Pyelovenous Backflow in the Human Kidney1

PYELOVENOUS BACKFLOW IN THE HUMAN KIDNEY 1 FELIX FUCHS Received for publication January 10, 1928 L

SCOPE OF PROBLEM, REPORT ON LITERATURE AND ANIMAL EXPERIMENTS

The peculiar development of the kidney, essentially different from other glandular organs, stipulates the finding of special anatomical relationships between the activity of this organ and its excretory ducts. usual, morphology dominates the pathological and functional effects, an exposition of some of which shall be offered in the following investigation. The embryonic pronephros and Wolffian body are segmental organs. The elementary components are allotted to a series of embryo. In the deYelopment of the normal segments of kidney, this segmental arrangement is probably lost; but Felix, Keibel, Schreiner, etc. find that it remains. The completed kidney at any rate is formed by the concentration of the segments. concentration not only embraces the secretory glandular components, but the vascular apparatus and excretory system as well. During this developmental phase, we may observe the significance of topographical relations between the vascular system of the kidney and its excretory system. The intimacy of such a relationship not only extends to the smallest ramifications of the excretory where the urine is formed, but also to the grosser portions of the tubular system which collect the urine. Even though the ~,~,v,~,,,~ just described have provided microscopically a fruitful field histology, physiology and anatomy for a 1 The original of the article appeared in the Zeitschrift for Urologische Chirurgie, Band XXII, Heft 5/6. The translation was made by Dr. Frank Hinman, Sa,n Francisco,

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long time, the gross relations between the vascular and urinary systems have only recently been recognized as important. We believe that the increasing interest in urology evidences a need for the most exact anatomical and physiological foundations. The object of this communication is a consideration of pyelovenous backflow, the particular anatomical and hydromechanic peculiarities of which should be established. Anatomists have observed this phenomenon for a long time, but it is only within the last ten years that it has been recognized by experimental and clinical workers. If one injects fluid into the ureter of a human or animal kidney after removal, this fluid often flows out by way of the renal veins, because of a direct con1,1-ection between the vascular system and the upper portions of the kidney pelvis. This is so easily shown that one wonders why the old anatomists did not know of it. But, since it is not referred to in old anatomical literature, its occurrence was probably considered only as a disturbing element which unfortunately made the demonstration of typical injection preparations more difficult. 2 An attempt to establish the practical significance of this phenomenon has been made through animal experiments. But animal experiments are not exactly analogous to the conditions in humans, therefore it is important to ascertain the role, if any, the pyelovenous backflow plays in human pathology and exactly what this role is, which is the main object of the present paper. First, however, a short survey of the literature is necessary. I can partly coordinate my views by citing some very instructive work by Hinman and Lee-Brown (1). I can, however, quote many important publications overlooked by these authors, which may be due to the fact that there has been no well-rounded presentation of this subject until the present time. Hinman and Lee-Brown state that Gigon (1856) was the first to observe pyelovenous backflow in cadavers and living animals. 2 During my activities at the anatomical institute of the University of Vienna, I observed for the first time the pyelovenous backflow in macerated kidney pelves. On inquiry, my colleagues informed me that this backflow made it difficult to demonstrate good kidney preparations. Similar findings are presented by Henle in Henle's Anatomy, 1866.

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(I could find no older report either.) Gigon came to the conclusion that the overflow of fluid from the kidney pelvis into the venous system takes place through venous plexuses, which surround the calyces. In 1863 Zaworykin and Ludwig (2) found that an overflow may take place easily into the venous system through a small rupture of the mucous membrane of the kidney pelvis. These observations appear to have been forgotten, because Poirier (3) said in 1891 at the meeting of the Societe de Biologie in Paris: uon several occasions during the injection of the ureter (human cadavers), the injected substance was observed to escape by the renal vein, although the operation was performed without any violence whatsoever." It was further reported that these experiments were repeated on chloroformed dogs with identical results. The meeting was closed with the following words: ''These facts are so strange that they are stated without any explanation," In 1893 Tullier injected a strychnine solution directly into the kidney pelvis of living dogs and found that death followed only if the ureter had been previously ligated, and then that a certain pressure of the pelvic contents was necessary for resorption in the kidney pelvis. Similar experiments were made two years later by Huber (Paris) although resorption through the veins was not observed. The first experimental work in German literature occurs in 1897. The observation of this questionable phenomenon seems to have caused considerable astonishment, similar to that at the Paris meeting. Lewin and Goldschmidt in Berlin, who for some time had been performing experiments on the vesico-ureteral backflow in animals, reported in a paper entitled uA Short Pathology" (4) that: '·When we wished to repeat this experiment (the inflation by air of the urinary bladder of a narcotized rabbit) on March 18, 1897, and filled the bladder with a small amount of air, the air penetrated the ureter just as the fluid had in our earlier experiments." ''The kidney was strikingly enlarged and engorged, the vessels of the capsule were filled with blood. Now we suddenly saw how the freely exposed vena cava was slowly being freed of blood, starting from below gradually extending above, A great many air bubbles could be seen in the blood through the

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vessel walls. The stream of air-filled blood then rose slowly upwards to the diaphragm. The vein became completely transparent and death of the animal ensued."a For our purpose it is more practical to pass over other chronological data and now to consider the more important points regarding pyelovenous backflow, accumulated by different authors through various animal experiments. The following points may be emphasized: 1. What is the fate of a fluid (gas) forced under pressure into the kidney pelvis through the ureter? Lewin (5), working on narcotized rabbits in which he forced a suspension of ultramarine and diatoms (as well as air) into the ureter from the bladder, came to the following conclusions: "There are 3 very small canal systems to be considered as exposed to a centrally directed pressure; namely the uriniferous tubules, the lymph spaces and the blood vessels." He found the above mentioned structures nearly always filled with the injected mass, but not to the same extent: "The microscopical examination showed the lymph spaces to be mostly filled; the perivascular lymph spaces were filled as much as the peritubular. The veins were filled with coloring matter to the same degree as seen in microscopic examination of cross sections." According to Lewin the uriniferous tubules possessed only one-third the capacity for the injected fluid. Marcus (6) repeated these experiments of Lewin and came to the same conclusions, namely that the uriniferous tubules were sometimes filled, but the venules and the lymph vessels more frequently so. There are greater differences, however, between Lewin and Marcus, concerning the mechanics of penetration, which we shall consider later. Keyes and Mason (7) obtained human kidneys at autopsy, which had been badly damaged by collargol pyelography and made the following observations: "The collargol is found within the tubules and glomeruli. Moreover, masses of collargol, small 3 This is a good explanation of the cause of death from an embolus following inflation of the bladder with air, several cases of which have been reported in the literature.

