Disease and Its Causes by William Thomas Councilman

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As has been said, infection consists in the injury of the body by
living organisms which enter it. The body is in relation to the
external world by its surfaces only, and organisms must enter it by
some one of these surfaces. It is true that the bacteria in the
intestine--either those normally present or unusual varieties--may,
under certain circumstances, produce substances which are injurious
when absorbed; but this is not infection, and is analogous to any
other sort of poisoning. Each surface of the body has its own
bacterial flora. Organisms live on the surface either on matter which
is secreted by the surface or they use up an inappreciable amount of
body material. Many of these bacteria are harmless, some are
protective, producing by their growth such changes in the surface
fluids that these become hostile to the existence of other and
pathogenic forms. The surfaces also frequently harbor pathogenic
organisms which await some condition to arise which will permit them
to effect entrance into the tissues.

The surfaces of the body protect from invasion to a greater or less
degree. The skin protects by the impervious horny layer on the
outside, the external cells of which are dead and constantly being
thrown off. Bacteria are always found on and in this layer, but the
conditions for growth here are not very favorable and the surface is
constantly cleansed by desquamation. The new cells to supply the loss
are produced in the deepest layer of the epidermis, and the movement
of cells and fluids takes place from within outwards. The protection
is less perfect about the hairs and the sweat glands. Infection by the
route of the sweat glands is, however, uncommon, for the sweat is a
fluid unfavorable for bacterial growth and the flow acts mechanically
in washing away organisms which may have entered the ducts. Infection
by the route of the hair follicles is common. There is no mechanical
cleansing as by the sweat, the space around the hair is large and the
accumulated secretion of the hair glands and the desquamated cells
furnish a material in which bacteria may grow. Growing as a mass in
this situation, they may produce sufficient toxic material to destroy
adjacent living cells and thus effect entrance. Infection from the eye
is not common, the surface, though moist, is smooth; the eyelashes
around the margin of the lids give some mechanical protection from the
entrance of bacteria contained in dust, and the movements of the lids
and the constant and easily accelerated secretion of tears act
mechanically in removing foreign substances. It is possible that the
mechanical cleansing of the skin by the daily bath may have some
action in preventing infection.

The internal surfaces are much more exposed to attack and the
protection is not so efficient. The moisture of these surfaces is both
a protection and a source of danger. It protects by favoring the
lodgment near the orifices of organisms which are in the inspired air,
for when bacteria touch a moist surface they cannot be raised from
this and carried further by air currents. The moisture is a source of
danger in that it favors the growth of bacteria which lodge on the
surface. The respiratory surface which is most exposed to infection
from the air is further protected by the cilia, which are fine
hair-like processes covering the cells of the surface and which by
their constant motion sweep out fine particles of all sorts which
lodge upon them. The cavity of the mouth harbors large numbers of
organisms, many of them pathogenic. It forms a depot from which
bacteria may pass to communicating surfaces and infection from these
may result. Food particles collect in the mouth and provide culture
material, and there are many crypts and irregularities of surface
which oppose mechanical cleaning. Infection of the middle ear, the
most common cause of deafness, takes place by means of the Eustachian
tube which connects the cavity of the ear with the mouth. Organisms
from the mouth can extend into the various large salivary glands by
means of the ducts and give rise to infections. The tonsils,
particularly in children, provide a favorable surface for infection.
The mucous surface extends into these forming deep pockets lined with
very thin epithelium, and in these debris of all sorts accumulates and
provides material favorable for bacterial growth.

The lungs at first sight seem to offer the most favorable surface for
infection. The surface, ninety-seven square yards, is enormous; it is
moist, the epithelial covering is so thin as to give practically no
mechanical protection, large amounts of air constantly pass in and
out, and the surface is in contact with this. They are protected from
infection in many ways. The tubes or bronchi by which the air passes
into and from the lungs are covered with cilia; the surface area of
these tubes constantly enlarges as they branch, the sum of the
diameters of the small tubes being many times greater than that of the
windpipe, and this enlargement by retarding the motion of the air
favors the lodgment of particles on the surface whence they are
removed by the action of the cilia. The entering air is also brought
closely in contact with a moist surface at the narrow opening of the
larynx. That bacteria and other foreign substances can enter the lungs
in spite of these guards is shown not only by the infections which
take place here, but also by the large amount of black carbon
deposited in them from the soot contained in the air.

