Carbonic acid in medicine

Front matter

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Atonia Gastrica

By ACHILLES ROSE, M.D., and ROBERT COLEMAN KEMP, M.D.

Preface

Among the transactions of the Congress of Balneologists which met in Berlin from March 9 to March 13, 1905, perhaps the most important were the papers read by Homberger and Fellner on the effect of carbonic-acid baths. These two papers are certainly the best which have been written on the physiological action of carbonic acid externally applied. They present investigations of Winternitz, Fellner, Homberger, and others, which furnish a scientific basis for a number of facts, thus far only empirical. These publications, of which I have availed myself, reached me just in time before I placed the manuscript of this book in the hands of the typographer.

The history of carbonic acid in medicine is very little known. At least, text-books hardly speak of it. The material for the historical sketch here given I found in great part in French and German books not translated into English. Among these was Lavoisier, " Me-

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PREFACE

thode de nomenclature chimique. Memoire sur la necessite de reformer la nomenclature de la chimie," lu a I'Assemble publique de TAcademie Royale des Sciences du i8 Avril 1787. This precious and probably rare book I found in the New York Academy of Medicine. It had formerly belonged to the library of the New York Hospital. Some of my readers will be pleased to have their attention called to it.

In writing the chapter on the Physiology and Chemistry of Respiration I availed myself of Hammarsten, " Lehrbuch der physiologischen Chemie." Several chapters are to some extent a reproduction of papers published by me during the last twenty-two years. The observations on the value of carbonic acid in dysentery, rhinitis, vomiting in pregnancy, and the solution of the problem of curing rectal fistula without operation I am confident will be confirmed in time, in spite of misocainia, with which we have to reckon when presenting a new subject.

I desire to express my gratitude first of all to Dr. E. C. Dent, the Medical Superintendent of Manhattan State Hospital, Wards Island,

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PREFACE

for his courtesy in permitting me to introduce carbonic- acid-gas baths in his institution, and to the members of the staff of Manhattan State Hospital, among these especially my friend Dr. R. C. Kemp. They all aided me generously in my investigations. I wish to express my thanks also to my colleagues of the New York Post-Graduate Medical School : Drs. Thomas E. Satterthwaite, Duncan Macpherson, and Frank Newton Irwin, who took an active interest in my modest labors.

Friends have asked me how I came to devote myself to the study of carbonic acid. This question always brought to my mind an anamnesis : the memory of my dear old friend Mr. Thomas Warker who early excited my interest in it. During the last decades of his life he had been industrious and indefatigable in inventing contrivances for the application of carbonic acid. His personal relations to Demarquay had inspired him with enthusiastic faith in the future of carbonic acid in medicine.

A. Rose.

New York, August 20, 1905.

Contents

CHAP. PAGE

Preface v

I. The Physiology and Chemistry of Respiration, i

Chapter I The Physiology And Chemistry Of Respiration

Carbonic acid is a constant constituent of the animal organism, the minor portion being supplied by the atmosphere. Absorption of carbonic acid from the atmosphere is partly due to the respiratory function of the skin. Abernethy (1764-1831) already had demonstrated that the skin is a vast respiratory surface; it is true it can not be compared with the lungs, but it is nevertheless very efficient. Abernethy's experiments to find the degree of absorption of different gases by the Skin show that, after oxygen, carbonic acid is the most absorbable.

Carbonic acid is taken up also through nutrition, but the larger part is derived from the tissues and the blood, and forms one of the

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most important end-products of oxidation and tissue metamorphosis. It develops the effects of a weak acid as well as those of an excitant and paralyzing agent, similar to alcohol. It enters the blood in the capillary circulation from the tissues in which it is formed.

The gases occurring in the blood under ordinary physiological conditions are oxygen, carbonic acid, and nitrogen. The latter is present only in minute quantity and seems to play no important role in the vital processes, its quantity in different parts of the circulation being approximately the same.

The amounts of oxygen and carbonic acid present differ, not only in the blood derived from various parts of the circulation, but also in their correspondence to the rapidity of the blood-current, the different temperatures, rest, labor, etc.

