[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 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.

They

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 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. In 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.

Re

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:

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

vein and that of the hepatic veins is determined, the temperature observed is represented by the following figures: -

Temperature of the blood of the portal vein,

40.2°C.

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

lieved that the kidney manufactures urea, considering the renal parenchyma as a true gland. However, in spite of these reservations, and especially if one considers the most recent experiments of Slosse, it appears demonstrated experimentally that when the hepatic cells are destroyed by a proceeding which consists. in applying a ligature to the intestinal arteries, by which the death of the hepatic cells is induced, the secretion of urea disappears. It appears, then, to-day demonstrated that if the organic combustions may produce urea in all parts of the body, it is especially the liver which plays the most important role in the production of urea.

The attempt has even been made to carry the problem farther, and to ascertain from what elements the liver produces urea, and it has been thought that it is with ammonia and a nitrogenized. radical that the liver produces urea. This view is based upon the experiments undertaken by Minkowski, Naunyn, and Stern, who have experimented upon animals by extirpation of the liver. They observed that ammonia appeared in the blood and in the excretions. However, this fact seems not yet to be absolutely demonstrated, and it also appears that the results differ according to the animal experimented upon. Neubelthau, by operating upon frogs, has arrived at nearly analogous results, finding ammonia in the urine of frogs from which he had removed the liver.

This is not the only function of the liver in relation to the blood. It now remains for me to speak of the hæmatopoietic functions of the liver. You know that the liver was considered by the ancients as a blood-making organ, and recent experiments seem to furnish ground for belief in Galen's hypothesis. However, the opinions which have been expressed upon this subject are absolutely contradictory, it being maintained, on the one hand, that the liver forms blood globules, and on the other, that it destroys these globules. Lehmann, who supported the .first of these opinions, relying upon experiments made upon the dog and the horse, always found in the hepatic veins more blood globules than in the portal vein. The following figures given by Lehmann indicate the proportion of globules and plasma found in 1000 parts of blood:

This opinion has been combated by Schultz and Mandl, who have maintained that the liver destroys red globules, and that by the action of cholates." This destructive action, according to them, produces hæmapheine, and perhaps bilirubin. But, since methods for counting the blood globules have been perfected, it has been shown that the liver has little action upon the blood, and if any action exists, it is more destructive than productive of red globules. The following figures, given by Prof. Hayem, show the difference between the number of globules found in the blood of the portal vein and the hepatic veins :

BLOOD OF THE PORTAL VEIN.

According to this analysis, the blood. of the portal vein is richer in red globules than that of the hepatic veins, but the difference is small.

In concluding these remarks respecting the role played by the liver in nutrition, I must say a few words respecting the action of the liver in the production of fat. Many physiologists have maintained the opinion that fat must have some other origin than that of the introduction of fatty matters in the food. In experiments made upon certain animals, and especially upon geese, Boussingault, after Liebig, had demonstrated that the quantity of fat accumulated in the bodies of these animals greatly exceeded that contained in the corn upon which they were exclusively fed.

Persoz studied the problem with greater exactness, and maintained that in the goose, in particular, the liver performs the function of transforming the starchy matters and sugar into fat. This opinion, which gave to the liver the exclusive role in the transformation of starchy and fatty matters into fat, is exaggerated. It is

probable that the entire system participates in this transformation. In relation to the dietetic regimen of obese patients, I have shown that in such cases starch and sugar are transformed into fat.

(To be continued.)

Consumption of Meat from Tuberculous Cattle. It is only necessary to read the medical journals and public press to see the great diversity of opinion that exists in the minds of the medical profession, scientists, and the public at large, concerning the danger that is incurred by the use of the flesh of animals suffering from tuberculosis. From the reports presented to the Congress of Tuberculosis in Paris, and from more recent investigations by Mr. Arloing, who has been experimenting in the inoculation of meat juice of tuberculous animals, the majority of physicians have arrived at the conclusion that the flesh of possibly one sixth of these animals is capable of causing phthisis. Various experimentalists, including Mr. Nocard, have by their work demonstrated the same fact. On the other hand, Mr. Perroncito (Centralblatt fur Bakteriologie, XI, page 429) has always defended the opinion that there was little danger in the use of such meat, and cited in argument the negative results of his own experiments. He has recently made new experiments on the subject, with meat from animals which had been isolated because they were suffering from tuberculosis with advanced lesions.

More than 200 rabbits and as many guinea-pigs were inoculated under the skin, or in the peritoneum, with meat juice from tuberculous subjects. None of these animals, killed after eleven months, presented any sign of tuberculosis.

beeves inoculated under the skin with beef juice, remained immune. Four sixmonths pigs of Italian breed, nourished four months on tuberculous meat, presented at the autopsy no tubercles. Twelve others, two months old, nourished five months the same way, also escaped. Two young Yorkshires, nourished in the same fashion, failed of infection in three months. These animals were fed later on with intestines of beeves containing tubercles, all with impunity.

With these results of Mr. Perroncito before us, it should never be forgotten, however, that the other experimentalists

mentioned above, equally as exact and equally learned, together with daily observations as mentioned above, have reached results just opposite, which do now and always will have their value. The question at this time is one which must be considered in the light of danger; for we must remember that if some experiments with vaccination give negative results, as many can be found which give positive results, and constitute as many indications of positive danger. Furthermore, it should not be argued for a moment that diseased meat should form a portion of our diet, even though it were non-infectious.

Glandular Tuberculosis.— Tubercular lymphangitis, it is now generally conceded, is due to the bacillus of tuberculosis. In fact, the vast majority of cases of adenites in the young or adult are of bacillary origin, and constitute local forms of tuberculosis.

Dr. Samuel Lloyd, of Randall's Long Island Hospital, reports between 200 and 300 cases in which lymphangitis seemed to have been produced by the germ of consumption. The points of entry of the microbes are, according to the author, injuries to the scalp, furuncles of the ear, face, etc., abscesses, decayed teeth, injuries to the mouth and nose, such as ulcerations of the gums, fauces, nostrils, etc. The bacillus of tuberculosis is almost always found, the number varying according to development of the disease and size of affected glands. The primary pulmonary lesions were not present in any of Dr. Lloyd's cases. The treatment that seems the most successful is complete, careful excision of all the affected glands. In one instance Dr. Lloyd removed eighty-five enlarged glands.