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Observations on Injections of the Renal Pelvis: With Special Reference to the Question of Pyelovenous Back-Flow
OBSERVATIONS ON INJECTIONS OF THE RENAL PELVIS WITH SPECIAL REFERENCE TO THE QUESTION OF PYELOVENOUS BACK-FLOW HAROLD H. GILE From the Urological Department, Peter Bent Brigham Hospital, Boston, and the Presbyterian Hospital, New York City
Received for publication June 23, 1927
It has long been known that under certain conditions various substances may enter the general circulation from the renal pelvis. These substances include poisons, true solutions, and colloidal suspensions. The exact route by which they enter the blood stream has been the subject of much experimentation and discussion, and is today an unsettled question. There has been a great lack of uniformity in the results obtained in many investigations of this problem, from the year 1856, when Gignon published some work on the injection of living and dead kidneys, up to the present day. A few report having obtained complete tubular and glomerular injections by way of the ureters, while others, who constitute a majority, have been unable to do so. The probable existence of a back-flow of the contents of the renal pelvis into the veins about the minor calyces, under conditions of a moderate increase of intra-pelvic pressure, was first suggested by Hinman and Lee-Brown in 1924. They termed the phenomenon, "pyelovenous back-flow," and since that time they have contributed further articles on the subject. Their attention was first called to the question when in making routine corrosion specimens of the renal pelvis in cadavers, they frequently noted what were, apparently, venous out-branchings connected with the cast of the pelvis. Using dye injections they were able to obtain venous filling without any tubular injection, 621 THE JOURNAL OF U ROLOGY, VOL. XVIII, NO,
6
622
HAROLD H. GILE
and by radiographic observation of sodium iodide injections, what was assumed to be a filling of the venous system was noted. Dye injected into the pelvis was seen to flow out soon from the renal vein, a phenomenon first noted by Poirier in 1891. All of these results were obtained by pressure lower than the secretory pressure of the kidney being injected, so that the factor of extravasation was felt to be ruled out. From these findings they felt that under certain conditions of intrapelvic pressure there was a direct communication between
FIG.
1.
PHOTOGR~P H OF CORROSION SPECIMEN OF URETER AND TUBULES OF FROG'S KIDNEY
Pressure used- 20 mm. of water
the pelvis and the veins, and that the probable point of communication was in the region of the minor calyces. Bird and Moise failed to confirm these findings, and rer;ort having successfully injected the tubules and glomeruli in living and dead kidneys. I wish to record here some findings of a further attempt to investigate this problem. 1. In many corrosion specimenl3 of the renal pelvis in living and cadaver kidneys of various animals, including the dog, the
OBSERVATIOXS ON IXJECTIONS OF REXAL PELVIS
Fm. 2.
PHOTOMIClWGRAPH AFTER IN,JECTION OF BERLIN BLUE KrnKEY,
Snown-:G DYE
IN THE
r,, LrnxG FR.oG's
TuBULJ"s
Pressure used-20 mm. of water
Fru. 3. CmmosIOC'i
SPECIMEX OF KrnNJcY PELVIS OF
Cow
High pressure--200 mm. Hg; extravasation is shown in lower right hand corner
624
HAROLD H. GILE
sheep, and the cow, no venous out-branchings, as described by Hinman, were obtained. In several instances partial tubular injections were found in the kidney of the cow. 2. The results obtained from injections of dyes in cadaver specimens, under varying controlled pressures, were similar to those of Hinman, in that no satisfactory tubular injection was
Fm. 4. A,
CORROSION SPECIMEN OF KIDNEY PELVIS OF Cow SHOWING PARTIAL
INJECTION OF THE COLLECTING TUBULES;
B,
CLOSE VIEW OF SAME
Pressure used-150 mm. Hg
obtained, dye was seen to run out of the renal vein and the venous system was completely stai.ned. 3. Inspection of opaque solutions injected into cadaver specimens under fluoroscopic and x-ray observation, reproduced Hinman's pictures showing what appeared to be venous filling. (This, however, cannot be considered as definite evidence.) Richard's technique for microscopic observations of the living kidney of the frog offered an opportunity to watch a dye injec-
OBSERV.ATIONS ON IXJECTIOXS OF RENAL PELVIS
normal circulation of the kidney unimpaired. Using tion tying a, small glass cannula in the ureter of a frog method kidney, Berlin Blue was injected at a pressure of 20 mm. vvas seen definitely to go up the tubules ,vater. The
l<'rn. 5 .
