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have been deprived of its mainstay; and the tide of clinical evidence tending to show the simply contagious nature of typhoid fever, seemed to have gathered sufficient force to sweep off the grounds of scientific medicine a structure which had been erected and finished by untiring energy and wonderful ingenuity.

For years previous to Eberth's discovery, clinicians, restive under the therapeutic, and, in a measure, prophylactic nihilism, which the prevailing epidemiological notions indirectly implied, had been at work to undermine Pettenkofer's edifice by the force of argument based upon the facts gathered at the bedside and in the surroundings of typhoid fever patients. The demonstration of Eberth of a bacillus found invariably in the organs most affected by the morbid process in every case of typhoid fever, seemed to furnish the missing link in the chain of those arguments.

Inadequacy of Bacterial Demonstration. - But the simple demonstration of a bacillus in all cases in which the clinical picture was that of unequivocal typhoid fever, though accounting satisfactorily for the pathogenesis of the disease as such, fell far short of explaining all the problems, which, in the course of the histories of epidemics, had presented themselves for solution, and which, since the discovery of the microbe, were constantly multiplying.

Pettenkofer's Theory. Above all, there was the remittent character of the epidemics which called for a factor back of the bacillus, and which seemed to be felicitously furnished in the form of the hypothetical, local, and temporal predisposition. After the germ, formerly only a logical postulate of Pettenkofer, had been found, it remained to be proven that under certain atmospheric conditions coupled with a low level of the ground water, the bacillus not only underwent a maturing process, necessary for a successful invasion of the human organism, but also that it was dispersed throughout the atmosphere in order to reach its victims. This proof has never been furnished. Besides, many of the phenomena which formerly were utilized by Pettenkofer in favor of his theory, have been interpreted by modern observers in an opposite sense. It seems, therefore, that, as in cholera, so in the typhoid question, one after another of Pettenkofer's arguments have to yield

to the doctrine of contagion as against that of the miasmatic origin of disease, in spite of the fact that bacteriology in its present state is still very far from explaining everything, and that we are still in absolute darkness as regards some of the most vital points touching the question under discussion.

Morphology and Biology of the Typhoid Bacillus. In order to have a proper appreciation of the difficulties barring the road to exact knowledge, but at the same time, of the palpable and demonstrable results which have been obtained through the study of Eberth's microbe, a short account of what we know of its forms and life habits may be in order at this place.

Polymorphism. Unfortunately, the most elementary of all criteria, its form, offers nothing characteristic. It looks like many other bacilli, and, what is worse, varies very much according to the media on which it grows. This polymorphism it shares with many water and ground bacteria, and with a number that are normal inhabitants of the intestinal The one most frequently met with, and with which it is most apt to be confounded, is the bacillus coli communis. The ends are rounded off, so that a short specimen of the microbe may give the impression of an ovoid-shaped coccus. Under some conditions it develops seemingly into threads, which on close inspection, however, are found to consist of a continuous chain of bacilli.

Motility. Their motility is effected by vibratile cilia (flagella), of which the fully developed bacillus possesses from three to six, or more. The larger individuals have a snake-like motion.

Nutrient Media as Affecting the Growth of the Microbe. Like many other similarlooking bacilli, it grows in gelatine at ordinary temperatures, without liquefying it. Hitherto it has been held that its growth on potatoes is quite characteristic. But a close research has demonstrated that the thin, glistening, almost invisible film which covers the potato, is produced by other bacteria likewise; and that, when the surface of the potato is rendered alkaline, a yellowish brown covering results. If to this uncertainty of the potato culture, which up to a short time ago was held to be absolutely diagnostic, is added the fact that Koch found five bacilli which in all respects are similar to, or even

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identical with (excepting their pathogenic properties), the typhoid germ; and that Kitasato, a Japanese physician, and one of the ablest and most reliable observers of Koch's school, has a list of sixteen different bacteria, all of which may be easily confounded with our microbe; it becomes evident how perplexing may be the task of demonstrating the presence of the typhoid bacillus under certain conditions; when, for instance, water or solid substances are to be examined for the typhoid germ. Of course, there is little difficulty in determining it when the material for examination is taken from the living body or from one of the organs in which it is known to form colonies by preference.

Organs Harboring the Bacillus.—These organs are, besides Peyer's patches, the spleen, liver, and mesenteric glands. Here the bacilli congregate and entrench themselves; only occasionally are they found in the blood. I myself have examined the blood of six patients without being able to demonstrate their presence either microscopically or by culture. tapping the spleen with a hypodermic needle, they have been found by several investigators in the blood thus obtained;

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a diagnostic means, however, the spleen puncture does not, as a matter of course, recommend itself. Sometimes they are found in the brain and spinal cord. One observer claims to have discovered them in the roseolar eruptions which, he says, are the result of bacterial capillary embolism. This observation has not been verified. In two cases which I examined, no bacilli could be demonstrated. More probably the roseolar spots are the result of the action of toxic materials circulating in the blood.