Infection rarely takes place from the surface of the gullet or
oesophagus which leads from the mouth to the stomach. This is due to
the smoothness of the surface and to the rapidity with which food
passes over it. Infection by the stomach also is rare, for this
contains a strong acid secretion which destroys many of the bacteria
which are taken in with the food. It is found impossible to infect
animals with cholera unless the acidity of the stomach contents be
neutralized by an alkali. Many organisms, although their growth in the
stomach is inhibited, are not destroyed there and pass into the
intestines, where the conditions for infection are more favorable.
This large and very irregular surface is bathed in fluid which is a
good culture medium and but a single layer of cells covers it. The
organisms which cause many of the infectious diseases in both man and
animals find entrance by means of the alimentary canal, as cholera,
dysentery, typhoid fever, chicken cholera, hog cholera.

Infection by the genito-urinary surface is comparatively rare. The
surface openings are usually closed, and the discharge of urine has a
mechanical cleansing effect. The wide tube of the vagina is further
protected by a normal bacterial flora which produces conditions
hostile to other and pathogenic bacteria. The most common infections
are the sexual diseases, which are due to organisms which find
favorable conditions for growth in and on the surface and which are
conveyed from a similar surface by sexual contact.

It remains a question whether bacteria can penetrate an intact surface
producing no injury at the point of entrance and be carried by the
lymph or blood into internal organs where they produce disease.
Internal infections are often found with seemingly intact body
surfaces, but it is impossible to exclude the presence of minute or
microscopic surface injuries by which the organisms may have entered.
It is also possible that a slight injury at the point of entrance may
heal so completely as to leave no trace.

The chief danger from wounds is that their surfaces may become
infected. Death from wounds is due more frequently to infection than
to the actual injury represented by the wounds. Much depends upon the
character of the wound. Infection of clean wounds which are made by a
sharp cutting instrument and from which there is abundant haemorrhage
with sealing of the edges of the wound by clotted blood, rarely
happens. Typical wounds of this sort are often made in shaving, and
infection of such wounds is extraordinarily rare. If, with the wound,
pathogenic organisms are placed in the tissue, or foreign substances
such as bits of clothing are carried in with a bullet, for example, or
if the instrument causing the wound be of such a character as to
produce extensive lacerations of tissue, infection is more apt to
occur. The less frequency of infection in modern wars is in part due
to the simpler character of the wounds and in part to the fact that
modern fixed ammunition is practically free from germs. The old
spear-head, the arrow, the cross bow bolt, had little regard for the
probabilities of infection. Whether infection follows a wound depends
both upon the entry of pathogenic organisms and upon these finding in
the tissues suitable opportunities for growth. In wounds in which
there is much laceration of tissue organisms find the most favorable
conditions for development. The very slight wounds produced by the
exploded cap in the toy pistol give suitable conditions for the
development of the bacillus which produces tetanus or lockjaw. The
deaths of children from lockjaw following a Fourth of July celebration
have often exceeded the total deaths in a Central American revolution.
The tetanus bacillus is a widely distributed organism, whose normal
habitat is in the soil and which is usually present on the dirty hands
of little boys. The toy-pistol wounds are made by small bits of paper
or metal being driven into the skin by the explosion of the cap. The
wound is of little moment, the surface becomes closed, and a bit of
foreign substance, a few dead cells and the tetanus bacilli from the
surface remain enclosed and in a few days the fatal disease develops.
Infection of the surfaces of old wounds such as the surface of an
ulcer takes place with difficulty. Large numbers of leucocytes which
give protection by phagocytosis are constantly passing to the surface,
and there is also a constant stream of fluid towards the surface. On
such a surface there may be an abundant growth of pathogenic
organisms, but no infection results.