PnoTOMICHOGRAPH OF RABBIT'S KIDNEY FOI,LOWING URETERAL IN.JECTION OF LIYING SPEC11'IEN WITH INDIA INK BY HYPODERMIC SYRINGID
Dye is shown in the lumen of small blood vessels. bules. There was no evidence of extrnvasation.
None was found in the tu-
between the lanes of blood vessels in which active circulation was seen to be taking place. Microscopic section of kidneys showed dye in the tubules. Casts of the tubules coming off almost at right angles from the upper end of the ureter were pro--
626
HAROLD H. GILE
FIG. 6. FIG.
6. Low
FIG.
7
POWER PHOTOMICROGRAPH OF RABBIT'S KID;'/EY FOLLOWING URETERAL INJECTION OF INDIGO CARMINE
Dye is shown in interstitial tissue and in blood vessels. the tubules. Pressure used-'.?O mm. Hg. FIG.
7.
None was found in
PHOTOMICROGRAPH OF SECTION THROUGH ONE OF THE CALICES OF RABBIT'S KIDNEY ]'OLLOWING INJECTION OF INDIGO CARMINE
Dye was found in peri-pelvic and interstitial tissue
FIG.
8.
HIGH POWER
PHOTOMICROGRAPH OF PELVIC EPITHELIUM OF RABBIT'S
KIDNEY SHOWING DYE IN AND BETWEEN THE INDIVIDUAL CELLS, AS THOUGH ABSORPTION HAD TAKEN PLACE
OBSERVATIOKS OX INJECTIOXS OF RENAL PELVIS
627
duced in corrosion specimens as shown in the accompanying photograph . 'IVhile this seems to be conclusive demonstration that tubular back-How takes place in the living kidney of the frog, and while it might be assumed that the more complex mammalian struc-
}':w. 9.
PYELOGll.A~i SHOWI~G DIFFUSJGK OF OPAQUE SOLUTION AT UPPER Pou; OF
Rrnm' KID>iEY In this ca.se nephrostomy ha.d been performed one month previously, a.nd this m.ay represent the site of the incision. On the othcr_hand, it ma.y ]Jc venous injection.
tures probably do not differ 1adically in their anatomical and physiological functions from similar structures in the lower forms, rt is, at best, only suggestive evidence of what occurs in the kidney of the warm--blooded animal:cL
0, t,:) Cl)
B Fm. 10. A,
C
PYELOGRAM IN A CASE OF HYDRONEPHROSIS, SHOWING DIFFUSION OF THE OPAQUE SOLUTION FROM THE CALICEs;
PHOTOGRAPH OF SAME KIDNEY SHOWING THE EXTENT OF THE HYDRONEPHROSISj
C,
B,
PYELOGRAM OF SAME KIDNEY EXCISED
Despite the use of varying pressures, a picture similar to that in the living specimen could not be produced in the excised kidney.
OBSERVATIONS OJ\1 IN,TEC'TIOKS OF REN.AL PELVIS
The next step was an attempt to see the same thing mammalian kidney the method :Yiarshall, who through the microscope the circulation of mice's and
Fm. 11.
Pn!LOGRA]\l IN SUPPOSEDLY :;'-;" OI\MAL KIDKEY SHOWING DIFFUSION OF OP,,QUE SOLUTION
This was felt to be due to extravasation from excess pressure, as a repetition of the pyelogram by the gravity method showed only a normal pelvis.
neys. kidneys of the mouse, the rat, and the guinea pig were· placed under the dissecting microscope, ureters were cannulized dyes were injected. The pelvis in these animals
630
HAROLD H. GILE
was covered with so much renal tissue that it was found impossible to make out the pelvic margins distinctly. However, sections taken on these living injected kidneys showed interesting histological pictures which may aid in the final solution of this problem. Excessive pressure gave a subcapsular extravasation. With low pressures between 10 and 20 mm. Hg sustained for five minutes dye was shown between the individual cells lining the pelvis and extending beyond into the interstitial cells about the blood vessels. Dye was seen in the walls of the vessels but very little was found in their lumens, due, undoubtedly, to its having been rapidly carried away by the circulation. Certain areas of the pelvic epithelium seemed to stain more heavily than others and they were apparently at points where the blood vessels directly beneath the pelvis were larger. There was no dye in the lumen of the tubules. If they had been filled the absorption into the surrounding tissues and blood vessels must have been exceedingly rapid. Injection of a living rabbit's kidney pelvis with India ink produced a fairly uniform injection of the blood vessels without showing a trace of it in the tubules. In this case there was no controlled pressure of the injection, it being done by means of a 10-cc. Luer syringe. There was no evidence of extravasation, however. It is interesting to note that 5 cc. of the dye was slowly injected over a period of ten minutes despite the fact that the pelvis and cannula were filled before beginning the injection. PYELOGRAPHIC EVIDENCE
If pyelovenous back-flow occurs as readily as it is contended by Hinman it seemed, from the many pyelograms that were done, mostly without controlled pressure, x-ray pictures similar to those produced by the injection of cadaver kidneys with opaque solutions should be seen frequently. In an examination of several hundred pyelograms, only three were found which suggested either venous or tubular injection. Case 1, in which there was a moderate degree of hydronephrosis, suggests the architecture of the tubules rather than that of the ,·ems.