Difficulties in the Way of Investigation. -But the chief difficulty barring a successful study of the typhoid bacillus, lies in the utter absence of any animals sponthe taneously susceptible to disease. Rabbits, guinea-pigs, rats, and mice have been inoculated; and in isolated instances the characteristic lesions in Peyer's patches were the result of such inoculations with pure cultures. But generally there was no infection, merely a toxæmia,'

1 In a true infection the bacteria, when introduced into an animal organism, develop and multiply, and the number of germs is, theoretically at least, of no importance. A toxæmia will result secondarily from the poisonous products secreted by the pathogenic germs. In toxæmia, pure and simple, it is the amount of bacteria together with their poisonous secre

which made the animals sick or killed them. And it is not the typhoid bacillus alone which possesses the power of producing both intoxication and ulceration of Peyer's patches in animals. There are many ordinary water and ground bacteria that are not known as having pathogenous power, and yet they yield the same result when introduced into the circulation of animals.

It seems, however, that of late, white mice have been successfully infected by some French experimenters. The introduction of typhoid bacilli direct into the duodenum analogously to Rietch's and Nicati's experiments with the cholera germ, seem to have been negative.

Variation in Virulency of the Bacillus.— Another great obstacle to obtaining uniform results is the changeableness of the virulence of the typhoid microbe. When bacteriology was still in its infancy, the notion prevailed that there was not only a constancy of form, but also a constancy of virulence, in the various species of pathogenic and other bacteria. In fact, this was one of the fundamental doctrines in the new science. Pasteur was the first to do away with the latter error, and today there is nothing so well established, but at the same time so confusing and leading to contradictory results in experimenting, as the variability of microbian virulence.

The typhoid bacillus is no exception to the rule, but may, on the contrary, be looked upon as a paradigm. Just as the cholera vibrion may be changed from an exceedingly poisonous to a perfectly harmless state, and vice versa, so the typhoid germ is able to acquire and lose pathogenous properties, by varying surrounding conditions.2

tions, that determines the result; absence of any effect, or intoxication followed or not, by death. In toxæmia, then, the microbe may be found in the blood during life or after death; but it has been simply preserved, though perhaps in a viable

state.

To make this unstableness of poisonous properties of the lowest forms of plants, the microbes, comprehensible, analogous examples in higher plants are generally adduced to the text-books on bacteriology. The bitter almond is in every respect like the sweet almond, and the bitter almond tree has been shown to be the parent of the sweet variety; but there are the well-known poisonous properties of the bitter, which is the only difference between it and the sweet almond. Another example is found in foxglove. When Linnæus visited Lapland, he was astonished to see the natives eat this plant made up as salad. He ate of it himself, and found that what is regarded as one of the most poisonous plants in the moderate zone, especially in mountainous regions, is perfectly harmless and used as a vegetable in the extreme North. Perhaps the variability of typhoid fever epidemics as to morbility and mortality, is to some extent attributable to the changeableness of virulence in the bacillus, although this is certainly not the only factor capable of explaining it.

(To be continued.)

TRANSLATIONS AND ABSTRACTS shall be able to judge the true role which

[THE articles in this department are prepared expressly for this journal.]

THE LIVER AS A BLOOD GLAND.

BY DUJARDIN BEAUMETZ,

Member of the Academy of Medicine, Physician to the Cochin Hospital, Paris.

Translated by J. H. Kellogg, M. D.

THE ancients regarded the liver especially with reference to its relation to the blood. Struck by its special relation to the liver, and the great volume of blood which enters and departs from it, they considered the liver as an abdominal heart, and Galen maintained that the liver was the organ in which the more refined portions of the blood were elaborated. He even held that the quantity of blood produced by the liver was so great that a disturbance of its functions gave rise to the gravest maladies.

You will also find a trace of this theory concerning the liver in the Talmud Bekhoroth, one of the twenty-one treatises on the Talmud of Babylon. One of the characteristic phrases used, is this, from Rab Khahana, "The liver is the source of the blood."

Not only were the ancients acquainted with the importance of the circulatory system, but they were not ignorant of the intimate relation which exists between this circulation and hemorrhoids, to which they gave a very important role. They maintained that the sudden disappearance of hemorrhoids provoked grave symptoms, a fact which you will find many times cited in the works of Hippocrates. Then came a period in which the liver was considered a useless organ. But in the seventeenth century, Stahl contended against this opinion, and attached great importance to disturbance of the portal circulation.

