RUDOLF VIRCHOW
Rudolf Virchow, the son of a small farmer and shopkeeper, was born at Schivelbein, in Pomerania, on October 13, 1821. He graduated in medicine at Berlin, and was appointed lecturer at the University, but his political enthusiasm brought him into disfavour. In 1849 he was removed to Wurzburg, where he was made professor of pathology, but in 1856 he returned to Berlin as Professor and Director of the Pathological Institute, and there acquired world-wide fame. His celebrated work, "Cellular Pathology as based on Histology," published in 1856, marks a distinct epoch in the science. Virchow established what Lord Lister describes as "the true and fertile doctrine that every morbid structure consists of cells which have been derived from pre-existing cells as a progeny." Virchow was not only distinguished as a pathologist, he also gained considerable fame as an archæologist and anthropologist. During the wars of 1866 and 1870–71, he equipped and drilled hospital corps and ambulance squads, and superintended hospital trains and the Berlin military hospital. War over, he directed his attention to sanitation and the sewage problems of Berlin. Virchow was a voluminous author on a variety of subjects, perhaps his most well-known works being "Famine Fever" and "Freedom of Science." He died on September 5, 1902.
The Cell and the Tissues
The chief point in the application of Histology to Pathology is to obtain recognition of the fact that the cell is really the ultimate morphological element in which there is any manifestation of life.
In certain respects animal cells differ from vegetable cells; but in essentials they are the same; both consist of matter of a nitrogenous nature.
When we examine a simple cell, we find we can distinguish morphological parts. In the first place, we find in the cell a round or oval body known as the nucleus. Occasionally the nucleus is stallate or angular; but as a rule, so long as cells have vital power, the nucleus maintains a nearly constant round or oval shape. The nucleus in its turn, in completely developed cells, very constantly encloses another structure within itself—the so-called nucleolus. With regard to the question of vital form, it cannot be said of the nucleolus that it appears to be an absolute essential, and in a considerable number of young cells it has as yet escaped detection. On the other hand, we regularly meet with it in fully-developed, older forms, and it therefore seems to mark a higher degree of development in the cell.
According to the view which was put forward in the first instance by Schleiden, and accepted by Schwann, the connection between the three co-existent cell-constituents was long thought to be of this nature: that the nucleolus was the first to show itself in the development of tissues, by separating out of a formative fluid (blastema, cyto-blastema), that it quickly attained a certain size, that then fine granules were precipitated out of the blastema and settled around it, and that about these there condensed a membrane. In this way a nucleus was formed about which new matter gradually gathered, and in due time produced a little membrane. This theory of the formation of the cell is designated the theory of free cell formation—a theory which has been now almost entirely abandoned.
It is highly probable that the nucleus plays an extremely important part within the cell—a part less connected with the function and specific office of the cell, than with its maintenance and multiplication as a living part. The specific (animal) function is most distinctly manifested in muscles, nerves, and gland cells, the peculiar actions of which—contraction, sensation, and secretion—appear to be connected in no direct manner with the nuclei. But the permanency of the cell as an element seems to depend on nucleus, for all cells which lose their nuclei quickly die, and break up, and disappear.
Every organism, whether vegetable or animal, must be regarded as a progressive total, made up of a larger or smaller number of similar or dissimilar cells. Just as a tree constitutes a mass arranged in a definite manner in which, in every single part, in the leaves as in the root, in the trunk as in the blossom, cells are discovered to be the ultimate elements, so it is with the forms of animal life. Every animal presents itself as a sum of vital unities, every one of which manifests all the characteristics of life. The characteristics and unity of life cannot be limited to any one particular spot in an organism (for instance, to the brain of a man) but are to be found only in the definite, constantly recurring structure, which every individual element displays. A so-called individual always represents an arrangement of a social kind, in which a number of individual existences are mutually dependent, but in such a way that every element has its own special action, and even though it derive its stimulus to activity from other parts, yet alone affects the actual performance of its duties.
Between cells there is a greater or less amount of a homogeneous substance—the intercellular substance. According to Schwann, the intercellular substance was cyto-blastema destined for the development of new cells; I believe this is not so, I believe that the intercellular substance is dependent in a certain definite manner upon the cells, and that certain parts of it belong to one cell and parts to another.
At various times, fibres, globules, and elementary granules, have been regarded as histological starting-points. Now, however, we have established the general principle that no development of any kind begins de novo and that as spontaneous generation is impossible in the case of entire organisms, so also it is impossible in the case of individual parts. No cell can build itself up out of non-cellular material. Where a cell arises, there a cell must have previously existed (omnis cellula e cellula), just as an animal can spring only from an animal, and a plant only from a plant. No developed tissues can be traced back to anything but a cell.