OBSERVATIONS ON INJECTIONS OF RENAL PELVIS
631
Case 2, where there was a greater degree of hydronephrosis to a ureteral stricture caused by a growth of tun10r tissue surrounding ureter, also giyes the impression of tubular than glomerular filling. This patient died of cancer pyelogram was made. was hours after and the kidney was removed and an was made immediately, under varying pressures, to reproduce T.~BLE 1
Urelerol ·injection e,1;perimcnts NH!-
BER
I
'TYPE OF KID"'.\!E Y
PRESSl7HE USED
'l'I0::-1 I DUHA-1
HESl.~J_TS
.-\. Corrosion specimens by acetone-celloidin injection of excised kidneys nu:rw,tes
6
10 6 1 1 1
Dog Sheep Sheep Veal Cow Cow
50 mm. Hg. 50 mm. Hg. 10 mm. Hg 70 mm. Hg 120 mm. Hg 150 mm. Hg
5
5 5 5 10 10
:'\:' o venous out-branching occurred, partial tubular injection only in the kidney of the cow. B. Same on living kidneys
1
Guinea pig
10 mm. Hg
1 1
Guinea pig Frog
5 mm. Hg 20 mm. water
Immediate suhcapsular extravasation Pelvis injection only Tubular filling
C. Injection of dye (Berlin Blue) in excised kidneys
2 2
1
Human kidney (re-moved at autopsy 8 hours af-ter death; 111j ectecl 30 minutes later) Sheep Cow Dog
,50 mm. Hg
5
No tubular injection. J\fter 3 minutes dye ran out of renal vein
50 mm. Hg JOO mm. Hg 50 mm. Hg
5
No tubular injection No tubular injection No tubular injection
5
5
632
HAROLD H. GILE TABLE
ND~I-
BEH
TYPE OF KIDNEY
!-Concluded
PRESSURE USED
I
DURATIO:N'"
I
RESULTS
D. Injection of dye (Indigo carmine) in living kidneys minute8
5
Frog
1 2
Guinea pig Rabbits
1 1
Guinea pig Dog (Berlin Blue used)
5-10 mm. water
2
10 mm. Hg 20 mm. Hg
2
5 mm. Hg 100 mm. Hg
2 5
Tubular filling seen un• der direct microscopic vision Extravasation No tubular filling, dye seen 1n and between cells of pelvic epithelium; shown in microphotograph No tubular filling No tubular injection
Two living rabbit's kidneys injected with India ink, showed the ink particles in the small blood vessels, no tubular injection. It was difficult to be sure about the Blue dyes as they did not show as clearly as did the India ink. E. Injection of opaque solutions (sodium iodide 20 per cent). 2
Cows
75 mm. Hg
3
2
Sheep
50 mm. Hg
3
Excised kidneys
Under x-ray showed ap parent venous injec tion As above
Injection method used was that described and used hy Hinman (2).
