Disease and Its Causes by William Thomas Councilman

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FOOTNOTES:
[1] By cachexia is understood a condition of malnutrition and
emaciation which is usually accompanied by a pale sallow color of the
skin.

[2] By trauma is understood a wound or injury of any sort.

CHAPTER IV

THE REACTIONS OF THE TISSUES OF THE BODY TO INJURIES.--INFLAMMATION.--
THE CHANGES IN THE BLOOD IN THIS.--THE EMIGRATION OF THE CORPUSCLES OF
THE BLOOD.--THE EVIDENT CHANGES IN THE INJURED PART AND THE MANNER IN
WHICH THESE ARE PRODUCED.--HEAT, REDNESS, SWELLING AND PAIN.--THE
PRODUCTION OF BLISTERS BY SUNBURN.--THE CHANGES IN THE CELLS OF AN
INJURED PART.--THE CELLS WHICH MIGRATE FROM THE BLOOD-VESSELS ACT AS
PHAGOCYTES.--THE MACROPHAGES.--THE MICROPHAGES.--CHEMOTROPISM.--THE
HEALING OF INFLAMMATION.--THE REMOVAL OF THE CAUSE.--CELL REPAIR AND
NEW FORMATION.--NEW FORMATION OF BLOOD-VESSELS.--ACUTE AND CHRONIC
INFLAMMATION.--THE APPARENTLY PURPOSEFUL CHARACTER OF THE CHANGES IN
INFLAMMATION.

Injury and repair have already been briefly considered in their
relation to the normal body and to old age; there are, however,
certain phenomena included under the term inflammation which follow
the more extensive injuries and demand a closer consideration than was
given in Chapter II. These phenomena differ in degree and character;
they are affected by the nature of the injurious agent and the
intensity of its action, by the character of the tissue which is
affected and by variations in individual resistance to injury. A blow
which would have no effect upon the general surface of the body may
produce serious results if it fall upon the eye, and less serious
results for a robust than for a weak individual.

Most of the changes which take place after an injury and their
sequence can be followed under the microscope. If the thin membrane
between the toes of a living frog be placed under the microscope the
blood vessels and the circulating blood can be distinctly seen in the
thin tissue between the transparent surfaces. The arteries, the
capillaries and veins can be distinguished, the arteries by the
changing rapidity of the blood stream within them, there being a
quickening of the flow corresponding with each contraction of the
heart; the veins appear as large vessels in which the blood flows
regularly (Fig. 11). Between the veins and arteries is a large number
of capillaries with thin transparent walls and a diameter no greater
than that of the single blood corpuscles; they receive the blood from
the arteries and the flow in them is continuous. The white and red
blood corpuscles can be distinguished, the red appearing as oval discs
and the white as colorless spheres. In the arteries and veins the red
corpuscles remain in the centre of the vessels appearing as a rapidly
moving red core, and between this core and the wall of the vessels is
a layer of clear fluid in which the white corpuscles move more slowly,
often turning over and over as a ball rolls along the table.

If, now, the web be injured by pricking it or placing some irritating
substance upon it, a change takes place in the circulation. The
arteries and the veins become dilated and the flow of blood more
rapid, so rapid, indeed, that it is difficult to distinguish the
single corpuscles. In a short while the rapidity of flow in the
dilated vessels diminishes, becoming slower than the normal, and the
separation between the red and white corpuscles is not so evident. In
the slowly moving stream the white corpuscles move much more slowly
than do the red, and hence accumulate in the vessels lining the inner
surface and later become attached to this and cease to move forward.
The attached corpuscles then begin to move as does an amoeba, sending
out projections, some one of which penetrates the wall, and following
this the corpuscles creep through. Red corpuscles also pass out of the
vessels, this taking place in the capillaries; the white corpuscles,
on the other hand, pass through the small veins. Not only do the white
corpuscles pass through the vessels, but the blood fluid also passes
out. The corpuscles which have passed into the tissue around the
vessels are carried away by the outstreaming fluid, and the web
becomes swollen from the increased amount of fluid which it contains.
The injured area of the web is more sensitive than a corresponding
uninjured area and the foot is more quickly moved if it be touched. If
the injury has been very slight, observation of the area on the
following day will show no change beyond a slight dilatation of the
vessels and a great accumulation of cells in the tissue.