According to Setschenow, oxygen is contained in the arterial blood of man to the amount of 21.6 per cent, by volume. The amount carried by the venous blood differs. Ludwig and Szeltcow found 6.8 per cent, of oxygen by volume in the venous blood of nonactive muscles, and still smaller quantities in that of those in action. Oxygen is entirely absent, or present only in traces, in the blood of the asphyxiated. Zuntz states that the venous blood of the right heart contains on an aver- ^g^ 7- 1 5 P^r cent, less of oxygen than the arterial blood.

The proportion of carbonic acid contained in the arterial blood is usually forty per cent, by volume, but varies between thirty and forty per cent. It always corresponds exactly, or very nearly, to the amount contained in the air of the alveoli. Every change in the composition of the alveolar air must be followed by a corresponding change in the tension and the absolute quantity of the carbonic acid in the arterial blood. Again, the carbonic-acid tension of the arterial blood affects primarily the diffusion between the blood and the tissues ; hence any variation in the proportion of carbonic acid in the alveolar air, when continuing for some time, will cause a corresponding change in the proportion of the carbonic acid in the blood and tissues, where it is always found in considerable quantities.

The proportion of carbonic acid contained in the venous blood varies still more. According to Zuntz, the venous blood of the right heart contains 8.2 per cent, of carbonic acid more than the arterial blood. The average quantity is about forty volumes per cent. In the blood of the asphyxiated Holmgren found even 69.21 volumes per cent, of carbonic acid.

Almost all the oxygen in the blood is loosely held by the oxyhemoglobin, and only a small portion — 0.26 per cent. — is absorbed by the plasma or serum. The circulating blood does not appear to carry oxygen entirely up to the point of saturation. Of the carbonic acid found in the blood, the smaller portion — according to the examinations of Alex. Schmidt, Zuntz, and L. Frederiks at least one-third — is contained in the blood-corpuscles, by far the larger quantity being carried by the plasma and serum.

The carbonic acid in the blood- corpuscles forms a loose chemical union, first with the alkalies which there enter into combination with phosphoric acid, oxyhemoglobin, or hemoglobin and globulin; and, secondly, with the hemoglobin itself. The red blood-corpuscles do not contain enough alkali phosphate to be of importance in the formation of carbonic acid. In all probability the diphosphates present are converted into monophosphates and alkali carbonates when partial pressure of carbonic acid is increased, while, when the same is diminished by the preponderance of phosphoric acid, a reformation of diphosphates takes place and carbonic acid is again liberated. It is generally conceded that the blood-coloring matters, especially oxyhemoglobin, which by its presence in vactLo with bicarbonate of soda causes the liberation of carbonic acid, act similarly to acids ; and, inasmuch as the globuli have a similar action, they may also occur in the blood - corpuscles as alkali compounds. The alkalies of the blood-corpuscles die when thus found in combination with phosphoric acid, carbonic acid, and such parts of the corpuscles — e,g., the coloring- matter — as act similarly to acid. In the presence of a preponderance of or of a greater partial pressure of carbonic acid, bicarbonates may be formed at the expense of the diphosphates and the alkali compounds just mentioned; while, when partial pressure of carbonic acid is lowest, a reformation of the diphosphates and the alkali compounds will take place, and carbonic acid will be liberated from the bicarbonates.

The investigations of Setschenow, Zuntz, Bohr, and Torup, however, make it appear probable that hemoglobin itself, even in the presence of alkalies, can loosely bind carbonic acid. Bohr found, in addition, that the curve showing dissociation of carbonic-acid hemoglobin, and that showing increase or decrease of carbonic acid in the blood, essentially correspond ; and hence Bohr and Torup ascribe considerable importance to the hemoglobin itself, rather than to its alkali compounds, in the formation of carbonic acid in the blood. Moreover, hemoglobin possesses the ability to absorb the two gases, oxygen and carbonic acid, both independently of each other and simultaneously. Bohr believes that the granules of coloring-matter absorb the oxygen and that the carbonic acid is bound by the albumin component. The main amount of carbonic acid in the blood is found in the plasma or serum. It is more abundant in the serum than in the other constituents. We find the carbonic acid in the serum and blood-plasma distributed as follows: I. Apart is simply absorbed. 2. Of the remainder the larger part is in loose, the smaller part in firmer, chemical union.