In most infections there is a focus where the infectious organisms are
localized; this may correspond to the point of entrance on a surface
or it may be in the interior of the body, the organisms being
deposited there after entrance. At this primary localization, the
_atrium_ of infection,[1] the organisms multiply and from this
point further invasion takes place. Many secondary foci may be formed
in the organs by distribution of the organisms, or there may be
infection of the blood and fluids of the body. The injuries which are
produced depend upon the nature of the infecting organisms. The most
common lesion consists in the death of the tissue about the infecting
organisms. In most cases the sum of the changes are so characteristic
that from them the nature of the infection is easily determined, and
these changes often give names to the disease; thus tuberculosis is a
disease characterized by the formation of tubercles or little nodules
in the body. The situation of the foci of disease is determined by
many conditions, the most important being the varying resistance of
the different organs of the body to the growth of bacteria. Certain
organs, such as the central nervous system, the muscles, the testicles
and the ovaries, have a high resistance to the growth of bacteria. The
disease may be localized in certain organs because only in these do
the bacteria find favorable conditions for growth. In spite of a high
general resistance to infection the lesions in chronic glanders are
most marked in the muscles, those of poliomyelitis in the spinal cord.
There are few bacterial diseases which are localized in the blood, but
many of the diseases caused by protozoa have this localization. In
every infection some organisms enter the blood, which acts as a
carrier and deposits them in the organs.

Bacteria cause disease by producing substances called toxines which
are poisonous to the cells, and of which two sorts are distinguished.
One form of toxines is produced by the bacteria as a sort of
secretion, and is formed both in the body and when the bacteria are
growing in cultures. Substances of this character, many of them highly
poisonous, are produced both by animals and plants. They may serve the
purpose both of offence and defence, as in the case of the snake
venom, and in other cases they seem to benefit their producers in no
way whatever, and may even be injurious to them. After the different
cereals have been grown for succeeding years in the same place, growth
finally diminishes not from the exhaustion of the soil, but from the
accumulation in it of substances produced by the plants. Beneath
certain trees, as the Norway maple, grass will not grow, and it has
been shown that the tree produces substances which inhibit the growth
of grass. When bacteria are grown in a culture flask, growth ceases
long before the nutritive material has been consumed, from the
accumulation of waste products in the fluid. The other class of toxic
substances, called endotoxines, are not secretion products, but are
contained in the bacterial substance and become active by the
destruction and disintegration of the bacteria. They can be
artificially produced by grinding up masses of bacteria, and in the
body the destruction and solution of bacteria which is constantly
taking place sets them free. The toxines and the endotoxines are of an
albuminous nature, and act only when they come in contact with the
living cells within the body. When taken into the alimentary canal
they are either not absorbed or so changed by the digestive fluids as
to be innocuous. Many of the ordinary food substances, even a material
apparently so simple as the white of an egg, are highly injurious if
they reach the tissues in an unchanged form.

By means of these substances the bacteria produce such changes in
their environment within the body that this becomes adapted to their
parasitic existence. In symbiosis the bacteria probably undergo
changes by which they become adapted to the environment, and in
parasitism the environment becomes adapted to them. In the same way
man can change his immediate environment by means of clothing,
artificial heating, etc., and adapt it to his needs; or by hardening
his body he can adapt it to the environment. The pathogenic bacterium
finds the living tissue hostile, its cells devour him, the tissue
fluids destroy him, and by means of the toxines he changes the
environment from that of living to dead tissue, or in other ways so
alters it that it is no longer hostile. The parasite has also means of
passive defence comparable to the armor of the warrior in the past. It
may form a protective mantle called a capsule around itself, which
serves to protect it from the action of the body fluids. Such capsule
formation is a very common thing in the pathogenic organisms, and they
are found only when these are growing in the body and do not appear in
cultures (Fig. 17-c).