the pyelogram in the excised specimen. As shown in the photographs, this could not be accomplished, no suggestion of tubular or venous filling or extravasation being demonstrated. In case 3 a pyelogram was done as an aid to the diagnosis of a mass in the right upper quadrant. The mass proved at operation to be a hemangioma of the liver, and the kidney was felt to be a normal one. The pyelogram was repeated before operation on account of the out-branchings of the opaque solution from the pelvis. On the second occasion the gravity method of injection was used, and the out-branchings were not reproduced. These pyelograms, especially figure 11 in case 1, resembled
OBSERVATIOJ\S ON INJECTIOKS OF RENAL PELVIS
633
considerably a pyelogram presented by Hinman in a recent article, where the diffusion of the opaque solution is taken by him to represent pyelovenous back-flow. In case 1 a nephrotomy wound had been made in the kidney, one month before the pyel-ogram was done, and the diffusion here may indicate the site of that incision. Though these pictures may appear to represent the fillings of the venous system, it seems that emphasis must be made on the fact that there is no conclusive proof of iL DISCUSSION
That, under certain conditions of increased pressure, substances may enter the blood stream from the renal pelvis, there is no doubt. That this occurs through a direct communicfttion between the pelvis and the yenous system as suggested by Hinman and Lee-Brown, there is great doubt. In a recent paper by Hinman and Redewell the factors of diapedesis, osmo:-;is, and permeability of membranes are considered of probable irn.portance.. Lee-Brown, in a paper of this year, states as before, that a direct communication in the fornices of the minor calyces is opened when the pelvis is distended. He further says that the venous system may be filled by direct injection of the renal parenchyma, or through a minute tear in the pelyic epithelium. He admits that the collecting tubules can be injected, but does not consider them a factor in the production of back-flow. While the experiments of Hinman, most of which have here been repeated with the same findings, prove that there is a flow from the pelvis to the veins, the exact mechanism by which it occurs, whether the route is a direct or indirect one, and the many factors involved, cannot be considered as solved. There are many factors which must have a bea,ring in the condition, some are, in a degree, determinative ones, such as the thickness of the solution, the pressure used, the freshness of the specimen, the size and type of specimen, and whether it is living or dead. Other factors are indeterminate, such as osmosis, diapedesis, and permeability of membranes, ,vhich are discussed by Hinman. The question of the lymphatics of the kidney, the existence of which ,vere demonstrated by Teichman, Sappey, and Stahr,
634
HAROLD H. GILE
though seemingly of no great importance, must not be passed by without consideration. With these, and other possible factors of importance, it seems necessary, first of all to have living kidneys from which any conclusions are to be drawn. Deductions made from work on cadaver specimens, do not necessarily apply to living ones. SUMMARY
In corrosion specimens of the renal pelvis of cadaver specimens, no venous out-branchings were obtained, except where apparent extravasation had occurred. The results from dye injections were similar to those of Hinman: the venous system was injected regularly, the tubules were never more than partially injected and that occurred rarely. Observations of opaque solutions injected under the x-ray confirmed those made by Hinman. None of these findings, however, demonstrate how the substances get from the pelvis to the blood stream. Normally there is no intrapelvic pressure. With the occurrence of a positive pressure there may be microscopic ruptures, filtration, osmosis, increased permeability of the pelvic membrane, lymphatic absorption, or the opening up of a direct communication already present in the angles of the minor calyces as conceived by Hinman and Lee-Brown. There is no doubt that the tubules may be partially injected, but from the finding of dye in the blood vessels and not in the tubules, following injection of living mammalian kidneys, it would seem that they do not play a large part in the production of back-flow. The living kidney of the frog apparently presents a different mechanism as there the tubules were easily filled. CONCLUSION
The term "pyelovenous back-flow," if understood in the general sense to mean that substances may go from the renal pelvis to the venous circulation, is a good one.
OBSERVATIONS ON IN.JECTIOXS OF RENAL PELVIS
635
It is probable that this phenomenon does not occur by way of the tubules. The exact route by which it does occur not yet been demonstrated. REFERENCES (1) HINMY"i AND LEE··BROWN: Pyelovenous backf!ow; its relation to pelvic a.bsorption, to hydronephrosis, and to accidents of pyelography. J our. Amer. Med. Assoc., 1924, lxxxii, 607,-613. (2) HINMAN, MORISON, AND LEE-BROWN: Methods of demonstrating the circulation in general, as applied to a study of the renal circulation in particular. Jour Amer. Med. Assoc., 1923, lxxxi, 177-184. (3) HINMAN, FRANK, AND REDEWILL, F. H.: Pyelovenous backf!ow. Trans. Sect. Path. and Physiol., Amer. Med. Assoc., 1926, July. (4) BrnD AND MorsE: Pyelovenous backflow. Jour. Amer. Med. Assoc., 1926, lxxxvi, 661-663. (5) Pornnm, M.: Compt. rend. Soc. de biol., 1891, p. 585. (6) E:En~s AND ::VIonAN: The damage done by pyelography, Amer. Jour. Med. Sci., 1915, cxlix, 30-4L (7) l\L.\SON, J. JVL: Dangers attending injections of the kidney pelvis for pyelog-· raphy. Jour. Amer. Med. Assoc., !xii, 839 (March 14), 1914. (8) EDWARDS, J. G., AND MARSHALL, E. K., .Ju.: Microscopic observations of the living kidney after the injection of phenolsulphonephthalein. Amer. J our. Physiol., 1924, !xx, 489. (9) RICHARDS, A. N,. Kidney function. Harvey Lectures, 1920-1921, p. 163. (10) IC: The phenomenon of pyelovenous backflow. J our. U rol. l<'ebruary, 1927, xvii, 105. (ll.) HINMAN, F.: Pyelovenous backflow at the time of pyelography, Surg., Gynecol., and Obstet., May, 1927, 592.