The quantity which is simply absorbed can not be exactly determined. Setschenow estimates that in the serum of the dog it forms about one-tenth of the entire carbonic acid contained in the blood. The quantity of carbonic acid in firm chemical combination must be determined by the amount of alkali carbonates ; it is, however, not exactly known, inasmuch as the alkalies of the blood are not only associated with carbonic acid, but also with other components, especially with the albumins.

Part of the loosely bound carbonic acid of the serum which can be separated by the exhaust-pump is found as bicarbonate; in fact, alkali is the most essential and most important component uniting with carbonic acid in the blood-serum as well as in the blood itself.

The amount of the carbonic acid in the blood lessens with a lessening amount of alkali. Such is, for instance, the case when poisoning with mineral acid takes place. Thus Walter found only 2.3 volumes per cent, of carbonic acid in the blood of rabbits, into the stomach of which he had introduced hydrochloric acid. It seems as if, during the comatose stage of diabetes mellitus, the alkali of the blood was saturated to a large extent by acid combinations (oxybutyric acid). Minkowski found only 3.3 volumes per cent, of carbonic acid in the blood of a comatose diabetic.

The oxygen of the blood exists in dissociable combination with the hemoglobin; and this combination, the oxyhemoglobin, depends on a certain partial pressure of the oxygen, which pressure varies with the temperature. The same is the case with carbonic acid in the blood, that contained in the corpuscles as well as that in the plasma ; it exists there in combinations which depend to a high degree on partial pressure. As we see from the foregoing, quite a number of elements act together with carbonic acid, making it apparently impossible to decide the quantitative part of each single factor in the entire effect.

It is of great importance to know the amount of tension of oxygen and of carbonic acid in the blood, in order to decide the question of the exchange of gases between the blood and the alveolar air on the one hand, and the blood and the tissues on the other ; and especially to decide how far this exchange of gases takes place under the law of diffusion, and how far other forces may be active.

The change of gases in the tissues, the so-called internal breathing, takes place in the following manner : Oxygen leaves the capillaries to enter into the tissues, and simultaneously the main mass of the carbonic acid of the blood which is derived from the tissues leaves the latter and enters into the capillaries. The change of blood in the lungs, the so-called external breathing, is the taking up of oxygen by the blood from the air in the lungs, and giving up of carbonic acid to the latter.

These processes of the double gas exchange are not yet sufficiently explained. The question which is yet to be solved is : Does the exchange of these gases take place in consequence of the difference between their tensions in the blood and in the air in the lungs and the tissues respectively, or through the laws of diffusion, or are there other factors in operation ?

Oxygen in the blood exists for the most part as oxyhemoglobin. To find the tension of oxygen in the blood it is necessary, first, to consider the laws of dissociation of oxyhemoglobin. G. Huefner and others have examined this dissociation under temperature of 35° and 39"^ C. (95"^ and 102° F.), and their experiments have shown that when the partial pressure of oxygen is reduced to the level of the pressure existing in atmospheric air, there is no marked influence noticed in regard to the quantity of oxygen, either in the blood or in a correspondingly concentrated oxyhemoglobin solution. The investigators —

Paul Bert, Herter, and Huefner — have found by their experiments that the tension of oxygen in the arterial blood at the normal temperature of the body is equal to an oxygen partial pressure of 7S-8o mm. of mercury. The tension of the oxygen of the air in the lungs was compared with these figures.

Numerous investigations in regard to the composition of the inspired atmospheric air as well as the air of expiration have been published. These two kinds of air have on an average, at o"" C. and under pressure of 760 mm. of mercury, the following composition expressed in volumes per cent. :

Oxygen. Nitrogen. ^^^^^^^^^

Atmospheric air 20.96 79.02 0.03

Air of expiration 16.03 79-59 4-3^

The partial pressure of the oxygen in the atmospheric air — the barometer having the average 760 mm. — corresponds with a pressure of 159 mm. of mercury. The loss in oxygen which the air of inspiration sustains during respiration is therefore 4.93 per cent., while the air of expiration contains about one hundred times as much carbonic acid as the air of inspiration.

For the exchange of gases in the lungs the composition of the alveolar air is of paramount significance. Of the composition of this air in man we possess no positive but only approximate calculations ; the probable amount of carbonic acid contained in the alveolar air has been set down at 5.44 per cent., the amount of oxygen as 14.96 per cent. — the latter corresponding with a partial pressure of 114 mm. of mercury.