It is evident that just as the parasite has his weapons of offence and
defence so has the host, otherwise there would be no recovery from
infectious diseases. Although many of the infectious diseases have a
high mortality, which in rare instances reaches one hundred per cent,
the majority do recover. In certain cases the recovery is attended by
immunity, the individual being protected to a greater or less degree
from a recurrence of the same disease. The immunity is never absolute;
it may last for a number of years only, and usually, if the disease be
again acquired, the second attack is milder than the primary. Probably
the most enduring immunity is in smallpox, although cases are known of
two and even three attacks; the immunity is high in scarlet fever,
measles, mumps and typhoid fever. The immunity from diphtheria is
short, and in pneumonia, although there must be a temporary immunity,
future susceptibility to the disease is probably increased. In certain
cases the immunity is only local; the focus of disease heals because
the tissue there has evolved means of protection from the parasite,
but if any other part of the body be infected, the disease pursues the
usual course. A boil, for example, is frequently followed by the
appearance of similar boils in the vicinity due to the infection of
the skin by the micrococci from the first boil, which by dressings,
etc., have become spread over the surface.

The natural methods of defence of the host against the parasites have
formed the main subject in the study of the infectious diseases for
the last twenty years. Speculation in this territory has been rife and
most of it fruitless, but by patient study of disease in man and by
animal experimentation there has been gradually evolved a sum of
knowledge which has been applied in many cases to the treatment of
infectious diseases with immense benefit. Research was naturally
turned to this subject, for it was evident that the processes by which
the protection of the body was brought about must be known before
there could be a really rational method of treatment directed towards
the artificial induction of such processes, or hastening and
strengthening those which were taking place. Previous to knowledge of
the bacteria, their mode of life, their methods of infection and
knowledge of the defences of the body, most of the methods of
prevention and treatment of the infectious diseases was based largely
on conjecture, the one brilliant exception being the discovery of
vaccination by Jenner in 1798.