Everyone has experienced the effect of such changes as have been
described in this simple experiment. An inflamed part on the surface
of the body is redder than the normal, swollen, hot and painful. The
usual red tinge of the skin is due to the red blood contained in the
vessels, and the color is intensified when, owing to the dilatation,
the vessels contain more blood. The inflamed area feels hot, and if
the temperature be taken it may be two or three degrees warmer than a
corresponding area. The increased heat is due to the richer
circulation. Heat is produced in the interior of the body chiefly in
the muscles and great glands, and the increased afflux of blood brings
more heat to the surface. A certain degree of swelling of the tissue
is due to the dilatation of the vessels; but this is a negligible
factor as compared with the effect of the presence of the fluid and
cells of the exudate.[1] The fluid distends the tissue spaces, and it
may pass from the tissue and accumulate on surfaces or in the large
cavities within the body. The greatly increased discharge from the
nose in a "cold in the head" is due to the exudation formed in the
acutely inflamed tissue, and which readily passes through the thin
epithelial covering. Various degrees of inflammation of the skin may
be produced by the action of the sun, the injury being due not to the
heat but to the actinic rays. In a mild degree of exposure only
redness and a strong sense of heat are produced, but in prolonged
exposure an exudate is formed which causes the skin to swell and
blisters to form, these being due to the exudate which passes through
the lower layers of the cells of the epidermis and collects beneath
the impervious upper layer, detaching this from its connections. If a
small wad of cotton, soaked in strong ammonia, be placed on the skin
and covered with a thimble and removed after two minutes, minute
blisters of exudate slowly form at the spot.

The pain in an inflamed part is due to a number of factors, but
chiefly to the increased pressure upon the sensory nerves caused by
the exudate. The pain varies so greatly in degree and character that
parts which ordinarily have little sensation may become exquisitely
painful when inflamed. The pain is usually greater when the affected
part is dense and unyielding, as the membranes around bones and teeth.
The pain is often intermittent, there being acute paroxysms
synchronous with the pulse, this being due to momentary increase of
pressure when more blood is forced into the part at each contraction
of the heart. The pain may also be due to the direct action of an
injurious substance upon the sensory nerves, as in the case of the
sting of an insect where the pain is immediate and most intense before
the exudate has begun to appear.

When an inflamed area is examined, after twenty-four hours, by
hardening the tissue in some of the fluids used for this purpose and
cutting it into very thin slices by means of an instrument called a
microtome, the microscope shows a series of changes which were not
apparent on naked eye examination. The texture is looser, due to the
exudate which has dilated all the spaces in the tissue. Red and white
corpuscles in varying numbers and proportions infiltrate the tissue;
all the cells which belong to the part, even those forming the walls
of the vessels, are swollen, the nuclei contain more chromatin, and
the changes in the nuclei which indicate that the cells are
multiplying appear. The blood vessels are dilated, and the part in
every way gives the indication of a more active life within it. There
are also evidences of the tissue injury which has called forth all the
changes which we have considered. (Fig. 15.)

[Illustration: FIG. 15--A SECTION OF AN INFLAMED LUNG SHOWING THE
EXUDATE WITHIN THE AIR SPACES. Compare this with Fig 6. Fig 15 is from
the human lung, in which the air spaces are much larger than in the
mouse.]

The microscopic examination of any normal tissue of the body shows
within it a variable number of cells which have no intimate
association with the structure of the part and do not seem to
participate in its function. They are found in situations which
indicate that these cells have power of active independent motion. In
the inflamed tissue a greatly increased number of these cells is
found, but they do not appear until the height of the process has
passed, usually not before thirty-six or forty-eight hours after the
injury has been received. The numbers present depend much upon the
character of the agent which has produced the injury, and they may be
more numerous than the ordinary leucocytes which migrate from the
blood vessels.

All these changes which an injured part undergoes are found when
closely analyzed to be purposeful; that is, they are in accord with
the conditions under which the living matter acts, and they seem to
facilitate the operation of these conditions. It has been said that
the life of the organism depends upon the cooerdinated activity of the
living units or cells of which it is composed. The cells receive from
the blood material for the purpose of function, for cell repair and
renewal, and the products of waste must be removed. In the injury
which has been produced in the tissue all the cells have suffered,
some possibly displaced from their connections, others may have been
completely destroyed, others have sustained varying degrees of injury.
If the injury be of an infectious character, that is, produced by
bacteria, these may be present in the part and continue to exert
injury by the poisonous substances which they produce, or if the
injury has been produced by the action of some other sort of poison,
this may be present in concentrated form, or the injury may have been
the result of the presence of a foreign body in the part. Under these
conditions, since the usual activities of the cells in the injured
part will not suffice to restore the integrity of the tissue, repair
and cell formation must be more active than usual, any injurious
substances must be removed or such changes must take place in the
tissue that the cell life adapts itself to new conditions.