Bohr believes that the lungs take an active part in the absorption of oxygen; other authors have controverted this assumption. The present state of the question is such that we can not produce sufficient reasons for abandoning the view as yet generally adopted, viz., that the entrance of oxygen into the lungs takes place simply by means of diffusion ; and further, after what has been said of tension and dissociation of oxygen in the blood, it is to be supposed that the amount of oxygen in the blood, at least within certain limits, does not specially depend on the amount of oxygen in the atmospheric air. Indeed, it is known that the increase of the oxygen pressure, even to the strength of one atmosphere, has no essential influence on either the amount of oxygen taken into the lungs or the amount of carbonic acid which is exhaled.

Paul Bert found that animals placed in pure oxygen under a pressure of three atmospheres, or in ordinary atmospheric air under a pressure of fifteen atmospheres, have convulsions and quickly perish; whence it would appear that oxygen at high tension is inimical to life.

This oxygen intoxication is characterized by an extraordinary reduction of the consumption of oxygen and by the formation of carbonic acid. All organisms, animal as well as vegetable, succumb alike. Even seeds of plants which in general are possessed of great power of resistance lose for a certain time, when exposed to oxygen under high pressure, their germinative power. Oxygen exerts a deleterious effect on the different organisms when they are exposed to it for a greater length of time, even at a tension far below the one which kills quickly. Bert observed that the development of eggs and the metamorphosis of insects were injured by a long stay in pure oxygen under ordinary pressure. When we inhale pure oxygen its consumption and the formation of carbonic acid become diminished. The deleterious effects of excess of oxygen and overaccumulation of carbonic acid when occurring together cause an animal to perish even when neither of the two gases by itself is present in a dangerous dose.

Pflueger, in order to bring the remarkable effects of compressed oxygen nearer to our understanding, has called attention to its analogous behavior toward phosphorus. In pure compressed oxygen phosphorus does not give light and does not absorb oxygen; as soon, however, as sufficient nitrogen is added, or the pressure is diminished, the production of light takes place and the oxygen becomes absorbed.

Altho carbonic acid is a matter for excretion and life can be continued only when this gas is eliminated from the system regularly by rhythmically recurring respiration, it would be erroneous to deny it any further role in the economy of the system. The carbonic acid in our system, with its normal quantitative changes, seems to be necessary to excite important vital functions, especially respiration and circulation. The symptoms of intoxication making themselves noted at the respiratory pneumogastric and the vasomotor centers when excessive ouantitles of the gas have been inhaled may be explained, to some extent at least, as suggestions of normal physiological processes.

The tension of the carbonic acid in the blood has been calculated in various ways by Pflueger and his pupils, Wolfberg, Strassburg, and Nussbaum. According to Strassburg, it is 2.8 per cent, of one atmosphere, corresponding to a pressure of 21 mm. of mercury. Nussbaum found in the blood from the right heart a carbonic-acid tension of 3.81 per cent, of one atmosphere, corresponding to a pressure of 28.95 mm. of mercury. Bohr, by his experiments on carbonic-acid tension, arrived at other figures.

J^ comparison of the carbonic-acid tensions in the blood and in the tidal air showed in several instances a greater carbonic-acid pressure in the air of the lungs than in the blood, and the maximum of the difference was 17.2 mm. in favor of the air of the lungs. The alveolar air contains more carbonic acid than the air in the bronchi; therefore Bohr's experiments show that the carbonic acid in the alveoli has moved against the higher pressure. It has been assumed that the oxygen has a certain significance in regard to the elimination of carbonic acid in the lungs. Some attribute to oxygen the power to drive the carbonic acid out of its combinations in the blood. Experiments seem to show that the oxygen from the alveoli, entering into the blood, intensifies the tension of carbonic acid, and hence that the oxygen becomes an auxiliary factor for the elimination of carbonic acid. This assumption, however, has met with opposition, and the question is yet an open one.

Concerning the elimination of carbonic-acid gas in the lungs, we are still without convincing reasons for abandoning the generally adopted view/according to which the carbonic-acid gas coming from the blood enters the lungs simply by the law of diffusion. There is a considerable difference of pressure in regard to the oxygen in the blood and the oxygen in the tissues, and, owing to this difference of pressure, the tissues are supplied with the necessary amount of oxygen. Quite the opposite is the case with carbonic acid; the tension is higher in the tissues than in the blood, and all the investigations thus far made have produced no evidence against the assumption that carbonic acid from the tissues enters the blood simply by the laws of diffusion.