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and large, are found scattered between the tubules. The arteries and veins contain collargol." In the experiments on narcotized dogs, they never found collargol in the tubuli collingentes, but only in the blood vessels and lymph spaces and connective tissue "around the urinary canals." Blum, Oehlecker, and Tennant independently discovered after the work of Keyes and Mason that collargol injected into the kidney pelvis penetrated the interstitial connective tissue and lymph spaces, but that this only occurred through rupture of the uriniferous tubules. Hinman and Lee-Brown found after ureteral injection of the kidneys of dead sheep and rabbits that the collecting tubules were seldom and incompletely filled. They roentgenographed, and observed means of the fluoroscope the kidneys of living and dead rabbits as well as of many other animals, by injecting a fluid impermeable to the x-ray. On the other hand, Bird and Moise, using living dogs, proved by autopsy that the fluid penetrates the uriniferous tubules but not the venous system. They did not use the x-ray. To sum up the question concerning the fate of a mass injected under pressure into the kidney it may be said that: the injected fluid is found in all the tissue elements of the kidney, mostly in the lymph spaces and blood vessels, especially the veins, and least in the uriniferous tubules. These same conditions have been found in human kidneys subjected to collargol pyelography. 2. The question now arises: What is the mechanism of the passage of fluid from the kidney pelvis into veins, as well as into the lymph vessels and uriniferous tubules? And, what route does the fluid follow in the case of penetration of the venous system? Regarding these points different views are held. Lewin reports his view of such a n1echanism as follows: "It seems to me that the primary entrance of the foreign substance of the kidney pelvis is not into the vessels, but more the uriniferous (filled directly from the papillae) or the lymph vessels. the latter way seems the more plausible." ''It seems to me that pathological pressures, coming from the kidney pelvis, have their effect on the stomata of the lymph channels as well as on the penetrating mass. And that the pres-

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sure causes penetration of the vessels more than the effect of permeability itself." Lewin believes in the existence of a natural communication between the upper urinary tract and the circulatory system, and refuses to recognize any so-called traumatic communication resulting from tearing or bursting of the pelvis. Marcus has shown that Lewin's views are fallacious. By repeating Lewin's experiments he was able to confirm the passage of dye material from the pelvis to the venous system, but he found in a series of kidney sections: that whenever pyelovenous backflow was present, rupture of the kidney pelvis was also present and clear communication was evident between the ruptured pelvis and a neighboring ruptured vein. While Lewin believed his experiments explained general infection in the urinary tract, Marcus wrongly opposed him, for it is not so much how the backflow takes place, as the fact that it really does occur. Hinman and Lee-Brown found a direct passage of fluid from the pelvis into the venous system, similarly to Marcus: "At the apex of a minor calyx the large venulae rectae are superficially placed and it is at the base of the pyramids in such an apex that the opening into these veins commonly occurs. At minimal pressures small openings are more frequent at one or both poles, but at secretory pressure innumerable points of communication are probable. This pyelovenous communication . . . . is due to a structural condition at the base of the pyramids, where the rich plexuses of the venulae rectae are in close apposition to the deep sulci of the minor calyces. Pelvic distention spreads open these sulci and the pelvic contents pass into the venous capillary network beneath. . . . . " Hinman and Lee-Brown again agree with Marcus in that they also found that bursting of the pelvis caused a direct communication between pelvis and venous system. These authors compare the pyelovenous backflow to resorption of the aqueous humor of the eye: "The backflow of the fluid contents of the anterior chamber of the eye into the rich venous plexus of the sclera is analogous anatomically.'' Bird and Moise have not personally observed the backflow, but they succeeded in forcing fluid from the kidney pelvis into

PYELOVENOUS BACKFLOW IN HUMAN KID_i'\EY

the uriniferous tubules by gradual increase of pressure. make the following deduction (unproved): uif a backflow pelvic contents into the venous system of a living animal ever occurs, the probable mechanism is by rupture of tubules into the large straight and arcuate veins, related to them."

FIG. 1

The possibility of the last mentioned opinion cannot be abso-lutely rejected, but there is not anatomical proof of the same. Neither is there anatomical proof of the opinion of Lewin that there exists a natural communication between pelvis and renal veins. The pelvic ' 1lymph stomata" Lewin are not found anatomical literature. Therefore we have only for consideration the exact anatomical experimentation of Marcus and Hinman

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d

C

e

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Fro. 2

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Lee-Brown: These authors came to the same conclusion. namely that in animal experiments, a rupture of the kidney pelvis is necessary for pyelovenous backflow, a rupture that produces a more or less direct communication between the lumen of the pelvis and a neighboring vein. The author's experiments (in conjunction ·with Burger) on narcotized rabbits are reported elsewhere (8). The whole course of air inflation of the kidney pelvis makes it apparent that pelvis must be ruptured before air can pass into the venous system. This explains the sudden fall in pressure ')f the kidney pelvis, which occurs immediately before the appearance of air bubbles in the vena cava, as well as the soft hissing noise which is always simultaneously heard. Autopsy findings on our animals indicate that neither slow diffusion, nor transference of fluid by a long complicated way occurs. The autopsy showed: that the left kidney and also the liver were of air-cushioned consistency; on sectioning the liYer foamy blood exuded from the veins. The most important fact was that the passage of air from pelvis to veins did not take place slowly but suddenly and explosively. The anatomical proof of this lies in the air-filled blood in the frver veins. This may be explained by the fact that the air rapidly entering the vena cava displaces the blood and causes an air embolus in the liver veins. Summing up the experimental and anatomical findings concerning the mechanism and route of pyelovenous backflow, it may be that this is accomplished by direct communication between the pelvis and venous system, initiated by rupture of the kidney pelvis. The other explanation, such as that of Bird and is hypothetical, and may be possible, although not proven. third question concerns the pressure necessary to pro3. duce pyelovenous backflow. In some of Lewin's experiments, the dye solution was introduced into the bladder under pressure by a catheter or laparotomy, thus causing a backflow in the kidney pelvis. experiments were carried out so that after filling the bladder, the penis was ligated, thereby producing retention for many hours:

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in the second case a pyelovenous backflow was demonstrable. Prevention of the fluid from leaving the urethra was sufficient to produce a backflow. Such facts induced Lewin to argue that C

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Fm. 3

there must be a natural communication between the pelvis and veins and not a traumatic one as produced by rupture of the pelvis.