Received for publication June 23, 1927
It has long been known that under certain conditions various substances may enter the general circulation from the renal pelvis. These substances include poisons, true solutions, and colloidal suspensions. The exact route by which they enter the blood stream has been the subject of much experimentation and discussion, and is today an unsettled question. There has been a great lack of uniformity in the results obtained in many investigations of this problem, from the year 1856, when Gignon published some work on the injection of living and dead kidneys, up to the present day. A few report having obtained complete tubular and glomerular injections by way of the ureters, while others, who constitute a majority, have been unable to do so. The probable existence of a back-flow of the contents of the renal pelvis into the veins about the minor calyces, under conditions of a moderate increase of intra-pelvic pressure, was first suggested by Hinman and Lee-Brown in 1924. They termed the phenomenon, "pyelovenous back-flow," and since that time they have contributed further articles on the subject. Their attention was first called to the question when in making routine corrosion specimens of the renal pelvis in cadavers, they frequently noted what were, apparently, venous out-branchings connected with the cast of the pelvis. Using dye injections they were able to obtain venous filling without any tubular injection, 621 THE JOURNAL OF U ROLOGY, VOL. XVIII, NO,
6
622
HAROLD H. GILE
and by radiographic observation of sodium iodide injections, what was assumed to be a filling of the venous system was noted. Dye injected into the pelvis was seen to flow out soon from the renal vein, a phenomenon first noted by Poirier in 1891. All of these results were obtained by pressure lower than the secretory pressure of the kidney being injected, so that the factor of extravasation was felt to be ruled out. From these findings they felt that under certain conditions of intrapelvic pressure there was a direct communication between
FIG.
1.
PHOTOGR~P H OF CORROSION SPECIMEN OF URETER AND TUBULES OF FROG'S KIDNEY
Pressure used- 20 mm. of water
the pelvis and the veins, and that the probable point of communication was in the region of the minor calyces. Bird and Moise failed to confirm these findings, and rer;ort having successfully injected the tubules and glomeruli in living and dead kidneys. I wish to record here some findings of a further attempt to investigate this problem. 1. In many corrosion specimenl3 of the renal pelvis in living and cadaver kidneys of various animals, including the dog, the
OBSERVATIOXS ON IXJECTIONS OF REXAL PELVIS
Fm. 2.
PHOTOMIClWGRAPH AFTER IN,JECTION OF BERLIN BLUE KrnKEY,
Snown-:G DYE
IN THE
r,, LrnxG FR.oG's
TuBULJ"s
Pressure used-20 mm. of water
Fru. 3. CmmosIOC'i
SPECIMEX OF KrnNJcY PELVIS OF
Cow
High pressure--200 mm. Hg; extravasation is shown in lower right hand corner
624
HAROLD H. GILE
sheep, and the cow, no venous out-branchings, as described by Hinman, were obtained. In several instances partial tubular injections were found in the kidney of the cow. 2. The results obtained from injections of dyes in cadaver specimens, under varying controlled pressures, were similar to those of Hinman, in that no satisfactory tubular injection was
Fm. 4. A,
CORROSION SPECIMEN OF KIDNEY PELVIS OF Cow SHOWING PARTIAL
INJECTION OF THE COLLECTING TUBULES;
B,
CLOSE VIEW OF SAME
Pressure used-150 mm. Hg
obtained, dye was seen to run out of the renal vein and the venous system was completely stai.ned. 3. Inspection of opaque solutions injected into cadaver specimens under fluoroscopic and x-ray observation, reproduced Hinman's pictures showing what appeared to be venous filling. (This, however, cannot be considered as definite evidence.) Richard's technique for microscopic observations of the living kidney of the frog offered an opportunity to watch a dye injec-
OBSERV.ATIONS ON IXJECTIOXS OF RENAL PELVIS
normal circulation of the kidney unimpaired. Using tion tying a, small glass cannula in the ureter of a frog method kidney, Berlin Blue was injected at a pressure of 20 mm. vvas seen definitely to go up the tubules ,vater. The
l<'rn. 5 .
PnoTOMICHOGRAPH OF RABBIT'S KIDNEY FOI,LOWING URETERAL IN.JECTION OF LIYING SPEC11'IEN WITH INDIA INK BY HYPODERMIC SYRINGID
Dye is shown in the lumen of small blood vessels. bules. There was no evidence of extrnvasation.