Considering even superficially the quantities of oxygen in the blood, it appears at once plain enough that the main amount can not have been absorbed physically; for the serum of the blood, as a solution of different substances, absorbs less oxygen than pure water. It can absorb hardly 0.3 volume per cent, of oxygen from the atmospheric air at the ordinary temperature of the body. In reality, however, 2 [17]

arterial blood holds not less than seventy times this quantity of oxygen.

The same law applies to carbonic acid, the larger part of which, as has been shown, is held in chemical union in the blood and can not to any great extent be absorbed physically. The partial pressure of the carbonic acid in the blood is much too small to allow of the gas being simply absorbed. The carbonic-acid tension in the venous blood of the dog is 41 mm. of mercury. This would permit 2. 5 volume per cent, of carbonic acid to be physically absorbed therein, while, according to the same reasoning, arterial blood would show only about half that amount. In reality, however, the venous blood contains forty-six and the arterial thirty-eight volume per cent, of the gas.

A comparison of the gases of the arteries with those of the veins is of great importance, because it furnishes directly the evidence that real processes of combination do not occur to any considerable extent in the lungs, but that almost the whole amount of oxygen which has entered the lungs can be separated from the blood of the arteries by means of the exhaustpump.

The mass of inspired air has to be divided, in regard to its action on the renewal of the air in the alveoli, into two parts. A certain amount remains in the upper air-passages and is removed again by expiration. The rest enters into the alveoli to mix with the air which is already there. On account of the smallness of each single infundibulum, it is likely that the diffuse mixture of old and fresh air takes place instantaneously, while the bronchial tubes are too long to allow the exchange of their gases with those of the alveoli by diffusion, which could hardly be accomplished in the time between two respirations.

The next process in respiration is that air from the alveoli takes the place of the expired contents of the bronchi, and only when the extent of the expiration exceeds in volume that of the air-passage will alveolar air pass out directly. The movements of respiration, therefore, can have but little success when the volume of each expiration does not exceed that of the air-passages — that is, does not more than exhaust the contents of the air-passage. Thus a very superficial breathing will only insufficiently ventilafe the alveoli, even tho the frequency of respiration is increased. The residual air, which during lifetime can not be expelled from the lungs, has been calculated by Vierordt to be from 1,230 to 1,640 c.c.

The expired air is richer in carbonic acid and poorer in oxygen in proportion as the larger part of it comes from the alveoli — that is to say, the more profound the expiration.

Chapter II

tllSTORY OF THE USE OF THE CAR- BONIC ACID IN THERAPEUTICS

The application of carbonic-acid gas for therapeutical purposes can be traced to the earliest times. We all have read of the stone of Memphis, which stone was pulverized, dissolved in vinegar, and applied to parts of the body in order to anesthetize them. Dioscorides and Plinius speak of this stone. But exact observations of the gas were not made before the seventeenth century.

Mineral springs, with their large volume of carbonic-acid gas dissolved in water, have served for therapeutical purposes long before carbonic acid had been demonstrated. They often present remarkable appearances when relieved from subterranean pressure, by losing their gases with more or less rapidity, according to the tension to which they had been subjected. Some of them issue from the earth with rumbling, gurgling, or hissing noises; others do so only at regular intervals, and rise to a height of from twenty to forty feet ; some ascend from the bottom of the sea, of lakes, and of rivers; others appear many thousand feet above the level of the ocean ; some break at a boiling heat through a crust of ice and snow; others issue with icy coldness near shrubs and flowers ; some destroy vegetation in their immediate neighborhood, while others penetrate and cover organic structures with calcareous incrustations and preserve them.

Such phenomena were replete with wonder and attracted the attention of philosophers from an early period. Supernatural properties were ascribed to the springs. Strange theories were propounded regarding their origin, and wonderful tales and fables were current of their curative powers.

