophy. The term " cirrhosis " or " fibrosis " is usually applied to such a condition of organs (figs. 36 and 37, Pl. IV.), that of " sclerosis " is used when such a deposition of fibrous tissue occurs within the central nervous system. Gull and Sutton asserted that in particular states of body, and more especially in the condition associated with cirrhotic kidney, such a fibrosis becomes general, running, as they alleged it does, along the adventitia of arteries and spreading to their capillaries. They supposed that it was accompanied by a peculiar hyaline thickening of the arterial wall, usually of the tunica intima, and hence they termed the supposed diseased state " arterio-capillary fibrosis," and gave the fibrous substance the name " hyaline-fibroid." They held that the cirrhotic kidney is simply a local manifestation of a general fibrous disease. Their theory, however, has fallen into disfavour of late years.

Tumours Or New Growths The various definitions of the term " new growth " leave us with a definite conception of it as a new formation of tissue which appears to originate and to grow independently. We have already compared the body to a social community, each constituent element of which - the cell - lives its own life but subordinates its individuality to the good of the whole organism. The essential characteristic of a new growth is that this subordination is lost and the tissue elements, freed from the-normal mutual restraint of their interdependence, give way to an abnormal growth. All the hypotheses about the causation of new growths seek to explain the secret of this individuality or " autonomy," as they recognize that the mystery of the origin of the great majority of tumours would be solved if we could trace how or why the tissue elements in which they develop first took on this abnormal growth.

Tumours are divided into two main groups - innocent and _malignant. These differ only in degree and there is no hard and fast line between them. Innocent tumours are usually sharply defined from the surrounding tissues, and show no tendency to spread into them or to pass by means of lymphatics and bloodvessels to neighbouring parts (fig. 38, Pl. IV.). Malignant tumours, on the other hand, invade the adjacent tissues and pass by lymphatics and blood vessels to distant parts, where they set up secondary growths (fig. 39, Pl. IV.).

Tumours appear to arise spontaneously, i.e. without evident cause; they may develop in association with prolonged irritation or injury (later referred to in more detail). To heredity, as an indirect or predisposing cause, has probably been assigned too great importance, and the many facts brought forward of the relative frequency of cancer in members of one family only justify the conclusion that the tissue-resistance of certain families is lowered.

At the present time we have still before us the question, what is the essential cause of tumours (q.v.) ? This, one of the most difficult problems of pathology, is being attacked by many able workers, who are all striving from different standpoints to elucidate the nature of these new formations, which spring from the normal tissues in which they develop and which they destroy. In spite of all the valuable research work that has been done within the last few years, the essential cause of new growths still remains unknown.

To the work carried on by the Imperial Cancer Research Fund in England, and to investigators in other countries, are due the present day scientific efforts made to systematize investigation and clear away many of the hypothetical speculations that have gathered round this most difficult subject. Their investigations on cancers found in the lower animals, and the successful transplantation of such growths into a new host of the same species (mice and rats), have greatly advanced our knowledge of the etiology of this disease.

Many of the hypotheses of the past put forward - to explain cancer must be discarded, in view of the facts brought to light by the comparative and experimental research of recent times. According to the hypothesis of Waldeyer and Thiersch there is perfect equilibrium between the normal epithelium and its supporting structure, the connective tissue, but with advancing age this balance is upset owing to the connective tissue gradually losing its restraining power. The epithelial cells are then able to pass from their normal position, in consequence of which they proliferate and at the same time revert to a more primitive type of cell. In this way they give rise to a malignant new growth.

Cohnheim's hypothesis of " embryonic residues " provides that early in the development of the embryo some of the cells, or groups of cells, are separated from their organic continuity during the various foldings that take place in the actively growing embryo. The separated cells become intermingled with other tissue elements amongst which they lie dormant with their inherent power of proliferation in abeyance. At a later date in the life of the individual, by some unknown stimuli, they resume their active power of proliferation and so give rise to new growths.

The " tissue-tension " hypothesis of Ribbert is a combination of the two foregoing. He holds that new growths arise, both before birth or at any subsequent period of life, by the separation of cells or clumps of cells from their normal position, and that in health there is a balance between the various tissues and tissue elements regulated by what he calls the " tissue-tension " of the part, i.e. that cells or groups of cells have a restraining power on one another which prevents any physiological over-activity.

From whatever cause the resisting power of the tissue elements is thus weakened, the invasion of other tissue elements is then allowed to take place. These being freed from the normal inhibiting power of the neighbouring elements, multiply and go on to the formation of a new growth. According to Ribbert it is the isolation, together with the latent capacity of isolated cells for unlimited poliferation, that gives rise to new growths.

Hansemann's "anaplasia " hypothesis seeks to find an explanation of the formation of new growths in the absence of the histological differentiation of the cell associated with a corresponding increase in its proliferative power and a suspension, or loss, of its functional activity.

The greater the degree of anaplasia the more the tumour cells conform in character and appearance to the embryonic type of cell and the more malignant is the new growth. A simple fibroma is a growth composed of fully formed fibrous tissue (fig. 40, Pl. IV.). The small round celled sarcoma is a malignant growth, and is composed of the primitive type of cell that goes to form fibrous tissue (fig. 41, Pl. IV.).

Then we have Beard's " germ-cell " hypothesis, in which he holds that many of the germ-cells in the growing embryo fail to reach their proper position - the generative areas - and settle down and become quiescent in some somatic tissue of the embryo. They may at some later date become active in some way, and so give rise to a cellular proliferation that may imitate the structure in which they grow, so giving rise to new growths.

Some workers regard certain appearances in dividing cells found in cancer as evidence of a reversion of the somatic cell to the germcell type (heterotypical), otherwise found only in the process which results in the formation of an embryo. These appearances are probably due toa pathological mitosis, commonly found in cancer, in which there is an irregular diminution in the number of chromosomes; some are cast out and become degenerated or some pass over to one of the daughter cells, leaving a reduced number in the other, and thus give rise to asymmetrical mitosis.

From the histological examination of tumour cells there is no evidence to show that they resemble the protozoal unicellular organisms in occasionally passing through a sexual process of reproduction, i.e. that nuclear conjugation between cells ever takes place.

In recent years the successful experimental transplantation of new growths, occurring sporadically in white mice and rats, into animals of the same species, has thrown a fresh light on all the features of malignant growths. From these experiments it is shown that cells taken from these growths and introduced into animals of the same species give rise to a cancerous growth, whose cells have acquired unlimited powers of proliferation. They are direct lineal descendants of the cells introduced, and are in no way formed from the tissue cells of the host in which they are placed and grow.

Not only is this true of epithelial cells, but - the connective tissuecells of the supporting structure of cancerous growth, after repeated transplantation, may become so altered that a gradual evolution of apparently normal connective tissue into sarcomatous elements takes place, these giving rise to " mixed tumours." The sarcomatous development may even completely outgrow the epithelial elements and so form and continue to grow as a pure sarcoma.

The fact that it is possible to propagate these cells of one animal for years in other animals of the same species, without any loss of their vegetative vitality, suggests that this continued growth is kept up by a growth-stimulating substance present in the proper species of animal; this substance, however, has not the power of transforming the normal tissue into a cancerous one.