None was found in the tu-
between the lanes of blood vessels in which active circulation was seen to be taking place. Microscopic section of kidneys showed dye in the tubules. Casts of the tubules coming off almost at right angles from the upper end of the ureter were pro--
626
HAROLD H. GILE
FIG. 6. FIG.
6. Low
FIG.
7
POWER PHOTOMICROGRAPH OF RABBIT'S KID;'/EY FOLLOWING URETERAL INJECTION OF INDIGO CARMINE
Dye is shown in interstitial tissue and in blood vessels. the tubules. Pressure used-'.?O mm. Hg. FIG.
7.
None was found in
PHOTOMICROGRAPH OF SECTION THROUGH ONE OF THE CALICES OF RABBIT'S KIDNEY ]'OLLOWING INJECTION OF INDIGO CARMINE
Dye was found in peri-pelvic and interstitial tissue
FIG.
8.
HIGH POWER
PHOTOMICROGRAPH OF PELVIC EPITHELIUM OF RABBIT'S
KIDNEY SHOWING DYE IN AND BETWEEN THE INDIVIDUAL CELLS, AS THOUGH ABSORPTION HAD TAKEN PLACE
OBSERVATIOKS OX INJECTIOXS OF RENAL PELVIS
627
duced in corrosion specimens as shown in the accompanying photograph . 'IVhile this seems to be conclusive demonstration that tubular back-How takes place in the living kidney of the frog, and while it might be assumed that the more complex mammalian struc-
}':w. 9.
PYELOGll.A~i SHOWI~G DIFFUSJGK OF OPAQUE SOLUTION AT UPPER Pou; OF
Rrnm' KID>iEY In this ca.se nephrostomy ha.d been performed one month previously, a.nd this m.ay represent the site of the incision. On the othcr_hand, it ma.y ]Jc venous injection.
tures probably do not differ 1adically in their anatomical and physiological functions from similar structures in the lower forms, rt is, at best, only suggestive evidence of what occurs in the kidney of the warm--blooded animal:cL
0, t,:) Cl)
B Fm. 10. A,
C
PYELOGRAM IN A CASE OF HYDRONEPHROSIS, SHOWING DIFFUSION OF THE OPAQUE SOLUTION FROM THE CALICEs;
PHOTOGRAPH OF SAME KIDNEY SHOWING THE EXTENT OF THE HYDRONEPHROSISj
C,
B,
PYELOGRAM OF SAME KIDNEY EXCISED
Despite the use of varying pressures, a picture similar to that in the living specimen could not be produced in the excised kidney.
OBSERVATIONS OJ\1 IN,TEC'TIOKS OF REN.AL PELVIS
The next step was an attempt to see the same thing mammalian kidney the method :Yiarshall, who through the microscope the circulation of mice's and
Fm. 11.
Pn!LOGRA]\l IN SUPPOSEDLY :;'-;" OI\MAL KIDKEY SHOWING DIFFUSION OF OP,,QUE SOLUTION
This was felt to be due to extravasation from excess pressure, as a repetition of the pyelogram by the gravity method showed only a normal pelvis.
neys. kidneys of the mouse, the rat, and the guinea pig were· placed under the dissecting microscope, ureters were cannulized dyes were injected. The pelvis in these animals
630
HAROLD H. GILE
was covered with so much renal tissue that it was found impossible to make out the pelvic margins distinctly. However, sections taken on these living injected kidneys showed interesting histological pictures which may aid in the final solution of this problem. Excessive pressure gave a subcapsular extravasation. With low pressures between 10 and 20 mm. Hg sustained for five minutes dye was shown between the individual cells lining the pelvis and extending beyond into the interstitial cells about the blood vessels. Dye was seen in the walls of the vessels but very little was found in their lumens, due, undoubtedly, to its having been rapidly carried away by the circulation. Certain areas of the pelvic epithelium seemed to stain more heavily than others and they were apparently at points where the blood vessels directly beneath the pelvis were larger. There was no dye in the lumen of the tubules. If they had been filled the absorption into the surrounding tissues and blood vessels must have been exceedingly rapid. Injection of a living rabbit's kidney pelvis with India ink produced a fairly uniform injection of the blood vessels without showing a trace of it in the tubules. In this case there was no controlled pressure of the injection, it being done by means of a 10-cc. Luer syringe. There was no evidence of extravasation, however. It is interesting to note that 5 cc. of the dye was slowly injected over a period of ten minutes despite the fact that the pelvis and cannula were filled before beginning the injection. PYELOGRAPHIC EVIDENCE
If pyelovenous back-flow occurs as readily as it is contended by Hinman it seemed, from the many pyelograms that were done, mostly without controlled pressure, x-ray pictures similar to those produced by the injection of cadaver kidneys with opaque solutions should be seen frequently. In an examination of several hundred pyelograms, only three were found which suggested either venous or tubular injection. Case 1, in which there was a moderate degree of hydronephrosis, suggests the architecture of the tubules rather than that of the ,·ems.