[Illustration: FIG. 16.--PHAGOCYTOSIS. _a_, _b_, _c_ are the
microphages or the bacterial phagocytes. (_a_) Contains a number of
round bacteria, and (_b_) similar bacteria arranged in chains, and
(_c_) a number of rod-shaped bacteria (_d_) Is a cell phagocyte or
macrophage which contains five red blood corpuscles.]

All life in the tissues depends upon the circulation of the blood.
There is definite relation between the activity of cells and the blood
supply; a part, for instance, which is in active function receives a
greater supply of blood by means of dilatation of the arteries which
supply it. If the body be exactly balanced longitudinally on a
platform, reading or any exercise of the brain causes the head end to
sink owing to the relatively greater amount of blood which the brain
receives when in active function. The regulation of the blood supply
is effected by means of nerves which act upon the muscular walls of
the arteries causing, by the contraction or the relaxation of the
muscle, diminution or dilatation of the calibre of the vessel. After
injury the dilatation of the vessels with the greater afflux of blood
to the part is the effect of the greatly increased cell activity, and
is a necessity for this. In many forms of disease it has been found
that by increasing the blood flow to a part and producing an active
circulation in it, that recovery more readily takes place and many of
the procedures which have been found useful in inflammation, such as
hot applications, act by increasing the blood flow. So intimate is the
association between cell activity, as shown in repair and new
formation of cells, and the blood flow, that new blood vessels
frequently develop by means of which the capacity for nutrition is
still more increased. The cornea or transparent part of the eye
contains no blood vessels, the cells which it contains being nourished
by the tissue fluid which comes from the outside and circulates in
small communicating spaces. If the centre of the cornea be injured,
the cells of the blood vessels in the tissue around the cornea
multiply and form new vessels which grow into the cornea and appear as
a pink fringe around the periphery; when repair has taken place the
newly formed vessels disappear.

The exudate from the blood vessels in various ways assists in repair.
An injurious substance in the tissue may be so diluted by the fluid
that its action is minimized. A small crystal of salt is irritating to
the eye, but a much greater amount of the same substance in dilute
solution causes no irritation. The poisonous substances produced by
bacteria are diluted and washed away from the part by the exudate. Not
only is there a greater amount of tissue fluid in the inflamed part,
but the circulation of this is also increased, as is shown by
comparing the outflow in the lymphatic vessels with the normal. The
fluid exudate which has come from the blood and differs but slightly
from the blood fluid exerts not only the purely physical action of
removing and diluting injurious substances, but in many cases has a
remarkable power, exercised particularly on bacterial poisons, of
neutralizing poisons or so changing their character that they cease to
be injurious.

We have learned, chiefly from the work of Metschnikoff, that those
white corpuscles or leucocytes which migrate from the vessels in the
greatest numbers have marked phagocytic properties, that is, they can
devour other living things and thus destroy them just as do the
amoebae. In inflammations produced by bacteria there is a very active
migration of these cells from the vessels; they accumulate in the
tissue and devour the bacteria. They may be present in such masses as
to form a dense wall around the bacteria, thus acting as a physical
bar to their further extension. The other form of amoeboid cell, which
Metschnikoff calls the macrophage, has more feeble phagocytic action
towards bacteria, and these are rarely found enclosed within them. It
is chiefly by means of their activity that other sorts of substances
are removed. They often contain dead cells or cell fragments, and when
haemorrhage takes place in a tissue they enclose and remove the
granules of blood pigment which result. They often join together,
forming connected masses, and surround such a foreign body as a hair,
or a thread which the surgeon places in a wound to close it. They may
destroy living cells, and do this seemingly when certain cells are in
too great numbers and superfluous in a part, their action tending to
restore the cell equilibrium. The foreign cells do even more than
this: they themselves may be devoured by the growing cells of the
tissue, seemingly being actuated by the same supreme idea of sacrifice
which led Buddha to give himself to the tigress.