The host possesses the passive defences of the surfaces which have
already been considered. The first theories advanced in explanation of
immunity were influenced by what was known of fermentation. One, the
exhaustion theory, assumed that in the course of disease substances
contained in the body and necessary for the growth of the bacteria
became exhausted and the bacteria died in consequence. Another, the
theory of addition, assumed that in the course of the disease
substances inimical to the bacteria were formed. Both these theories
were inadequate and not in accord with what was known of the
physiology of the body. The most general mode of defence is by
phagocytosis, the property which many cells have of devouring and
digesting solid substances (Fig. 16-p). Although this had been known
to take place in the amoebae and other unicellular organisms, the wide
extent of the process and its importance in immunity was first
recognized by Metschnikoff in 1884 and the phagocytic theory of
immunity advanced and defended by a brilliant series of experiments by
Metschnikoff and his pupils conducted in the Pasteur Institute.
Metschnikoff's first observations were made on the daphnea, a small
animalcule just visible to the naked eye which lives in fresh water.
The structure of the organism is simple, consisting of an external and
internal surface between which there is a space, the body cavity;
daphneae are transparent and can be studied under the microscope while
living. Metschnikoff observed that certain of them in the aquarium
gradually lost their transparency and died, and examining these he
found they were attacked by a species of fungus having long, thin
spores. These spores were taken into the intestine with other food;
they penetrated the thin wall of the intestine, passed into the body
cavity, multiplied there, and in consequence the animal died. In many
cases, however, those penetrating became enclosed in cells which the
body cavity contains and which correspond with the leucocytes of the
blood; in these the spores were digested and destroyed. The daphneae in
which this took place recovered from the infection. Here was a case in
which all the stages of an infectious disease could be directly
followed under the microscope, and the whole process was simple in
comparison with infections in the higher animals. The pathogenic
organism was known, the manner and site of invasion was clear, it was
also evident that if the multiplication of the parasite was unchecked
the animal died, but if the parasite was opposed by the body cells and
destroyed the animal recovered. The studies were carried further into
the diseases of the higher animals, and it was found the leucocytes in
these played the same part as did the cells in the body cavity of the
daphnea. The introduction of bacteria into certain animals was
followed by their destruction within cells and no disease resulted; if
this did not take place, the bacteria multiplied and produced disease.
Support also was given the theory by the demonstration at about the
same time that in most of the infectious diseases the leucocytes of
the blood became increased in number,--that in pneumonia, for
instance, instead of the usual number of eight thousand in a cubic
millimeter of blood, there were often thirty thousand or even fifty
thousand. At about the same time also chemotaxis, or the action of
chemical substances in attracting or repelling organisms, excited
attention, and all these facts together became woven into the theory.
It was soon seen, however, that this theory, based as it was on
observation and supported by the facts observed, was not, at least in
its first crude form, capable of general application. Many animals
have natural immunity to certain diseases; they do not have the
disease under natural conditions, nor do they acquire the disease when
the organisms causing it are artificially introduced into their
tissues by inoculation. Such natural immunity seemed to be unconnected
with defence by phagocytosis, for the leucocytes of the animal might
or might not have phagocytic reaction to the particular organisms to
which the animal was immune. It was also seen that recovery from
infection in certain diseases was unconnected with phagocytosis. It
had also been demonstrated, by German observers chiefly, that the
serum of the blood, the colorless fluid in which the corpuscles float,
was itself destructive, and that in an animal rendered immune to a
special bacterium the destructive action of the serum on that organism
was greatly increased. In this hostile serum the bacteria often became
clumped together in masses, the bodies became swollen, broken up, and
finally disintegrated. This property of the serum was described as due
to a substance in the serum called _alexine_, which in the immune
animal became greatly increased in amount. It was even denied by some
that phagocytosis of living bacteria took place, and that all those
included in the cells were dead, having been destroyed in the first
instance by the serum. The strife became a national one between the
French and Germans,--on the one side in France the phagocytic theory
was defended, and in Germany, on the other, the theory of serum
immunity. The mass of experimental work which poured from the
laboratories of the two countries in attack and defence became so
great that it could not easily be followed. It had a good influence
because, without the stimulation of this national rivalry, the
knowledge which gradually arose from this work would not have been so
quickly acquired. It is interesting that the mode of action of the
serum in destroying bacteria was demonstrated not by a German but by
Bordet, a French observer and a pupil of Metschnikoff. He showed that
the serum contained two distinct substances, each necessary for the
destructive action. The separate action of these substances can be
studied since one is _thermolabile_, or destroyed by heating the
serum to one hundred and thirty-three degrees; the other
_thermostabile_, or capable of withstanding a greater degree of
heat. These substances are known only by their effect, they have never
been separated from the serum. The thermostabile substance, or
_amboceptor_, as it is generally called, has in itself no
destructive action on the bacteria; but in some way so alters them
that they can be acted on by the thermolabile substance called
_complement_ whose action is destructive. The amount of
amboceptor may increase in the course of infection and its formation
stimulated, the amount of complement remains unchanged. The action of
the amboceptor is specific, that is, directed against a single species
of bacterium only; the destructive power of the blood may be very
great against a single bacterium species and have no effect on others.
There seem naturally to be many different amboceptors in the blood,
and the number may be very greatly increased. It has been shown as a
result of the work of many investigators that the shield has two
faces,--there is destruction both by cells and fluids and there is
interaction by both. The amboceptors so necessary for the destructive
action of the serum are produced by the body cells, particularly the
leucocytes. The serum assists in pagocytosis by the action on bacteria
of substances called _opsonins_ which are contained in it, and
the formation of which can be very greatly stimulated. Again, not all
inclusion of bacteria within leucocytes is indicative of phagocytosis;
in many cases the bacteria seem to find the best conditions for
existence within the leucocytes, and these and not the bacteria are
destroyed.

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