[*] Paper delivered before the Virginia Medical Association,
Washington, D. C., October 29, 1914.
Alkalis and bases compose the greater part of the food of man
and animals, the blood in both man and animals under normal conditions
being slightly alkaline or rather potentially alkaline; that is,
although in circulating blood the concentration of the OH-ions--
upon which the degree of alkalinity depends--is but little more
than in distilled water, yet blood has the power of neutralizing
a considerable amount of acid (Starling, Wells). At the time of death,
whatever its cause, the concentration of H-ions in the blood increases,--
the concentration of H-ions being a measure of acidity,--that is,
the potential or actual alkalinity decreases and the blood becomes
actually neutral or acid.
To determine what conditions tend to diminish the normal alkalinity
of the blood, many observations were made for me in my laboratory
by Dr. M. L. Menten to determine by electric measurements
the H-ion concentration of the blood under certain pathologic
and physiologic conditions.
As a result of these researches we are able to state that the H-ion
concentration of the blood--its acidity--is increased by excessive
muscular activity; excessive emotional excitation; surgical shock;
in the late stages of infection; by asphyxia; by strychnin convulsions;
by inhalation anesthetics; after excision of the pancreas, and in the late
stages of life after excision of the liver and excision of the adrenals.
Morphin and decapitation cause no change in the H-ion concentration.
Ether, nitrous oxid, and alcohol produce an increased acidity
of the blood which is proportional to the depth of anesthesia.
Many of the cases studied were near death, as would be expected,
since it is well known that a certain degree of acidity is
incompatible with life.
Since alkalis and bases preponderate in ingested food;
since alkalinity of the blood is diminished by bodily activity;
and since at the point of death the blood is always acid, we may
infer that some mechanism or mechanisms of the body were evolved
for the purpose of changing bases into acids that thus energy
might be liberated.
These observations lead naturally to the question, May not
acidity of itself be the actual final cause of death?
We believe that it may be so from the facts that--(1)
The intravenous injection of certain acids causes death quickly,
but that convulsions do not occur, since the voluntary muscles
lose their power of contraction; and (2) the intravenous injection
of acids causes extensive histologic changes in the brain,
the adrenals, and the liver which resemble the changes invariably
caused by activation of the kinetic system (Figs. 74 and 75). In view
of these facts may we not find that anesthesia and many instances
of unconsciousness are merely phenomena of acidity?
As has been stated already, we have found that the H-ion concentration
of the blood--its acidity--is increased by alcohol, by ether,
and by nitrous oxid. In addition our tests have shown that under
ether the increase of the H-ion concentration--acidity--is more
gradual than under nitrous oxid, an observation which accords well
with the fact that nitrous oxid more quickly induces anesthesia
than does ether.
Further striking testimony in favor of the hypothesis that
the production of acidity by inhalation anesthetics is the method
by which anesthesia itself is produced is found in the fact
that although lethal doses of acid cause muscular paralysis,
yet this paralysis may be mitigated by adrenalin--which is alkaline.
This observation may explain in part the remarkable success of
the method of resuscitation devised by me, in which animals "killed"
by anesthetics and asphyxia are revived by the use of adrenalin.
In animals under inhalation anesthesia Williams found that no
nerve-current could be detected by the Einthoven string galvanometer,
a fact which might be explained by postulating that nerve-currents
can flow from the brain to the muscles and glands only when there
is a difference of potential. Any variation from the normal
alkalinity of the body must change the difference in potential.
Since the nerve-currents in animals under anesthesia are not demonstrable
by any apparatus at our command, and since anesthesia produces acidity,
then we may infer that acidity reduces the difference in potential.
As long as there is life, a galvanometer of sufficient delicacy
would perforce detect, a nerve-current until the acidity increased
to such a point as to reduce the difference in potential to zero--
the point of death. If at this point a suitable alkali--
adrenalin solution--can be introduced quickly enough, the vital difference
in potential may be restored and the life processes will be renewed.
Bearing especially on this point is the fact that if adrenalin
in sufficient quantities be administered simultaneously with an acid,
it will not only prevent the fall in blood-pressure usually
caused by the acid, but will also prevent the histologic changes
in the brain, adrenals, and liver which are usually caused by
the intravenous injection of acids.