The explanation of most of the changes which take place in
inflammation is obvious. It is a definite property of all living
things that repair takes place after injury, and certain of the
changes are only an accentuation of those which take place in the
usual life; but others, such as the formation of the exudate, are
unusual; not only is the outpouring of fluid greatly increased, but
its character is changed. In the normal transudation[2] the substances
on which the coagulation of the blood depends pass through the vessel
wall to a very slight extent, but the exudate may contain the
coagulable material in such amounts that it easily clots. The
interchange between the fluid outside the vessels and the blood fluid
takes place by means of filtration and osmosis. There is a greater
pressure in the vessels than in the fluid outside of them, and the
fluid filters through the wall as fluid filters through a thin
membrane outside of the body. Osmosis takes place when two fluids of
different osmotic pressure are separated by animal membrane.
Difference in osmotic pressure is due to differences in molecular
concentration, the greater the number of molecules the greater is the
pressure, and the greater rapidity of flow is from the fluid of less
pressure to the fluid of greater pressure. The molecular concentration
of tissue and blood fluid is constantly being equalized by the process
of osmosis. In the injured tissue the conditions are more favorable
for the fluid of the blood to pass from the vessels: by filtration,
because owing to the dilatation of the arteries there is increased
amount of blood and greater pressure within the vessels, and the
filtering membrane is also thinner because the same amount of membrane
(here the wall of the vessel) must cover the larger surface produced
by the dilatation. It is, moreover, very generally believed that there
are minute openings in the walls of the capillaries, and these would
become larger in the dilated vessel just as openings in a sheet of
rubber become larger when this is stretched. Osmosis towards the
tissue is favored because, owing to destructive processes the
molecular pressure in the injured area is increased; an injured tissue
has been shown to take up fluid more readily outside of the body than
a corresponding uninjured tissue. The slowing of the blood stream, in
spite of the dilatation of the vessels, is due to the greater friction
of the suspended corpuscles on the walls of the vessels. This is due
to the loss from the blood of the outstreaming fluid and the relative
increase in the number of corpuscles, added to by the unevenness of
surface which the attached corpuscles produce.

The wonderful migration of the leucocytes, which seems to show a
conscious protective action on their part, takes place under the
action of conditions which influence the movement of cells. When an
actively moving amoeba is observed it is seen that the motion is not
the result of chance, for it is influenced by conditions external to
the organism; certain substances are found to attract the amoebae
towards them and other substances to repel them. These influences or
forces affecting the movements of organisms are known as
_tropisms_, and play a large part in nature; the attraction of
various organisms towards a source of light is known as
_heliotropism_, and there are many other instances of such
attraction. The leucocytes as free moving cells also come under the
influence of such tropisms. When a small capillary tube having one end
sealed is partially filled with the bacteria which produce abscess and
placed beneath the skin it quickly becomes filled with leucocytes,
these being attracted by the bacteria it contains. Dead cells exert a
similar attraction for the large phagocytes. Such attraction is called
_chemotropism_ and is supposed to be due in the cases mentioned,
to the action of chemical substances such as are given off by the
bacteria or the dead cells. The direction of motion is due to
stimulation of that part of the body of the leucocyte which is towards
the source of the stimulus. The presence in the injured part of
bacteria or of injured and dead cells exerts an attraction for the
leucocytes within the vessels causing their migration. When the centre
of the cornea is injured, this tissue having no vessels, all the
vascular phenomena take place in the white part of the eye immediately
around the cornea, this becoming red and congested. The migration of
leucocytes from the vessels takes place chiefly on the side towards
the cornea, and the migrated cells make their way along the devious
tracts of the communicating lymph spaces to the area of injury. The
objection may be raised that it is difficult to think of a chemical
substance produced in an injured area no larger than a millimeter,
diffusing through the cornea and reaching the vessels outside this in
such quantity and concentration as to affect their contents, nor has
there been any evidence presented that definite chemical substances
are produced in injured tissues; but there is no difficulty in view of
the possibilities. It is not necessary to assume that an actual
substance so diffuses itself, but the influence exerted may be thought
of as a force, possibly some form of molecular motion, which is set in
action at the area of injury and extends from this. No actual
substance passes along a nerve when it conveys an impulse.