OBSERVATIONS ON INJECTIONS OF RENAL PELVIS
631
Case 2, where there was a greater degree of hydronephrosis to a ureteral stricture caused by a growth of tun10r tissue surrounding ureter, also giyes the impression of tubular than glomerular filling. This patient died of cancer pyelogram was made. was hours after and the kidney was removed and an was made immediately, under varying pressures, to reproduce T.~BLE 1
Urelerol ·injection e,1;perimcnts NH!-
BER
I
'TYPE OF KID"'.\!E Y
PRESSl7HE USED
'l'I0::-1 I DUHA-1
HESl.~J_TS
.-\. Corrosion specimens by acetone-celloidin injection of excised kidneys nu:rw,tes
6
10 6 1 1 1
Dog Sheep Sheep Veal Cow Cow
50 mm. Hg. 50 mm. Hg. 10 mm. Hg 70 mm. Hg 120 mm. Hg 150 mm. Hg
5
5 5 5 10 10
:'\:' o venous out-branching occurred, partial tubular injection only in the kidney of the cow. B. Same on living kidneys
1
Guinea pig
10 mm. Hg
1 1
Guinea pig Frog
5 mm. Hg 20 mm. water
Immediate suhcapsular extravasation Pelvis injection only Tubular filling
C. Injection of dye (Berlin Blue) in excised kidneys
2 2
1
Human kidney (re-moved at autopsy 8 hours af-ter death; 111j ectecl 30 minutes later) Sheep Cow Dog
,50 mm. Hg
5
No tubular injection. J\fter 3 minutes dye ran out of renal vein
50 mm. Hg JOO mm. Hg 50 mm. Hg
5
No tubular injection No tubular injection No tubular injection
5
5
632
HAROLD H. GILE TABLE
ND~I-
BEH
TYPE OF KIDNEY
!-Concluded
PRESSURE USED
I
DURATIO:N'"
I
RESULTS
D. Injection of dye (Indigo carmine) in living kidneys minute8
5
Frog
1 2
Guinea pig Rabbits
1 1
Guinea pig Dog (Berlin Blue used)
5-10 mm. water
2
10 mm. Hg 20 mm. Hg
2
5 mm. Hg 100 mm. Hg
2 5
Tubular filling seen un• der direct microscopic vision Extravasation No tubular filling, dye seen 1n and between cells of pelvic epithelium; shown in microphotograph No tubular filling No tubular injection
Two living rabbit's kidneys injected with India ink, showed the ink particles in the small blood vessels, no tubular injection. It was difficult to be sure about the Blue dyes as they did not show as clearly as did the India ink. E. Injection of opaque solutions (sodium iodide 20 per cent). 2
Cows
75 mm. Hg
3
2
Sheep
50 mm. Hg
3
Excised kidneys
Under x-ray showed ap parent venous injec tion As above
Injection method used was that described and used hy Hinman (2).