This hypothesis regarding the cause of anesthesia and unconsciousness
explains and harmonizes many facts. It explains how asphyxia,
overwhelming emotion, and excessive muscular exertion, by causing acidity,
may produce unconsciousness. It explains the acidosis which results
from starvation, from uremia, from diabetes, from Bright's disease,
and supplies a reason for the use of intravenous infusions of sodium
bicarbonate to overcome the coma of diabetes and uremia (Fig. 76).
It may explain the quick death from chloroform and nitrous oxid;
and may perhaps show why unconsciousness is so commonly the immediate
precursor of death.
One of the most noticeable immediate effects of the administration
of an inhalation anesthetic is a marked increase in the rapidity
and force of the respiration. The respiratory center has evidently
been evolved to act with an increase of vigor which is proportional--
within certain limits--to the increase in the H-ion concentration,
whereas the centers governing the voluntary muscles are inhibited.
In this antithetic reaction of the higher cortical centers and the lower
centers in the medulla to acidity we find a remarkable adaptation
which prevents the animal from killing itself by the further increase
in acidity which would be produced by muscular activity. That is,
as the acidity produced by muscular action increases and threatens life,
the respiratory action, by which carbon dioxid is eliminated and
oxygen supplied, is increased, while the driving power of the brain,
which produces acidity, is diminished or even inhibited entirely;
that is, the state of unconsciousness or anesthesia is reached.
We conclude first that, without this life-saving regulation,
animals under stress would inevitably commit suicide; and, second,
that it is probable that the remarkable phenomenon of anesthesia--
the coincident existence of unconsciousness and life--is due to this
antithetic action of the cortex and the medulla.
In the human, as in the animal, the degree of acidity parallels
the depth of inhalation anesthesia.
Within a few seconds after beginning nitrous oxid anesthesia the acidity
of the blood is increased. This rapid acidulation is synchronous
with almost instantaneous unconsciousness and increased respiration.
If the oxygen in the inhaled mixture be increased, a decrease in
acidity is again synchronous with lighter anesthesia and a decrease
in the respiratory rate.
If these premises be sound, we are justified in asserting that the state
of anesthesia is due to an induced acidity of the blood. If the acidity
is slight, then the anesthesia is slight and the force of the nerve
impulses is lessened, but the patient is still conscious of them.
As the acidity increases associative memory is lost, and the patient
is said to be unconscious: the centers governing the voluntary muscles
are not inhibited, however, and cutting the skin causes movements.
If the acidity is further increased, there is loss of muscular tone
and even the strong contact ceptor stimuli of a surgical operation
do not cause any muscular response, and, finally, the acidity may be
increased to the point at which the respiratory and circulatory centers
can no longer respond by increased effort, and anesthetic death--
that is, ACID death--follows.
Certain clinical phenomena are clarified by this theory and serve
to substantiate it. For example, it is well known that inhalation
anesthesia precipitates the impending acidosis which results
from starvation, from extreme Graves' disease, from great exhaustion,
from surgical shock, and from hemorrhage, and which is present
when death from any cause is imminent.
We see, therefore, that anesthesia is made possible, first, by the fact
that inhalation anesthetics cause acidity, and, second, by the antithetic
adaptation of the higher centers in the brain and of the centers
governing respiration and circulation.
In deep contrast to the action of inhalation anesthetics is that
of narcotics. Deep narcotization with morphin and scopolamin is
induced slowly; the respiratory and pulse-rate are progressively lessened--
and there is no acidity.
By our researches we have established in what consists the generic
difference between inhalation anesthetics and narcotics.
In our experiments no increase in the H-ion concentration was produced
by morphin or by scopolamin, no matter how deep the narcotization.
In animals already narcotized by morphin the production of acid by any
of the acid-producing stimuli was delayed or prevented. On the other hand,
in animals in which an acidity had already been produced by ether,
by shock, by anger, or by fear, the later administration of morphin
delayed or inhibited entirely the neutralization of the acidity.
In other words, morphin interferes with the normal mechanism by
which acidity is neutralized possibly because its inhibiting action
on the respiratory center is sufficient to overcome the stimulating
action of acidity on that center, for, as we have stated,
the neutralization of acidity is in large measure accomplished
by the increased respiration induced by the acidity itself.