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On the other hand Marcus proved that the injection pressure was extraordinarily low in the case of a pelvic rupture: "It was striking what low pressure was necessary to cause rupture of the kidney pelvis, even in large dogs." Hinman and Lee-Brown were the first who measured the pressure necessary to produce a backflow in the kidney pelvis. In the kidneys of dead sheep, an

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initial backflow was obtained at 30 mm. Hg, complete filling of the veins occurred at 40 mm. Hg. Experimenting on living sheep, a partial pressure of 56 mm. Hg was obtained. When the pressure was registered on the manometer attached to the ureter, the fluid was injected into the same ureter under a measured pressure: backflow occurred at a pressure of 35 to 40 mm. Hg. An experiment on a live dog gave identical results: "These THE JOURNAL OF UROLOGY, VOL. XXIII, NO.

2

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experiments demonstrate pyelovenous backflow in the living animal at intrapelvic pressures, well below the renal secretory pressure." It is of special interest that the pressure necessary to produce a backflow was the same for living animals as for kidneys of dead animals. Burger and Fuchs found in both living and dead rabbits that a pressure of 60 to 115 mm. Hg was necessary to force air from the kidney pelvis into the veins. It thus appears that there are certain individual differences in the amount of pressure. As we have set forth in our publication, the actual pressure in the kidney pelvis is without doubt less than the manometer reading. This may be explained by the fact that Pravaz cannula, connected to the ureter, hinders the equalization of pressure by a sort of capillary action. This we can prove by models. The question as to the pressure necessary to produce pyelovenous backflow may be answered in the following way: The amount of pressure is exceptionally small according to all investigators. In some experiments a backflow was produced without artificial aid by producing an internal pressure due to retention of the urine (9). No other factors were necessary to produce this condition. No difference was found in the required pressure between cadaverous and living organs. II. THE AUTHOR'S INVESTIGATIONS ON THE KIDNEYS OF HUMAN CADAVERS

It seems advisable at first to ascertain if the intrarenal topography and mechanical relationships are the same for the kidneys of mammals (sheep, rabbit, dog, rat) as for the human. Also if the previously reached conclusions apply to human pathology. As a matter of fact the anatomical details of the internal topography show essential differences; in the contrast to the well known form of the human kidney pelvis, the animal pelves belong to the type of leaf-shaped pelvis (Hyrtl). The interlobar arteries and veins run in deep grooves in the pelvic walls. At first sight the vessels appear to be in very close relationship to the pelvic walls. In spite of these differences between human and animal kidneys, there are important analogies in the pyelovascular mechanism:

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Hinman and Morison (10) have shown in rabbit kidneys how an increasing hydronephrotic enlargement of the pelvis leads to a progressive compression of the vessels emptying into the renal sinus. I could show the same thing for veins in the human kidney (11): If a fluid is injected into the kidney under increasing pressure, then the veins in the region of the calyces are not well filled. Increasing expansion of the calyces by urine retention might also affect the circulation of the neighboring veins in vivo. In the course of further experiments Hinman and Morison (12) injected human hydronephroses with the same results: "In hydronephrosis the circulatory changes are produced by mechanical displacement acting by compression or stretching according to the course of the vessels." Investigators are probably unani-mous regarding the question of compression of the vessels by the increase of pressure in the pelvis. It may be deduced from the Hinman, Lee-Brown investigation that these authors found the place of backflow to be at the apex of a minor calyx, which according to the Hyrtl nomenclature is called the fornix calicis in the human kidney. By means of a macerated preparation, I have shown clearly the relation between the fornix calicis and the venous plexus of the renal sinus. And I wish now to refer to this previous publication. 4 The veins lie very close to the fornix calicis and they are not separated by any fatty connective tissue, They lie parallel to the axis of the pyramid and touch the fornix calicis in a straight line tangentially, The veins also cross the axis of the pyramid in order to reach their columns of Bertini and cover half the circumference of the fornix. The interlobar veins of the anterior as well as posterior portions have short but numerous anastomoses with each other immediately before their entrance into the parenchyrna. Such anastomoses also connect the veins of the anterior with those 'Figures 1, 2 and 3 were obtained from the material on which I carried out my investigation "The Internal Topography of the Kidney" (Zeitschrift f. urol. Chir, (18), 3/4, 1924) at the Anatomy Institute of the University of Vienna, where the pyelovenous backflow was briefly considered. Of these, figure 2 is the only obtainable copy published, which to me is satisfactory in the light of the work that has been done since these observations.

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of the posterior area before their entrance in the organ. ::VIoreover these anastomosing branches frequently have the same close relation with the fornix calicis as was described. Threefourths the circumference of the fornix calicis is of ten surrounded by a venous plexus (this is particularly clear in figure 1), whose individual trunks for the most part have the caliber of the interlobar veins, lying in the walls of the calyx. It is clear from figure 1 that the venous circulation in the calyx must sustain considerable injury in event of expansion of the calyx. In any case it may be said with certainty: The human renal veins do not exist in that close, flat relation with the pelvis, as is the case with the leaf-shaped renal veins in animals, which are sunk in grooves. Still, the fornices calices are the definite places for pyelovenous backflow and show a close relation to all pyelovenous phenomena, so that the anatomical basis for certain functional conditions appears centered here and the mammalian kidney is in no way inferior for this purpose. It is well known, since the experiences of Hyrtl in corrosion anatomy,, that increasing pressure in the case of fluid injections into the ureter and kidney pelvis results in extravasation, and the first place for the fluid to leave is a fornix calicis. The mechanical proof of this fact should lie, as I could show, in the fact that the kidney pelvis is regarded as the strongest ductile segment of the upper urinary passages. The kidney parenchyma lacks an extensive ductility. It is then apparent that the line of separation between the weak and strong parts of the pelvic ca-vity is at the point of insertion of the calyx in the kidney paranchyma (at the figures of the fornix calicis). This is the place of predilection for a continuous break in the case of internal pressure. How does the extravasation occur in this so-called place of predilection? In the greater majority of cases, the fluid injected into the ureter streams into the renal veins due to sudden loss of tension in the wall of the pelvis. In rarer cases a subcapsular extravasation corresponding to the convexity of the kidney occurs. Every so often it happens that the fluid is visible in the renal sinus, thus again illustrating a closer relationship of the vessels to the parenchyma. In both the last mentioned cases, the