Strabo relates that the springs of Hierapolis imparted a red color to the roots of trees and shrubs, and that the juices of the latter, when mixed with the water, produced a purple liquor which was used for dyeing wool. We shall see how this reaction of carbonic acid was interpreted by Hoffmann, who lived in the seventeenth century. Philostratus, when speaking of the sanguinary battle which the Greek army fought with Telephus, on the banks of the river Caicus, states that the wounded Greek soldiers who resorted to Agamemnon's spring, near Smyrna, were all restored. According to Herodotus, a spring in the country of the Ichthyophagi (fish-eaters) prolonged life to beyond one hundred and twenty years. A spring in Chios caused insanity; another in Magnesia improved the voice of singers ; and the spring of Alysson was a specific for hydrophobia. The springs of Lethe and Mnemosyne are often mentioned in classical literature; the former gave oblivion and the latter memory.

Little is mentioned of mineral springs in the Old Testament. According to the Genesis, Anah, the father of Esau's wife, discovered some thermal springs in the desert; and in the second book of Kings we find mention made of a spring at Jericho which made the ground barren, and was made wholesome by the prophet EHsha throwing salt into it. But from the New Testament we learn that the Jews, before Christ, used thermal waters extensively. " There lay a great multitude of impotent folk, of blind, halt, and withered, in the porches of the lake Bethesda, by the sheep-market at Jerusalem, waiting for the moving of the waters ; and whosoever first after the troubling of the water stepped in, was made whole of whatsoever disease he had.*' This water had a reddish-brown color, from a sediment of ochre probably deposited by the escape of carbonic-acid gas; sulfur was also found in the mud, and the more rapid disengagement of carbonic acid and sulfureted hydrogen when the water was stirred up may account for its increased curative power at such time.

Mineral springs play an important part in the religion of the ancients. The priests of iEsculapius erected temples to the god of medicine in the vicinity of mineral springs. They were not only provided with theaters and places of amusement as our fashionable modern waterresorts, but also with hospitals and medical schools for the instruction of students. The most important of these were the springs of Nauplia, in the sacred grove of ^Esculapius. They have been described by Pausanias, and from the remains of their structures we can judge of their former greatness. The water of Nauplia has been analyzed by Landerer and found to contain carbonic acid.

The Castalian spring had a temperature of only 33° C. ; in this spring Pythia had to bathe before ascending the tripod in the steaming cave in Apollo's oracle at Delphi. There are copious exhalations of carbonic-acid gas in that cave, and from the short and incoherent sentences which the priestess uttered in her excitement and paroxysms the prophecies were drawn. Such were also the gas-springs of Dodona, the most ancient oracle of the Greeks.

Paracelsus (1493-1541) made use of carbonic-acid gas for therapeutic purposes, calling it Spiritus Sylvester. He knew that the gas produced by burning charcoal is identical with that developed when limestone is heated to a high degree. Paracelsus's full name was Philippos Aureolus P. Theophrastus Bombastus Paracelsus ab Hohenheim. Paracelsus examined most of the chemical products with which he became familiar as to their therapeutic properties, saying that the true usefulness of chemistry was not to make gold, but to prepare healing remedies. For his labors in this direction, we can hardly overestimate his merits. Many medicines which are highly valued to this day were discovered and introduced by him. The internal administration of mercury in different forms, and several preparations of lead, of antimony, of sulfur, of copper, and of iron were first taught by Paracelsus. With his method of extracting from medicinal plants the essence — the quintessence, as he called it — and prescribing this essence instead of the whole plant, he was far ahead of his time.

Jan Baptist van Helmont (i 577-1644), who can be regarded as one of the greatest chemists who preceded Lavoisier, was the founder of pneumatic chemistry. He was the first who used the word gas as a generic name for all elastic aeriform fluids, in order to distinguish them from atmospheric air. He paid much attention to the study of gases, and showed that they entered into the composition of the atmospheric air. He first gave a description of carbonic acid, which he called gas Sylvester, and described its development, when the acid is brought into contact with limestone or potash, at wine and beer fermentation, during putrefaction, its appearance in the stomach, and showed that it was contained in the mineral water of Spa, that it was rising from the ground in some places, for instance, at the dogs' grotto near Naples. However, his distinction of the different kinds of gases was still imperfect; he knew no means to handle the different gases he had developed. Under the name of gas Sylvester, which he sometimes designates by the term gas carbonicum, he understood principally carbonic acid.