the pyelogram in the excised specimen. As shown in the photographs, this could not be accomplished, no suggestion of tubular or venous filling or extravasation being demonstrated. In case 3 a pyelogram was done as an aid to the diagnosis of a mass in the right upper quadrant. The mass proved at operation to be a hemangioma of the liver, and the kidney was felt to be a normal one. The pyelogram was repeated before operation on account of the out-branchings of the opaque solution from the pelvis. On the second occasion the gravity method of injection was used, and the out-branchings were not reproduced. These pyelograms, especially figure 11 in case 1, resembled
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considerably a pyelogram presented by Hinman in a recent article, where the diffusion of the opaque solution is taken by him to represent pyelovenous back-flow. In case 1 a nephrotomy wound had been made in the kidney, one month before the pyel-ogram was done, and the diffusion here may indicate the site of that incision. Though these pictures may appear to represent the fillings of the venous system, it seems that emphasis must be made on the fact that there is no conclusive proof of iL DISCUSSION
That, under certain conditions of increased pressure, substances may enter the blood stream from the renal pelvis, there is no doubt. That this occurs through a direct communicfttion between the pelvis and the yenous system as suggested by Hinman and Lee-Brown, there is great doubt. In a recent paper by Hinman and Redewell the factors of diapedesis, osmo:-;is, and permeability of membranes are considered of probable irn.portance.. Lee-Brown, in a paper of this year, states as before, that a direct communication in the fornices of the minor calyces is opened when the pelvis is distended. He further says that the venous system may be filled by direct injection of the renal parenchyma, or through a minute tear in the pelyic epithelium. He admits that the collecting tubules can be injected, but does not consider them a factor in the production of back-flow. While the experiments of Hinman, most of which have here been repeated with the same findings, prove that there is a flow from the pelvis to the veins, the exact mechanism by which it occurs, whether the route is a direct or indirect one, and the many factors involved, cannot be considered as solved. There are many factors which must have a bea,ring in the condition, some are, in a degree, determinative ones, such as the thickness of the solution, the pressure used, the freshness of the specimen, the size and type of specimen, and whether it is living or dead. Other factors are indeterminate, such as osmosis, diapedesis, and permeability of membranes, ,vhich are discussed by Hinman. The question of the lymphatics of the kidney, the existence of which ,vere demonstrated by Teichman, Sappey, and Stahr,
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though seemingly of no great importance, must not be passed by without consideration. With these, and other possible factors of importance, it seems necessary, first of all to have living kidneys from which any conclusions are to be drawn. Deductions made from work on cadaver specimens, do not necessarily apply to living ones. SUMMARY
In corrosion specimens of the renal pelvis of cadaver specimens, no venous out-branchings were obtained, except where apparent extravasation had occurred. The results from dye injections were similar to those of Hinman: the venous system was injected regularly, the tubules were never more than partially injected and that occurred rarely. Observations of opaque solutions injected under the x-ray confirmed those made by Hinman. None of these findings, however, demonstrate how the substances get from the pelvis to the blood stream. Normally there is no intrapelvic pressure. With the occurrence of a positive pressure there may be microscopic ruptures, filtration, osmosis, increased permeability of the pelvic membrane, lymphatic absorption, or the opening up of a direct communication already present in the angles of the minor calyces as conceived by Hinman and Lee-Brown. There is no doubt that the tubules may be partially injected, but from the finding of dye in the blood vessels and not in the tubules, following injection of living mammalian kidneys, it would seem that they do not play a large part in the production of back-flow. The living kidney of the frog apparently presents a different mechanism as there the tubules were easily filled. CONCLUSION
The term "pyelovenous back-flow," if understood in the general sense to mean that substances may go from the renal pelvis to the venous circulation, is a good one.
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It is probable that this phenomenon does not occur by way of the tubules. The exact route by which it does occur not yet been demonstrated. REFERENCES (1) HINMY"i AND LEE··BROWN: Pyelovenous backf!ow; its relation to pelvic a.bsorption, to hydronephrosis, and to accidents of pyelography. J our. Amer. Med. Assoc., 1924, lxxxii, 607,-613. (2) HINMAN, MORISON, AND LEE-BROWN: Methods of demonstrating the circulation in general, as applied to a study of the renal circulation in particular. Jour Amer. Med. Assoc., 1923, lxxxi, 177-184. (3) HINMAN, FRANK, AND REDEWILL, F. H.: Pyelovenous backf!ow. Trans. Sect. Path. and Physiol., Amer. Med. Assoc., 1926, July. (4) BrnD AND MorsE: Pyelovenous backflow. Jour. Amer. Med. Assoc., 1926, lxxxvi, 661-663. (5) Pornnm, M.: Compt. rend. Soc. de biol., 1891, p. 585. (6) E:En~s AND ::VIonAN: The damage done by pyelography, Amer. Jour. Med. Sci., 1915, cxlix, 30-4L (7) l\L.\SON, J. JVL: Dangers attending injections of the kidney pelvis for pyelog-· raphy. Jour. Amer. Med. Assoc., !xii, 839 (March 14), 1914. (8) EDWARDS, J. G., AND MARSHALL, E. K., .Ju.: Microscopic observations of the living kidney after the injection of phenolsulphonephthalein. Amer. J our. Physiol., 1924, !xx, 489. (9) RICHARDS, A. N,. Kidney function. Harvey Lectures, 1920-1921, p. 163. (10) IC: The phenomenon of pyelovenous backflow. J our. U rol. l<'ebruary, 1927, xvii, 105. (ll.) HINMAN, F.: Pyelovenous backflow at the time of pyelography, Surg., Gynecol., and Obstet., May, 1927, 592.