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extravasation is the result of sudden loss of tension of the pelYis. Sometimes two or eyen three of the well known possibilities of extravasation may occur, the most frequent being a combination of subcapsular extravasation with a rupture in the venous system. I find that arteriosclerotic or chronic inflammatory shrunken kidneys show no variation from the conditions described for the normal fresh cadaver kidney. In greater degrees of parenchymatous and fatty degeneration; the extravasation was more frequently directly into the fatty tissue of the renal sinus. I was unable to find any correlation between the relative frequency of individual types of extravasation and the anatomical configuration of the renal pelvis. For the purpose of observing the conditions of rupture of the venous system from injected fluid, I injected into normal human kidneys of different ages and as fresh as possible, 20 per cent sodium bromide solution with the aid of a recorder attached to the ureter. The following obse1Tations were made with the fluoroscope: vVith a gradual increase in pressure there comes a general expansion of the pelvis, the calyces becoming plumper. This is followed by a flattening of the papillary tips. For a moment the syringe-plunger yields considerably and further injection results in much less expansion. At the same time cord-like shadows appear immediately in the parenchyma at the point of the small calyces. These shadows lengthen very rapidly, at the same time narrowing, and soon communicate with each other by bow--shaped arcades, from which further branches leave, so that the vessels appearing are recognized as the veins lying in the parenchyma. The filling of the veins does not occur simultaneously throughout the pelvis; a constant precedence of definite groups of calices could not be demonstrated. The most important observation is that different stages of described pyelovenous backflows could be demonstrated through a single application of the roentgen ray. In further injections, pictures appeared, which were obtained by radioscopy of another kidney. ·while the vessels of the upper pole of the kidney appeared as sharp, contoured lines, the Yessel contour gradually disappeared, although the bow-shaped course

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of the vessels in the last mentioned place was still recognizable. The effacing of the contour advances so that finally strand-like shadows appear in the parenchyma under the capsule. I advanced the view in my first publication, that this r'bunched" appearance of the contrast fluid in the parenchyma resulted apparently through the papillary duct. I must, however, withdraw this original interpretation; I found (as shown above) that the shadowing in the parenchyma was introduced by a haziness of the vein contours, so that thereby further parenchymal infiltration appeared to cqme from the veins (as was shown). I shall return to this point later. Corrosion methods offered another method for the study of pyelovenous backflow: celluloid dissolved in acetone was injected into the ureter by means of the customary Teichmann syringe for anatomical injections. This was done until the injected mass appeared at the stump of the renal vein. After congelation of the mass, it was corroded in dilute hydrochloric acid. The small calyces show greater or smaller horn-shaped outgrowths, which extend from the fornix calicis. Several of these horn-like extravasations proceed to the places which are identified as veins. These places have been filled peripherally as well as centrally toward the stem of the renal vein. It is worthy of special attention, that by the most painstaking examination with the lens, no relation could be shown between the veins injected in the pyelovenous backflow with the kidney pelvis, so that it is hereby shown to be true that the veins are filled from an extravasation from the fornices calices. To summarize then the observations made with the x-ray, as well as by the corrosion method: 1. Pyelovenous backflow in human cadaver kidneys occurs. 2. The place and mechanics of the point of exit of the fluid was shown in the gross. After the present investigation, it was not at all clear to me whether the fluid which left the pelvis at the fornix calcicis, actually entered the surrounding vein stems, and still much less clear why this should be the case. The following investigation was devoted to a study of the finer mechanics. It was thought that a special condition, a specific vulnerability

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based on peculiarities of structure, might be the cause of this puzzling process. Tinner (13), in the discussion of my first oral presentation on the pyelovenous backflow, made the statement: "I do not believe that the neighborhood of the veins and of the neck of the calyx is the cause alone, I believe more that it is a peculiar condition of the wall of the intrarenal veins." I set about to investigate this problem in connection with my clinical colleague, Dr. Erwin Risak. On account of perfectly negative results, we have not published the results. However, it appeared nece~sary to reopen this problem and so with the friendly agreement of Dr. Risak, it is as follows: Vve examined fifteen human kidneys, which were for the greater part obtained from operation material from Hochenegg's clinic. The suspected parts were removed from the kidneys, :fixed in formalin and the sections stained with hematoxylin-eosin and with Weigert' s elastic fiber stain. Normal kidneys were examined, as well as cases of pyelonephritis, pyonephrosis, hydronephrosis, tuberculosis and hypernephroma. The veins of all caliber, in the renal sinus as well as the parenchyma, showed not the least structural anomaly. The thickness of the wall and their content of elastic fibers correspond(s)d throughout to the caliber, No difference in the wall structure of similar veins in the other organs could be found. In single sections, we found large venous trunks lying directly on the fornices calices, as would be expected from the corrosion preparations. We saw more frequently, however, that the veins of the wall of the calyx were separated by a layer of fatty or connective tissue 2 to 3 mm. in thickness. Since the corrosion preparations showed the pelvis and veins in maximal dilation, it might be objected that this thin layer was brought about by pressure in the hollow spaces and is not of any value. We could find no basis, after histological examination of the veins, that offers an explanation of why the extravasation from the pelvis breaks into the venous system with predilection. The first hint of the answer to this question struck me while examining the corrosion preparations, in which the kidney pelvis and the renal veins were injected separately. These preparations were obtained in the same way as that in :figure l. In cases where

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the venous injection was successful, but the pressure abnormal, the frequently described extravasation occurred at the fornices calices. This extravasation showed peculiar, informative conditions about the venous system filled directly from the trunk of the vena renales. Although the extravasation at the fornix calicis poured into the renal sinus, that extravasation frequently showed special conditions, which rested in such places in the fornix calicis. In these places, a larger vein, tangent to the calyx, emerged from the sinus in the kidney parenchyma. Instead of the solid horn-shaped formations, I found semicylindrical formations, which, leaving the fornix calicis, surrounded half the circumference of the veins. These formations often went deep into the parenchyma, retaining these conditions. In each case they reached almost to the vertex of those venous arches; which arched over the base of the pyramids to the border line of the cortex. Such extravasations of the kidney pelvis corresponded with the vein trunk (interlobar), which they ensheathed in places. But they were generally separated themselves from the venous effusion by a space of 1 mm., which corresponds to the wall of the vein destroyed by the corrosion. If different dyes were used as injection masses for tltte venous system and for the pelvis, then the extravasation ensheathing the veins showed a combination of both colors. The above discussed, half-cylindrical, sheath-like extravasations investing the veins are well illustrated in the upper calyx where rupture and extravasation resulted from increased pressure. The extravasation almost reached the vertex of the venous arches, that is the edge of the cortex. At those places where the edge of the calyx is not in close relationship in the neighboring veins, the horn-like extravasations may be seen in the sinus. Another specimen shows an isolated calyx with extravasations. (Corrosion preparation, viewed from the cortex along the pyramidal axis.) Several extravasations exist along the circumference of the fornix. The extravasations take on a different appearance where they come in contact with an interlobar vein. They form small walls on each side of the vessel, which go between the veins and thus constitute the venous investment described above. All

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possible intermediate stages are found among suitable corrosion preparations, from the initial ensheathment of the vessels to more advanced stages as a result of extravasation from the kidney pelvis. 5 I will consider next the character of these clefts which gi\·e rise to the perivenous, shell-like extravasations in the c01Tos10n

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.FIG. 5

preparations. It might be supposed a priori that perivenous lymph spaces existed here similar to the perirnscular lymph spaces of the central nervous system. Very exact anatomical investigations of the lymph channels of the renal parenchyma have been made. Stahr (14) came to the following conclusion regarding this question: "The blood vessels, often accompanied by lymph channels, do not appear ensheathed any,vhere." 5 Since only the veins are of interest in pyelovenous backflow, I have omitted conditions regarding the arteries. Although I have sometimes seen sheath-like extravasations around arteries, also.