We will study first the circulation of the blood in the hepatic gland, then the modifications which the blood undergoes in traversing this gland. You will see, later, that this study is necessary, if one desires to understand the role played by congestion of the liver, either as a primary affection or as a secondary disorder. It is only after having made a very careful study based upon the most recert physiological discoveries, that we

hepatic congestions play in infectious or other maladies in which this congestion appears.

In order to understand the anatomy of the hepatic circulation, it is necessary to review briefly the study of the hepatic lobule. It should not be forgotten that the conception of the hepatic lobule which was entertained by Hering and Kiarnan has been profoundly modified in recent years by the works of Sabourin. Hering took for the basis of the lobule the blood-vessels which it received. This polyhedric lobule presented at its base the afferent veins which empty into the hepatic veins, while, on the contrary, the central vein of the polyhedron belonged to the portal vein, and entered the vascular network established between the veins of the periphery and the central veins.

Sabourin, basing his views upon the results of investigations in pathological anatomy, abandoned the idea of hepatic lobules for that of biliary lobules, taking for the basis of his system the biliary ducts rather than the afferent or efferent veins. The accompanying figure indicates very clearly the scheme of this theoretical conception of the biliary lobule. At the base of this lobule is found a biliary duct (b), a terminal branch of the portal vein (p), and one of the terminal branches of the hepatic artery (a), while, on the contrary, at the periphery of this biliary acinus are found the branches of origin of the hepatic veins. Leaving the periphery of the biliary acinus, the efferent veins pass on to empty into the inferior vena cava. cross the liver directly, and are distinguished from the portal vein by the fact that, being adherent to the parenchyma of the liver, they remain open when the tissues are cut; while, on the contrary, the branches of the portal vein protect the body of the capsule of Glisson which envelops them, and collapse after a section. Finally, we should add that the hepatic veins, like the portal veins, are devoid of valves.

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It is not necessary to dwell here upon the origin of the portal vein. You know that the three great veins which contribute to its formation, are the splenic, the superior mesenteric, and the inferior mesenteric. The union of these three great veins at the border of the head of the pancreas, forms the trunk of the hepatic vein.

All the blood distributed in the intestinal mucous membrane passes through the liver by the portal circulation. It is necessary to note here, also, that there exist some accessory portal veins which Sappey described in 1859, and which are divided into five groups, to which he has given the following names: Gastro-hepatic, cystic, nutrient veins, veins of the suspensory ligament, and umbilical or paraumbilical veins.

To this portal circulation, which constitutes the dominant fact of the liver as a blood gland, it is necessary to add the nutrient vessels which are furnished by the hepatic artery. The absence of valves in the portal vein, the absence of surrounding muscular masses, aiding by their play the movement of the blood, the presence of a capillary network to be crossed in the interior of the liver, and finally the vertical arrangement of all the vascular network, are so many circumstances which oppose the passage of the blood from the intestine to the inferior vena cava. But to these causes which hinder the circulation, it is necessary to oppose those which, on the contrary, favor the course of the blood.

The one

which is certainly the most important of all others, is the respiration, which acts in two ways: In the act of inspiration the diaphragm is lowered, thus compressing the entire abdominal mass, and so causing the blood in the abdomen to pass toward the vena cava. On the other hand, by this same act there is created a partial vacuum in the chest, by means of which the blood is drawn toward the right auricle.

Rosapelly, who wrote in 1873 a remarkable thesis upon the conditions of the circulation in the portal vein, has demonstrated this action of the respiration. In fact, when one determines, in an animal, the pressure of the blood at its entrance and at its exit from the liver, it is observed that the pressure in the portal vein before its entrance into the liver, oscillates, in a dog, between 7 and 20 millimetres of mercury, while at its exit from the liver this pressure is only 3 or 4 millimetres, and is even ordinarily negative to the extent of 7 to 8 millimetres. The act of inspiration is one of the most important factors in the hepatic circulation; consequently any disturbance of the respiratory movement, and particularly anything which interferes with inspiration,

disturbs and obstructs the hepatic circulation. We shall see what conclusions it is necessary to draw from this fact, when we study the pathogeny of hepatic congestions and their treatment. To this action of the respiration, and, in particular, of inspiration, upon the hepatic circulation, it is necessary to add contractions of the walls of the portal vein. The walls of the portal vein possess a muscular layer sufficiently thick to produce rhythmical beating of its trunk.

