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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