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Kumita (15), who continued the investigations of Stahr in more detail, offers the following conception of the lymph channels of the medullary substance: "The lymph capillaries empty into rather large lymph vessels. These ascend between the uriniferous tubules and open into the channels running between the medullary substance and the cortex. They run along with the vasa arciformia to the hilus." However, the present problem is not concerned with the lymph spaces ensheathing the vessels. Furthermore, the illustrations of Kumita fail to make the existence of such clear. An observation of Disses (16) shows that the questionable intraparenchymal clefts brought about in the corrosion preparations are not a question of preformed spaces: "The veins will be kept patent by strong adhesions of their walls with the kidney substance." Since the adventitia of the veins is directly adherent to the parenchyma, a perivenous space is not normally present. The observations of Disses concerning the connective tissue stroma of the kidney isolated by pancreatic digestion is of interest: "The uriniferous canals are not only completely united with the vessels and capillary plexuses so that they are surrounded by a common capsule, but there is also a special intervening tissue, a stroma, binding the capillaries and uriniferous canals together, and also enclosing the larger vessels, the nerves and lymph channels. All branches of the vessels, as well as the uriniferous canals, are lodged in the interstices of the stroma, which is in relation with the mucous membrane of the renal pelvis at the papillae. The network spreads out from the adventitia of the larger vessels, forming strong bands, between which the finer fibers of the network are connected." I have investigated these conditions by examining numerous kidneys-fresh as well as those fixed in formalin. If a kidney is split in any direction to the hilus and a part of the fatty tissue in the sinus renalis between the vessels and calyces removed, the point of entrance of the interlobar veins into the parenchyma (directly in the Columnae Bertini between the pyramids) may be easily seen. It is found that the venous trunks are imbedded in corresponding half-cylindrical grooves in the parenchyma, to

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the sides of which the Yessel wall itself is fastened. Proceeding from its point of entrance, the vein wall may be easily removed from the parenchyma by rupturing delicate strands of connective tissue with a probe. A cylindrical perivenous space, not preformed but artificial, in open communication with the sinus renales is opened up. If one now proceeds carefully with the re-

FIG. 6

moval of the vein wall to the cortex, its removal is found to-be more difficult near the periphery. In the first place the wall of the vein becomes more delicate as it extends peripherally and divides and subdivides so that in most cases it frequently tears at the line of junction between the medullary and cortical areas, no matter how careful the dissection is. In the second place difficulties are encountered at points where small venules leave the

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parenchyma and empty into the interlobar veins. The wall of the vein is more adherent to the parenchyma at these places. In the case of too much roughness in dissection the small vessels emerging from the parenchyma that traverse the artificial perivenous space in order to empty into the interlobar vein are already strained to thebreaking point just before the rupture results. Let us now attempt to visualize the mechanism of pyelovenous backflow in human kidneys in the light of the above mentioned findings: Rupture in the kidney pelvis due to increased pressure occms at the fornix calicis because the latter represents the angle of maximal and minimal extensibility. The fluid remaining in the pelvis under pressure is forced into the sinus renales and also between the parenchyma and fatty tissue of the sinus. Diffusion in the sinus-fat due to its incompressibility results in a certain resistance, so that conditions arise for the diffusion of the fluid at the point of least resistance. Such a point is present. The connective tissue stroma of the kidney is connected with the mucous membrane of the pelvis on the one hand and with the adventitia of the entering vessels on the other. A gap is torn in this connective tissue as a result of the rupture of the pelvic wall, and is filled with the fluid. Now since vessels entering the parenchyma so frequently lie in immediate proximity to the calyx, the fluid could penetrate between vessel and parenchyma, provided the tissue fastening the vessels to the parenchyma is torn. The perivascular space above described is artificially produced in this ·way, and fluid is forced along it towards the cortex under persistent pressure. This abrupt rupture in the neighborhood of veins causes injury of their walls and also rupture of the small venules leaving the parenchyma. Now the way is open for further spread of the extravasated fluid. The route of pyelovenous backflow into the lumen of the vein itself is completed by these lesions of their walls. Let us consider for a moment the character of the pyelovenous backflow modified by the following factors: If the subsequent outflow of fluid from the pelvis ceases completely after establishment of the backflow, then the infiltrated contents of the perivenous spaces will drain off in the veins, and immediately flow into

PYELOVENOUS BACKFLOW I'.\' ffl'MAN KIDNEY

the richly anastomosing venous nets of the kidne:v and expand them. The blood stream then becomes the regulating factor in drainage. If the rate of outflow from the pelvis is moderate, then the pelvic communication through the perivenous space is established with the veins and a compensating equilibrium of inflow into the blood stream occurs. vVhat happens, however) if more fluid flows into the perivenous space from the ruptured pelvis than the veins can carry off'? There must then an

--- a Vene

Fie;. 7

overflow the perivenous spaces. The fluid must pour into the perivenous spaces of the collateral branches of the interlobar veins, and infiltrate throughout the parenchyma probably in this way. A careful review of the observations made by x-ray and described confirms this assumption. It was stated on after rupture of the pelvis streak-like shadows page 445 appeared at the fornices calices. The filling of the narrow and sharply contoured veins precedes the somewhat broader and blunter shadows. We believe we are justified in identifying

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these initial shadow-streaks as the perivenous spaces primarily filled. We further believe that the vessel contours gradually disappear under further injection into the pelvis. This is interpreted as meaning that the contents of the perivenous spaces cannot be drained off fast enough so that these over-filled spaces themselves become identified as the "obliterated vessel contours." Our assumption further agrees with what we stated on page 447: "That further parenchymal infiltration appears to come from the filled vessels (as shown by the x-ray)." Because of the above considerations it might be more precise to say: "From the overflowing perivenous spaces," as soon as these can no longer be drained off through the veins on account of their too rapid overfilling. As to how the conditions mentioned on page 444 about the pyelovenous backflow concern other extravasations from the kidney pelvis which are apparent in the hilus renalis~subcapsular for example~it can be justly stated that all observations indicate that every extravasation from the kidney pelvis is from the sinus renalis. 6 Regarding other extravasations from here, it is a question whether they may not occur from some point on the circumference of the calyx, in the neighborhood of which vessels may be found entering the parenchyma. If such is the case, the fluid then infiltrates the corresponding perivascular space, and can thus reach the border line of the medullary substance and cortex. If a lesion of the wall of the veins occurs at this location, the pyelovenous backflow is at once established. If such a rupture does not occur, which is certainly a possibility, the extravasation then makes its way for the most part beneath the capsule. It is not surprising, therefore, if it spreads further towards the capsule in the perivenous spaces of the branches of the venous arches lying between the medulla and the cortex and finally appears as a subcapsular extravasation on the surface. If the primary pelvic extravasation occurs at a place in the calyx which lacks the intimate relationship with the interlobar vessels, then the extravasation permeates the sinus-fat in order 6 For the direct infiltration of the pelvic content in the collecting tubules, see Section III of this paper.