Rosapelly has also studied the rate of the circulation in the portal vessels, employing prussiate of potash and introducing 1 gram of this substance into the blood of the portal vein. This substance is found in the blood of the hepatic veins, 8 seconds after its introduction. At the end of 25 to 30 seconds, the maximum quantity of the prussiate is found, and at the end of 1 minute, no trace of the salt is to be found in the hepatic veins. It should be understood that this experiment is made under conditions in which the influence of respiration is operative on the portal circulation. When the respiration of the animal experimented upon, is disturbed, there is great delay in the appearance of the prussiate of potash. lying upon experiments made upon the dead liver, and employing the method of artificial circulation devised by Ludwig, Rosapelly arrived at the conclusion that the rapidity of the circulation in the portal vein is 33 millimetres per second. the main trunks of the vein, this speed is only 22 millimetres per second. The velocity still further diminishes in the capillary network, where it is only 45 millimetres per second, while it is 16 millimetres in the hepatic veins.

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Rosapelly has also studied the causes of obstruction of the circulation. He has shown, first, that when the pressure of the blood in the hepatic veins is equal to that of the portal vein, the circulation is arrested. As to the arterial circulation, it is arrested when the pressure of the hepatic veins is raised, although still remaining inferior to that of the portal vein. We learn, from this, the fact that the circulation is much more active in the portal vein than in the hepatic artery, and that any disturbance in the vena cava superior or in the right auricle, is sufficient to induce modifications in the arterial circulation of the liver, that is to say, in that portion of the cir

culatory system of the liver which is charged with the nutrition of the hepatic gland.

As to the quantity of blood which passes through the portal vein in 24 hours, it is considerable, since in a dog of 20 kilograms (44 pounds), Flogga has found a flow of blood of 500 grams (17 ounces) per minute, making nearly 720 kilograms of blood passing through the liver in 24 hours.

Further, Nonneret has shown that the liver can triple its volume and weight under the influence of vascular stasis. Finally, let us not forget that the nervous system has a considerable influence upon the hepatic circulation, and that this portion of the circulatory system may be profoundly modified by lesions of the cord, of the great sympathetic, and even by the pneumogastric.

I come now to speak of the modifications which the blood undergoes in its passage through the hepatic gland. Considered as a whole, the modifications which the liver effects in the blood which passes through it, relate to the water, the albumen, and the fats, as shown in the following table

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There is a diminution in the percentage of water, in that of albumen, and also in that of fat. The hepatic cell, then, modifies the blood distributed to the surface of the intestine; and when we recollect that the intestinal vessels absorb, at the surface of the mucous membrane, water, peptones, and perhaps a certain quantity of fatty matters, it is easily understood that the liver plays an important role in removing thus from the blood, water, albuminoid substances, and fats, which have been introduced into it. But how is this modification effected? Have we here a true combustion? This question allows me to approach one of the most delicate points of this question of the liver as a blood gland; namely, the liver considered as an organ for the production of urea. Galen believed the liver to be a heat producing organ, a fact which we can understand when we recall the numerous chemical processes which take place within the hepatic parenchyma. When the temperature of the blood of the portal

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Temperature of the blood in the hepatic veins, 40.6°C.

The blood of the hepatic veins has a more elevated temperature than that of the portal vein, but this is a point of secondary importance, for it may be easily understood that the glycogenic function, and even the biliary secretion, may be a cause of this elevation of temperature.

Urea was discovered in the urine by Rouelle the younger, in 1772, and the experiments of Heynsius, Stokvis, Fürher, Ludwig, Meissner, and Cyon, showed by numerous proceedings that the liver contains urea, and that the blood, in passing through the gland, becomes charged with this substance. Fourcroix and Vauquelin, in 1808, affirmed that variations in the production of urea are connected with diseases of the liver.

Murchison, in 1874, united the various theories, and concluded that urea exists in considerable quantity in the liver, and that it is formed there. Finally, in a work which attracted great attention, Brouardel, in 1875, arrived at the conclusion that the quantity of urea secreted in 24 hours is dependent upon two principal causes: 1. The integrity or the disturbance of the hepatic cells; 2. The greater or less activity of the hepatic circulation.

However, this opinion is not admitted by all, and a great number of physiologists, adopt the opinions expressed by Dumas, who believed that urea results from the oxidation of albuminoid matters in the body in general, an opinion based upon the celebrated experiment of Bèchamp, who showed by oxidizing albuminoid matters with permanganate of potash, that urea may be obtained artificially, and it is admitted that a direct relation always exists between nutrition and the production of urea. Thus the opponents of the theory that the liver is the only source of urea, hold the opinion that the diminution in the secretion of urea in cases of hepatic disease is due to the fact that these disorders induce a disturbance of the general nutrition.

It should also be mentioned that Hoppe-Seyler, Hoppler, and Zalesky be

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