If we wish to classify tissues, a very simple division offers itself. We have (a) tissues which consist exclusively of cells, where cell lies close to cell. (b) Tissues in which the cells are separated by a certain amount of intercellular substance. (c) Tissues of a high or peculiar type, such as the nervous and muscular systems and vessels. An example of the first class is seen in the epithelial tissues. In these, cell lies close to cell, with nothing between.
The second class is exemplified in the connective tissues—tissues composed of intercellular substance in which at certain intervals cells lie embedded.
Muscles, nerves, and vessels form a somewhat heterogeneous group. The idea suggests itself that we have in all three structures to deal with real tubes filled with more or less movable contents. This view is, however, inadequate, since we cannot regard the blood as analogous to the medullary substance of the nerve, or contractile substance of a muscular fasciculus.
The elements of muscle have generally been regarded as the most simple. If we examine an ordinary red muscle, we find it to be composed of a number of cylindrical fibres, marked with transverse and longitudinal striæ. If, now, we add acetic acid, we discover also tolerably large nuclei with nucleoli. Thus we obtain an appearance like an elongated cell, and there is a tendency to regard the primitive fasciculus as having sprung from a single cell. To this view I am much inclined.
Pathological tissues arise from normal tissues; and there is no form of morbid growth which cannot in its elements be traced back to some model which had previously maintained an independent existence in the economy. A classification, also, of pathological growths may be made on exactly the same plan as that which we have suggested in the case of the normal tissues.
Nutrition, Blood, and Lymph. Pus
Nutritive material is carried to the tissues by the blood; but the material is accepted by the tissues only in accordance with their requirements for the moment, and is conveyed to the individual districts in suitable quantities. The muscular elements of the arteries have the most important influence upon the quantity of the blood distributed, and their elastic elements ensure an equable stream; but it is chiefly the simple homogeneous membrane of the capillaries that influences the permeation of the fluids. Not all the peculiarities, however, in the interchange of nutritive material are to be attributed to the capillary wall, for no doubt there are chemical affinities which enable certain parts specially to attract certain substances from the blood. We know, for example, that a number of substances are introduced into the body which have special affinities for the nerve tissues, and that certain materials are excreted by certain organs. We are therefore compelled to consider the individual elements as active agents of the attraction. If the living element be altered by disease, then it loses its power of specific attraction.
I do not regard the blood as the cause of chronic dyscrasiæ; for I do not regard the blood as a permanent tissue independently regenerating and propagating itself, but as a fluid in a state of constant dependence upon other parts. I consider that every dyscrasia is dependent upon a permanent supply of noxious ingredients from certain sources. As a continual ingestion of injurious food is capable of vitiating the blood, in like manner persistent disease in a definite organ is able to furnish the blood with a continual supply of morbid materials.
The essential point, therefore, is to search for the local sources of the different dyscrasiæ which cause disorders of the blood, for every permanent change which takes place in the condition of the circulating juices must be derived from definite organs or tissues.
The blood contains certain morphological elements. It contains a substance, fibrine, which appears as fibrillac when the blood clots, and red and colourless blood corpuscles.
The red blood corpuscles contain no nuclei except at certain periods of the development of the embyro. They are lighter or darker red according to the oxygen they contain. When treated with concentrated fluids they shrivel; when treated with diluted fluids they swell. They are rather coin-shaped, and when a drop of blood is quiet they are usually found aggregated in rows, like rouleaux of money.
The colourless corpuscles are much less numerous than the red corpuscles—only one to 300—but they are larger, and contain nuclei. When blood coagulates the white corpuscles sink more slowly and appear as a lighter coloured layer on the top of the clot.
Pus cells are very like colourless corpuscles, and the relation between the two has been much debated. A pus cell can be distinguished from a colourless blood cell only by its mode of origin. If it have an origin external to the blood, it must be pus; if it originate in the blood, it must be considered to be a blood cell.
In the early stages of its development, a white blood corpuscle is seen to modify by division; but in fully-developed blood such division is never seen. It is probable that colourless white corpuscles are given to the adult blood by the lymphatic glands. Every irritation of a part which is freely connected with lymphatic glands increases the number of colourless cells in the blood. Any excessive increase from this source I have designated leucocytosis.
In the first months of the embryo the red cell multiplies by division. In adult life the mode of its multiplication is unknown. They, also, are probably formed in the lymphatic glands and spleen.
In a disease I have named leukæmia, the colourless blood cells increase in number enormously. In such cases there is always disease of the spleen, and very often of the lymphatic glands.