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to appear in the hilus renalis. The frequency ratio for pyelovenous backflow, subcapsular extravasation, sinus-hilus extravasation is about 70: 15: 15 for fresh, normal human kidneys. I must now undertake certain corrections of statements made in my first work-(Investigations of the internal topography of the kidney). I expressed the view that the reverse of pyelovenous backflow could occur with equal facility; this must be changed on the basis of experiences since met with. If pyelovenous backflow has been once established in a kidney and then fluid is directly injected into the renal vein, occasionally it will flow into the pelvis by the route already prepared by the backflow, but not always. It must be supposed that the filled vein, tense from direct injection, lies in the wall of its parenchymal canal, from which it was displaced by the beginning backflow and that an automatic plugging of the vein lesion may occur in this way. If a fresh, intact, kidney is injected with fluid directly into the vein, direct rupture into the pelvis is observed only in very isolated cases. I only observed this (and not regularly either) when a thick viscous injection-mass like celloidin acetone solution or Teichmann's substance was used. I could find nothing certain about the place and mechanism of this reverse backflow from the vein into the pelvis due to its variability. In concluding this report it seems appropriate to mention the pressure under which rupture occurred in typical places in the renal pelvis, with or without pyelovenous backflow. For fresh kidneys it varied between 60 to 120 mm. Hg, and in several instances it was somewhat above or below this. III. CONCLUSIONS FOR HUMAN PATHOLOGY AND CLINIC

It appears advisable to compare the results that have been obtained for human kidneys with the results of pyelovenous backflow in experimental animals, so far as they can be of any certain value. The question at once arises whether fluid from the human kidney pelvis can infiltrate the perivascular spaces and veins in any other way than that shown, as for instance: directly into the papillary duct openings of the papillae? As set forth, such infiltration was observed secondary to pyelovenous backflow in animal experiments.

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As has been stated, several authors have observed the penetration of collargol in this way in human kidneys. I have performed several experiments for the purpose of observing this, and was unable to do so. I have not followed the question further, namely whether fluid penetrates the papillary ducts in kidneys wherein pyelovenous backflow was observed, and I believe on the basis of my own observations: that it is not easy in any case to force substances from the pelvis into the urinary canals. According to Hinman's and Lee-Brown's experiments on animal kidneys the oblique openings of the ductuli on the surface of the papillae (forming a sort of valve mechanism) might function similarly in the human kidney as well. Nevertheless it appears from individual experiments by other authors that such penetration can take place from pyelovenous backflow. 7 That it is rare and attains no high degree of occurrence, probably lies in its causative factornamely that it appears to require considerably higher pressure. Now it is presumed that by extremely gradual increase of the pelvic pressure, the necessary pressure to produce pyelovenous backflow without pelvic rupture will be reached. The latter appears to occur only if the pressure has not reached the height necessary for direct penetration. Moreover, the type of fluid injected cannot be entirely disregarded. With very dense, viscous substances like celluloidacetone solution, the pyelovenous backflow is promptly produced; on the contrary it must appear impossible a priori for this oily mass to penetrate the narrow urinary canals. Sigl (17) has shown that a certain difference exists between crystalline salt solutions and colloidal solution (i.e. collargol) : the surface 7 Pyelovenous backflow at the time of pyelography, Surg., Gynecol. and Obstet., 592-600, May, 1927. "In conclusion, it may be definitely stated that pyelovenous backflow frequently occurs at the time of pyelography and that tubular backflow for a short distance into the papillary ducts also occurs. In the case of pyelovenous backflow, radiation into the cortex first appears as a cone or funnel deformity from the base of pyramids, and if back pressure is sufficient may later show the arching from filled anastomotic venous arches. Radiation into the cortex then appears along the interlobular veins, a picture that never occurs with tubular backflow in which there is a short brush-like radiation from the tip of the papilla into the medulla for a short distance. Such pyelovenous and papillary backflow when unrecognized may lead to errors in interpretation of pyelograms."

PYELOVENOUS BACKFLOW IN HUMAN KIDNEY

tension of the latter is considerably reduced due to colloidal nature, thus under low pressure it cannot penetrate capillary tubes~even the uriniferous tubules. It may be pointed out that when halogen solutions (i.e. sodium bromide) are used, direct penetration into the uriniferous tubules is less liable to occur and with less volume, than pyelovenous backflow, while with colloidnl suspensions used previous to or simultaneous with the backflow, the uriniferous tubules may be filled through direct penetration. 8 It was stated that the way pyelovenous backflow occurs is that in animals a direct communication is established between peh'is and capillary-plexus and, according to Hinman and Lee-Brown. rupture of the pelvis at the edge of the calyx. There is a difference in so far as the intermediate limb of the perivascular spaces shown in human kidneys was not observed in animals. It is possible that the lymph spaces which Lewin spoke of as a means of communication between the veins and the pelvis were not preformed lymph spaces, but artificial clefts due to extravasation through openings. An exact statement cannot be made at this time whether pyelovenous backflow occurs by the same mechanism in kidneys as in animals. It is of extraordinary interest that in the animal experiments of Hinman and Lee-Brown the pressure necessary for backflow was less than the secretion pressure of the kidney concerned. This is probably explained by the apparatus used by these authors: the manometer; from which the secretion pressure was read, was fastened to the ureter, so that the manometer pressure not only indicated the true secretion pressure of the kidney, but also the pressure produced by musculature of the ureter. Thus a higher pressure value was produced than was actually present in the renal pelvis. For reason we must not consider these experiments as absolutely conclusive of the possibility of a pyelovenous backflow of the pelvic contents occurring when there is free passage of urine through the ureter under the physiological conditions of life. The state of affairs in actual retention is entirely different. The degree of pressure existing in those sections of 8 It might be mentioned that I could produce backflow in the human kidney as well with celluloid solution and sodium bromide as with air and collargol.

THE JOUHNAL OJ.i' UROLOGY, VOL, XXIH, NO.