We have left the injured area with an increased amount of fluid and
cells within it, with the blood vessels dilated and with both cells
and fluid streaming through their walls, and the cells belonging to
the area actively repairing damages and multiplying. The process will
continue as long as the cause which produces the injury continues to
act, and will gradually cease with the discontinuance of this action,
and this may be brought about in various ways. A foreign body may be
mechanically removed, as when a thorn is plucked out; or bacteria may
be destroyed by the leucocytes; or a poison, such as the sting of an
insect, may be diluted by the exudate until it be no longer injurious,
or it may be neutralized. Even without the removal of the cause the
power of adaptation will enable the life of the affected part to go
on, less perfectly perhaps, in the new environment. The excess of
fluid is removed by the outflow exceeding the inflow, or it may pass
to some one of the surfaces of the body, or in other cases an incision
favors its escape. The excess of cells is in part removed with the
fluid, in part they disappear by undergoing solution and in part they
are devoured by other cells. With the diminishing cell activity the
blood vessels resume their usual calibre, and when the newly formed
vessels become redundant they disappear by undergoing atrophy in the
same way as other tissues which have become useless.

When these changes take place rapidly the inflammation is said to be
acute, and chronic when they take place slowly. Chronic inflammation
is more complex than is the acute, and there is more variation in the
single conditions. The chronicity may be due to a number of
conditions, as the persistence of a cause, or to incompleteness of
repair which renders the part once affected more vulnerable, to such a
degree even that the ordinary conditions to which it is subjected
become injurious. A chronic inflammation may be little more than an
almost continuous series of acute inflammations, with repair
continuously less perfect. Chronic imflammations are a prerogative of
the old as compared with the young, of the weak rather than the
strong.

FOOTNOTES:
[1] The term exudation is used to designate the
passing of cells and fluid from the vessels in inflammation; the
material is the exudate.

[2] By transudation is meant the constant interchange between
the blood and the tissue fluid.

CHAPTER V

INFECTIOUS DISEASES.--THE HISTORICAL IMPORTANCE OF EPIDEMICS OF
DISEASE.--THE LOSSES IN BATTLE CONTRASTED WITH THE LOSSES IN ARMIES
PRODUCED BY--INFECTIOUS DISEASES.--THE DEVELOPMENT OF KNOWLEDGE OF
EPIDEMICS.--THE VIEWS OF HIPPOCRATES AND ARISTOTLE.--SPORADIC AND
EPIDEMIC DISEASES.--THE THEORY OF THE EPIDEMIC CONSTITUTION.--THEORY
THAT THE CONTAGIOUS MATERIAL IS LIVING.--THE DISCOVERY OF BACTERIA BY
LOEWENHOECK IN 1675.--THE RELATION OF CONTAGION TO THE THEORY OF
SPONTANEOUS GENERATION.--NEEDHAM AND SPALLANZANI.--THE DISCOVERY OF
THE COMPOUND MICROSCOPE IN 1605.--THE PROOF THAT A LIVING ORGANISM IS
THE CAUSE OF A DISEASE.--ANTHRAX.--THE DISCOVERY OF THE ANTHRAX
BACILLUS IN 1851.--THE CULTIVATION OF THE BACILLUS BY KOCH.--THE MODE
OF INFECTION.--THE WORK OF PASTEUR ON ANTHRAX.--THE IMPORTANCE OF THE
DISEASE.

These are diseases which are caused by living things which enter the
tissues of the body and, living at the expense of the body, produce
injury. Such diseases play an important part in the life of man; the
majority of deaths are caused directly or indirectly by infection. No
other diseases have been so much studied, and in no other department
of science has knowledge been capable of such direct application in
promoting the health, the efficiency and the happiness of man. This
knowledge has added years to the average length of life, it has
rendered possible such great engineering works as the Panama Canal,
and has contributed to the food supply by making habitation possible
over large and productive regions of the earth, formerly uninhabitable
owing to the prevalence of disease. It is not too much to say that our
modern civilization is dependent upon this knowledge. The massing of
the people in large cities, the factory life, the much greater social
life, which are all prominent features of modern civilization, would
be difficult or impossible without control of the infectious diseases.
The rapidity of communication and the increased general movement of
people, which have developed in equal ratio with the massing, would
serve to extend widely every local outbreak of infection. The
principles underlying fermentation and putrefaction which have been
applied with great economic advantage to the preservation of food were
many of them developed in the course of the study of the infectious
diseases. Whether the development of the present civilization is for
the ultimate advantage of man may perhaps be disputed, but medicine
has made it possible.

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