These facts can hardly, I think, be interpreted in any other manner than by supposing that the spleen and lymphatic glands are intimately concerned in the production of the formed elements of the blood.
By pyæmia is meant pus corpuscles in the blood. But most cases of so-called pyæmia are really cases in which there is an increase of white blood corpuscles, and it is doubtful whether such a condition as pus in the blood does ever occur. In the extremely rare cases, in which pus breaks through into the veins, purulent ingredients may, without doubt, be conveyed into the blood, but in such cases the introduction of pus occurs for the most part but once, and there is no persistent pyæmia. Even when clots in veins break down and form matter like pus, it will be found that the matter is not really pus, and contains no pus cells.
Chlorosis is a condition in which there is a diminution of the cellular elements of the blood, due probably to their deficient formation in the spleen and lymphatic glands.
The Vital Processes and Their Relation to Disease. Inflammation
The study of the histology of the nervous system shows that in all parts of the body a splitting up into a number of small centres takes place, and that nowhere does a single central point susceptible of anatomical demonstration exist from which the operations of the body are directed. We find in the nervous systems definite little cells which serve as centres of motion, but we do not find any single ganglion cell in which alone all movement in the end originates. The most various individual motor apparatuses are connected with the most various individual motor ganglion cells. Sensations are certainly collected in definite ganglion cells. Still, among them, too, we do not find any single ganglion cell which can be in any way designated the centre of all sensation, but we again meet with a great number of very minute centres. All the operations which have their source in the nervous system, and there certainly are a very great number of them, do not allow us to recognise a unity anywhere else than in our own consciousness. An anatomical or physiological unity has at least as yet been nowhere demonstrated.
When we talk of life we mean vital activity. Now, every vital action supposes an excitation or irritation. The irritability of the part is the criterion by which we judge whether it be alive or not. Our notion of the death of a part is based upon nothing more or less than this—that we can no longer detect any irritability in it. If we now proceed with our analysis of what is to be included in the notion of excitability, we at once discover, that the different actions which can be provoked by the influence of any external agency are essentially of three kinds. The result of an excitation or irritation may, according to circumstances, be either a merely functional process, or a more or less increased nutrition of the part, or a formative process giving rise to a greater or less number of new elements. These differences manifest themselves more or less distinctly according as the particular tissues are more or less capable of responding to the one or other kinds of excitation. It certainly cannot be denied that the processes may not be distinctly defined, and that between the nutritive and formative processes, and also between the functional and nutritive ones there are transitional stages; still, when they are typically performed, there is a very marked difference between them, and considerable differences in the internal changes undergone by the excited parts.
In inflammation all three irritative processes occur side by side. Indeed, we may frequently see that when the organ itself is made up of different parts, one part of the tissue undergoes functional or nutritive, another formative, changes. If we consider what happens in a muscle we see that a chemical or traumatic stimulus produces a functional irritation of the primitive fasciculi, with contraction of the muscle followed by nutritive changes. On the other hand, in the interstitial connective tissue which binds the individual fasciculi of the muscle together, real new formations are readily produced, commonly pus. In this manner the three forms of irritation may be distinguished in one part.
The formative process is always preceded by nutritive enlargement due to irritation of the part, and has no connection with irritation of the nerves. Of course there may be also an irritation of the nerves, but this, if we do not take function into account, has no causal connection with the processes going on in the tissue proper, but is merely a collateral effect of the original disturbance.
Besides these active processes of function, nutrition, and new formation, there occur passive processes. Passive processes are called those changes in cells whereby they either lose a portion of their substance, or are so completely destroyed, that a loss of substance, a diminution of the sum total of the constituents of the body is produced. To this class belong fatty degeneration of cells, affection of arteries, calcification, and ossification of arteries, amyloid degeneration, and so forth.
It will now be necessary to consider inflammation at more length. The theory of inflammation has passed through various stages. At first heat was considered as its essential and dominant feature, then redness, then exudative swelling; while the speculative neuropathologists consider pain the fons et origo of the condition.
Personally, I believe that irritation must be taken as the starting-point in the consideration of inflammation. We cannot conceive of inflammation without an irritating stimulus, and the first question is, what conception we are to form of such a stimulus.
An inflammatory stimulus is a stimulus which acts either directly or through the medium of the blood upon the composition and constitution of a part in such a way as to enable it to attract to itself a larger quantity of matter than usual and to transform it according to circumstances. Every form of inflammation with which we are acquainted may be explained in this way. It may be assumed that inflammation begins from the moment that this increased absorption of matters into the tissue takes place, and the further transformation of these matters commences.
It must be noticed that hyperæmia is not the essential feature of inflammation, for inflammation occurs in non-vascular as well as in vascular parts, and the inflammatory processes are practically the same in both instances.