2

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the upper urinary tract lying between the kidney and the obstacle to passage is unknown. The experiments of Lewin and also Marcus show that these pressures are sufficient to produce, almost spontaneously, pyelovenous backflow without manual and instrumental aid. 9 The question now arises, whether the human organism, as well as the animal, may spontaneously produce corresponding pressure values in the upper urinary passages'? This single important fact may now be considered. Dilatation-pain plays an important role in the execution of pyelography. If "contrast" fluid is injected into the pelvis through a ureteral catheter and the patient feels a "certain tension-a slight sharp pain around the kidney," it means that the pressure in the kidney pelvis has reached a certain height. Whether the subjective sensations of the patient are produced by the expansion of the pelvic wall or whether they are an expression of the muscle contractions, we do not know, but that is not important. It is well known that pain occurs when a muscular, hollow organ attempts to discharge its contents against a certain resistance. In the region of the intestinal canal the internal pressure in the "rigid loop" is palpatorily manifest. The following viewpoint is tenable for the upper urinary passages: The slightly painful sensations in pyelographic filling of the renal pelvis and the severe pain of renal colic are the result of different intensities of one and the same process: an increase of the pelvic pressure with distention of the walls with relation to the reflex loosening of muscle contractions. It is certainly not justifiable to consider the intensity of the accompanying pain as a direct indicator of the increased pressure; it must be taken into con~ sideration that between pressure and distention on the one hand and pain on the other, certain proportional conditions exist and that the pressures occurring in the pelvis in severe renal colic are actually higher than those which are obtained by careful instrumental filling. Apart from the renal pelvis and ureteral musculature resisting 9 Special attention is called to the fact that the same pressures occur in pyelovenous backflow in animals in vivo as well as in fresh animal cadaver kidneys. These experiences should be tried on human kidneys.

PYELOVENOUS BACKFLOW IK HUMAX KID:\'EY

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an impediment, and the resulting congestion of the urine, following may contribute to pressure-changes: fluctuations of the intraperitoneal pressure, the vesico-ureteral backflow due to insufficiency of the sphincter at the ostium vesical of the ureter, and antiperistalsis of the ureters. The two last mentioned factors have received special attention recently. Nothing is knovvn up to the present time about the fluctuations in pressure in the kidney pelvis; time and methods are needed to actually determine this in human beings. After what has been said, there is one thing to be regarded as certain: that increases of pressure in the human kidney pelvis are no means rare and actually exceed those encountered in pyelography. The question is whether these higher pressures cause pyelovenous backf!o,Y. There are two ways by which we xnay show when pyelovenous backflow occurs in humans: (a) Direct obserrntion by pyelography; (b) the reaction of the organism to pressure increases in the kidney pelvis due to artificial or spontaneous causes. It is a priori improbable that the passage of the contrast fluid into the veins would be visible by pyelography or pyeloscopy or even that such a backflow actually occurs. As soon as a certain pressure and distention occur in the pelvis, the patient experiences pain, and further injections cease. If backflow does occur at the high point of the pressure increase, then this occurs through a minimal tin1e interval on account of a lack of rebound, since the fluid that enters the veins is carried away by the blood stream the direction of the backflow ,vould be short since the filled veins immediately close the openings. Probably only the preparatory and initial stages and not the backflmv itself are to be observed pyelographically; but considering great regularity with which backflow actually occurs in cadaver experiments, it is reasonable to assume that such is case 1n vivo. It is known that in pyelography of the normal kidney occasionally abnormal shadows occur about the pelYis during the normal course of things. The exact morphological study of these has induced me to consider them as initial stages in pyelm·enous backflow in every

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case. In a normally contoured pyelogram10 the point of the cranial calyx appears shadowed, although not in such a way that this shadowing could be of certain morphological significance. The abnormal conditions lie in the most caudal calyx. This shows, as well as both middle calyces, the cup-shape due to the injection

Fm. 8

Fm. 9

of the papillary points. A horn-shaped, curved, sharply bordered shadow appears at the caudal circumference of the edge of the calyx. The shape and position of this shadow conform with those formations found as extravasations of the fornix calicis in the 10 This, as well as the following pyelograms taken with 20 per cent sodium bromide solution, was taken without any disturbing factor occurring during the pyeloisraphy.

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corrosion preparations. We believe, on the basis of this similarity that the questionable protuberance of the most caudal calyx is an extravasation into the sinus renalis after rupture of the pelvis at the fornix of the lowest calyx. Another pyelograrn shows diffuse shadows at the most cranial and caudal calyces, which

Fm.IO

Frn.11

could be identified with the initial extraYasations and are to regarded as more extensive extravasations in the region of the sinus renalis. The middle calyces probably have sharp outcroppings, which correspond morphologically with the pointed extravasations. The course of the catheter is quite visible. It is worthy of mention that it does not end in that calyx which shows the shadows recognized as extravasations. Thus the extravasa-

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tion of the contrast fluid cannot be attributed to a traumatic lesion of the pelvis from the point of the catheter. Only a true rupture of the pelvis at the fornix calicis occurs as such, produced by the injection pressure and the distention of the pelvic wall. A third pyelogram shows two thick extravasations approximating one another, which are placed like horns on the edge of the uppermost calyx. Conditions are visible which I have found in very many pyelograms and should be regarded as the very beginning of an extravasation: the fornix calicis appears much more hollow on one side than the other, which, after what has been said, can be regarded as the initial loosening of the calyx wall from the kidney parenchyma. So the fact must be borne in mind, that in smoothly running pyelographies multiple pelvic ruptures often occur in typical places. The first stage of the pyelovenous backflow occurs when the injected fluid goes from the pelvis into the sinus renalis. Considering the great caution, with which pyelography is carried out today, it is not to be expected that the process of extravasation occurs frequently in the sense of a backflow. Necker (18) has very recently published a case which can hardly be regarded otherwise: "Pyelogram of the right kidney of woman aged fifty-five years was examined for a suspicious tumor. The first impression showed after injection of 3.5 ccm. umbrenal a kidney pelvis considerably broadened in the longitudinal and transverse diameters, from whose caudal calyx a sharp-edge, broadened shadow (a finger's width) could be traced to the surface of the kidney." During the pyelography, chill and the tendency to vomit occurred (as Dr. Necker stated during the demonstration); "Three minutes later roentgenograms taken during a refilling showed no trace of these shadows." Necker designates this finding as "artificial inhibition of the kidney tissue." Considering the rapid resorption of extravasation, I remarked in the discussion that it was probably a rupture into a vein, although the width (finger breadth) and lack of anastomosis appear to deny this conjecture to a certain degree. On the basis of previous experiences in the manner and mechanism of pyelovenous backflow, I believe I can advance the argu-