Nor is inflammatory exudation the essential feature of inflammation. I am of the opinion that there is no specific inflammatory exudation at all, but that the exudation we meet with is composed essentially of the material which has been generated in the inflamed part itself, through the change in its condition, and of the transuded fluid derived from the vessels. If, therefore, a part possess a great number of vessels, and particularly if they are superficial, it will be able to furnish an exudation, since the fluid which transudes from the blood conveys the special product of the tissue along with it to the surface. If this is not the case, there will be no exudation, but the whole process will be limited to the occurrence in the real substance of the tissue of the special changes which have been induced by the inflammatory stimulus.
In this manner, two forms of inflammation can be distinguished, the purely parenchymatous inflammation, where the process runs its course in the interior of the tissue, without our being able to detect the presence of any free fluid which has escaped from the blood; and the secretory (exudative) inflammation, where an increased escape of fluid takes place from the blood, and conveys the peculiar parenchymatous matters along with it to the surface of the organs. That there are two kinds of inflammation is shown by the fact that they occur for the most part in different organs. Every parenchymatous inflammation tends to alter the histological and functional character of an organ. Every inflammation with free exudation generally affords a certain relief to the parts by conveying away from it a great part of the noxious matters with which it is clogged.
New Formations
I at present entirely reject the blastema doctrine in its original form, and in its place I put the doctrine of the continuous development of tissues out of one another. My first doubts of the blastema doctrine date from my researches on tubercle. I found the tubercles never exhibited a discernible exudation; but always organised elements unpreceded by amorphous matter. I also found that the discharge from scrofulous glands and from inflamed lymphatic glands is not an exudation capable of organisation but merely débris, developed from the ordinary cells of the glands.
Until, however, the cellular nature of the body had been demonstrated, it seemed necessary in some instances to postulate a blastema or exudation to account for certain new formations. But the moment I could show the universality of cells—the moment I could show that bone corpuscles were real cells, and that connective tissues contained cells—from that moment cellular material for the building of new formations was apparent. In fact, the more observers increased the more distinctly was it shown that by far the greater number of new formations arise from the connective tissue. In almost all cases new formations may be seen to be formed by a process of ordinary cell division from previously existing cells. In some cases the cells continue to resemble the parent cells; in other cases they become different. All new formations built of cells which continue true to the parent type we may call homologous new formations; while those which depart from the parent type or undergo degenerative changes we may designate heterologous. In a narrower sense of the word heterologous new formations are alone destructive. The homologous ones may accidentally become very injurious, but still they do not possess what can properly be called a destructive or malignant character. On the other hand, every kind of heterologous formation whenever it has not its seat in entirely superficial parts, has a certain degree of malignity, and even superficial affections, though entirely confined to the most external layers of epidermis, may gradually exercise a very detrimental effect. Indeed, suppuration is of this nature, for suppuration is simply a process of proliferation by means of which cells are produced which do not acquire that degree of consolidation or permanent connection with each other which is necessary for the existence of the body. Pus is not the solvent of cells: but is itself dissolved tissues. A part becomes soft and liquefies, while suppurating, but it is not the pus which causes this softening; on the contrary, it is the pus which is produced as the result of the proliferation of tissues.
A suppurative change of this nature takes place in all heterologous new formations. The form of ulceration which is presented by cancer in its latest stages bears so great a resemblance to suppurative ulceration that the two things have long since been compared. The difference between suppuration and suppuration lies in the differing duration of the life of different cells. A cancer cell is capable of existing longer than a pus corpuscle, and a cancerous tumour may last for months yet still contain the whole of its elements intact. We are as yet able in the case of very few elements to state with absolute certainty the average length of their life. But among all pathological new formations with fluid intercellular substance there is not a single one which is able to preserve its existence for any length of time—not a single one whose elements can become permanent constituents of the body, or exist as long as the individual. The tumour as a whole may last; but its individual elements perish. If we examine a tumour after it has existed for perhaps a year, we usually find that the elements first formed no longer exist in the centre; but that in the centre they are disintegrating, dissolved by fatty changes. If a tumour be seated on a surface, it often presents in the centre of its most prominent part a navel-like depression, and the parts under this display a dense cicatrix which no longer bears the original character of the new formation. Heterologous new formations must be considered parasitical in their nature, since every one of their elements will withdraw matters from the body which might be used for better purposes, and since even its first development implies the destruction of its parent structures.
In view of origin of new formations it were well to create a nomenclature showing their histological basis; but new names must not be introduced too suddenly, and it must be noted that there are certain tumours whose histological pedigree is still uncertain.
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