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ment that the finger-breadth streaks extending to the cortex, which disappeared completely after three minutes were perivascular spaces filled from a ruptured pelvis, consequently the second stage of pyelovenous backflow. The vein lesions, studied in the filling of perivenous spaces in cadaver kidneys, make possible the rapid outflow into the veins, while a complete resorption into the imbibed kidney, as Necker stated, could hardly occur in three minutes: thus a pyelovenous backflow had occurred and only the second stage was visible on the plate. I dispose of one of Necker's observations myself, because a second impression, which could have shown the rapid resorption was not taken. A fourth pyelogram shows a less sharp, bordered, cloudy shadow next to the most caudal calyx; which might come from the contrast fluid appearing in the sinus renalis. Further, a sharply bordered, dark band proceeds from the same point on the calyx circumference, which disappears towards the cortex along a light, bow-shaped course. The similarity between this shadowband and the initial pelvic extravasation is apparent. The veins are filled from the latter so that they could be considered as expression of the contrast filled perivenous spaces through comparison with the corrosion preparations. We believe we can say the same of the questionable shadows in this last pyelogram. The fact that a pelvic rupture from the small pressures of pyelography occurs as a preliminary condition to pyelovenous backflow, as well as the sound assumption that a backflow itself occurs, leads to the conclusion that this phenomenon must be dealt with in human pathology. As stated, it must be assumed that in spasm-like colic conditions of the upper urinary tract (corresponding to the greater intensity of pain), higher pressures actually occur in the pelvis, than in pyelography. All actual observations and occurrences described in the foregoing prove the (here, the only possible) assumption that a pyelovenous backflow of pelvic urine can actually occur in the course of and as a result of colic. A more important point lies in the manner in which the body reacts to a venous rupture from an infected pelvic content. The characteristic of the "uroseptic fever attack" with congestion and

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infection of the urinary tract is the sudden rise in temperature under rigor, as well as the almost immediate fall of the same, which is well known in the temperature curve of such patients and manifests itself by arising from a completely or almost normal temperature plane. Such a septic fever course always occurs from such organs-according to our present day knowledge it is regarded as an expression of the entrance of infectious materials from the tissues into the blood vessels. On one side the fact that fluid in the renal pelvis under pressure directly enters the veins with ease and predilection, and on the other the experience that congestion of infected urine leads to a "uroseptic attack," which occurs in the group of those events which will in general lead back to the entrance of the infected material into the blood stream, the following assumption appears to be well-founded: that the septic fever curve in the temperature course of patients with congestion and infection of the urinary passages should always be considered as the clinical expression of pyelovenous backflow waves. Hinman and Lee-Brown on the basis of their animal experiments attached great significance of pyelovenous backflow for the pathology of hydronephrosis. The point that in hydronephrosis with complete ureteral closure a functioning parenchyma is still found was explained by Cushny, Heidenhain and others, through the retrograde resorption of the secretion in different sections of the uriniferous tubules. Hinman and Lee-Brown believe they can substitute the pyelovenous backflow for these factors and found also in animal experiments that in increasing hydronephrotic atrophy of the kidney the pressure necessary to cause pyelovenous backflow was less. As to the question whether these assumptions can be applied to the human organ, nothing can be said at this time on the basis of our investigation of the human kidney. Hinman and Lee-Brown direct attention further to the points found by themselves in animal experiments and confirmed by us in the human kidney, that a pyelovenous backflow, once initiated, can prepare the way for a venous hemorrhage in the renal pelvis and they ascribed to this the pathogenesis of bleeding in inter-

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mittent hydronephrosis. This assumption can be approved on the basis of our considerations: if in the course of stone colic a renal hematuria occurs, it must not be thought that only the wall lesion in the ureter due to the stone is the source of the hemorrhage. The bleeding could also come from the point of rupture in the kidney pelvis, if a pyelovenous backflow occurred during the colic, or the bleeding could come from a vein itself that had been opened by the backflow, (opposite to the way of backftow). It may briefly be shown further that the conditions of the peri.vascular spaces described could act as guides to the renal pelvis and its contents in further investigations, not only for the importance of certain pyelographic findings (extravasations) but also in case of determining the by no means perfectly clear manner which an ascending infection breaks its way into the kidney parenchyma. Further, this work on pyelovenous backflow in human kidneys is a new memento to the utmost caution in the technique and procedure of pyelography as well as the choice of contrastsubstances. ll The whole result of the investigation might be regarded as a contribution to the question as to how illuminating anatomical and hydromechanical factors (which, as mentioned in the beginning, were stipulated embryologically in the latter line) can be to the surgical pathology of the human kidney . REFERENCES (l) HINMAN AND LEE-BROWN: Jour. Amer. Med. Assoc., lxxxii, 607-613, 1924. (2) ZAWORYKIN AND LUDWIG: Sitzungsbcr. der kaiser!. A.kaclemie cl. Wissenschaften, 1863. (3) Pornrnrn: Ann. des maladies gen. urin., 1891. (4) LEWIN AND GOLDSCHMIDT: A Short Pathology. Dtsch. med. \Vocht>nBchr., 38, 1897. (5) LEWIN: Arch. f. exp. Pathol. u. Pharmakol., 40, 1898. (6) MARCUS: \Vien. klin. 1Yochenschr., S. 725, 1903. ('1) KEYES AND MASON: Amer. Jour. Med. 144, 1915. (8) Wien. klin. \Vochenschr., Nr. 6, 1927. (9) HINMAN AND VECKI. Pyelovenous backflow. The fate of phenolsulphonephthalein in a normal renal pelvis with the ureter tied. Jour. Urol., xv, 267-271, 1926. 11 Concerning dangerous moments brought about by gas inflation of the renal pelvis in back/low see Burger and Fuchs, Wien. Klin. Wochenschr., 6, 1927.

216 (10)

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Sm,g., Gynecol. and Obstet., February, 1926, 209-

217a (11) Zeitschr. L uroL Chir., 18, 3/4, 1925. (12) HINMAN AND MORISON: Jour. Urol., 1924, 11/2. (13) TINNER: Wiener uro!. Ges., 10, vi, 1925. Sitzungsber. d. Zeitschr. L urol. Chir., 18, 5/6. 1925. (14) S'.I'AHR: Arch. f. Anat. u. Physiol., l.900. (15) KuMITA: Arch. f. Anat. u. Physiol., 1909. (16) DISSES: Bardelebens Handbuch der Anatomie. (17) Srm,: Mlinch. med. Wochenschr., S. 15, 1926. (18) NECKER: Wiener uroL Ges., 24, ii, 1926. Sitzungsber.: d. Zeitschr. f. urol. ChiL, 20, 5/6. 1926. Compare the figures in this.