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III. The Function of the Uretfro-Vesical Valve and the Experimental Production of Hydroureters Without Obstruction
III. THE FUNCTION OF THE URETFROVALVE AND THE EXPERIMENTAL PRODUCTION OF HYDROURETERS ViTITHOUT OBSTRUCTION CHARLES lVL GRUBER Prom the Department of Pharmacology, Washington University School of M edic1:ne, St. Louis, lv[issouri
The production of hydroureters with partial or complete obstruction of the ureter is a common observation both experimentally (1) and clinically (2) but the experimental production of a hydrometer without obstruction has been observed in a instances only. In these isolated cases the authors believed some spasm of the ureter or other partial obstructive process of injury was their cause (3). Congenital hydrometers of which the uretero-vesical valves are found to be incompetent and the ureteral orifices patent have been described (4) frequently in the clinical literature. In many instances, however, these ureters were first discovered in the patient after middle age and because no obstruction was noted at the time of observation and no history of such a tion in these patients could be obtained, the ureters were regarded as congenital. Caulk (5) was the first to describe a congenital "megaloureter'' patent uretero-vesical orifices. Since his description many ureters which had previously been classed as hydroureters are now reclassed as megalo-ureters (6). Young (7) observed a single instance of a hydroureter in which the ureterovesical valve was incompetent, and in which no obstruction was noted. He believed that the dilated ureter was the result of some obstruction, either a spasm or a stone, which had disappeared but had left the ureter permanently darn.aged. Sampson (8) after injuring the mucosa of the ureteral orifices noted no increase in the regurgitation of fluids from the bladder 161 THE JOURNAL OF' UROLOGY 1 YOL. XXIII 1 KO.
2
162
CHARLES M. GRUBER
into the ureters. His findings were confirmed by Graves and Davidoff (9). On the other hand Courtade and Guyon (10) noted an increase in the number of regurgitations in dogs when they cut the "straps" to the uretero-vesical orifices. In a series of ten dogs, 3 females and 7 males, Draper and Braasch (11) studied the function of the uretero-vesical valve and the advisability of performing meatotomy in human beings. In these dogs one uretero-vesical valve was cut; the other was left intact. Thirty-four to one hundred and sixty-three days later the animals were killed and the ureters investigated. A hydrometer on the operated side was found in one instance only, in the dog killed one hundred and sixty-three days following the operation. Since they observed no changes in nine other animals, similarly treated, they believed the hydrometer in this single case to be caused by something other than the patent orifice. Their article does not say whether or not examinations were made of the condition of the uretero-vesical valves nor of their competency at autopsy. They tentatively concluded that in experienced hands there is little or no danger to human beings of immediate hemorrhage, sepsis or later injury to the kidney, from the operation of meatotomy through the operative cystoscope. The experiments were repeated with some modifications by Stewart and Barber (12). In addition to cutting the ureterovesical valve they stripped the ureter of all nerve, vessel and fascial connections. In these animals they observed urinary stasis and kidney distention in 66 per cent of the cases. Andler (13) believed it possible to produce hydrometers in animals by denervating the kidney and ureter without the necessity of cutting the uretero-vesical valve. Recently Gruber (14) studied the function of the ureterovesical valve and noted excision of the valve to cause the ureter to assume at all times the same pressure as that within the bladder. Since no proof of the cause of these various sporadic cases of hydrometer with patent orifice and without apparent obstruction has been given, the possibility that the increased pressure within the ureter was the cause of the hydrometer seemed a plausible theory.
FUNCTION OF URETERO-YESICAL YALYE
163
METHOD
Sixteen dogs and 2 cats were operated on under complete ether anesthesia with aseptic precautions. The bladder was ap-
Fm. 1.
DRAWING OF SECTION OF A PIG'S BLADDER SHOWING LEFT HYDROURETER AND LARGE INFLAMED EDEMATOUS lNTRA-VE8ICAL URETER OR URETEROVESICAL VALVE
Left ureter measured 15 mm. in diameter; right 3 mm. Left uretero-vesical valve twice the width and thickness of the right. All parts drawn to scale, magnification X 2. R.U., right ureter; L.U., left ureter; B., dorsal surface of bladder wall toward the dome; I.JYI.U., intra-mural ureter; I. V.U., intra-vesical ureter or ureterovesical valve; U.O., ureteral orifice; T., Bell's muscle and trigone; U., urethra.
164
CHARLES M. GRUBER
proached by a mid-lower abdominal incision in females and lateral incision in males. The bladder was brought out as gently
FIG.
2. PHOTOMICROGRAPH OF A LONGITUDINAL SECTION TAKEN THROUGH THE LEFT URETER, BLADDER AND URETERO-VESICAL VALVE OF BLADDER ILLUSTRATED IN FIGURE 1
B., bladder wall; U., ureter; I.M.U., intra-mural ureter; I.V.U., intra-vesical ureter or uretero-vesical valve., U.O., ureteral orifice. Note the thickness of valve here pictured and that of the normal pig valve illustrated by Gruber (15), figure_3. Magnification X 5.6.
Fm.
3. RECORD SHOWING CHANGES IN PRESSURE IN JVIILLIMETERS OF MERCURY w·ITHIN THE URETERS WITH CHANGES IN PRESSURE WITHIN THE BLADDER PICTURED IN FIGURE 1
1, changes in pressure within the apparently normal right ureter; 2, Horizontal line; 3, changes in intra-vesical pressure: i, increases; -l , decreases; 4, changes in pressure within the hydro-ureter with megelo-uretero-vesical valve. A and B the same except for interchanging the manometer attached to the ureters. Valve 1 competent for low pressures only; valve 4 incompetent to all changes in intra-vesical pressures. Reduced½-
as possible avoiding trauma and opened by a median ventral incision, parallel with the long axis. The operative wound was
FUNC'l'ION OF URETERO-VESICAL VALVE
165
about 2 cm. in length having its point of origin well toward the neck the bladder. The viscus was then evaginated on the operator's index finger which was applied to the dorsal surface. By this procedure the ureteric slits were usually brought plain view. A small probe was passed into one of the
FIG. 4. DRAWING OF POR'.1'ION OF BLADDER OF DOG 5, TABLE l uretern-vesical valve was excised 169 days before the animal was killed. All parts drawn to scale, magnification X 2. Left ureter measured 5 mm. in diameter; that of the right 2.5 mm. Left valve completely missing and ureter orifice patent. No obstruction or partial obstruction noted. R.U., right ureter; L.U., left ureter; B., bladder wall ventral aspect of dorsal surface; I.lvl.U., intra-mural ureter; I.V.U., intra-vesical ureter; U.O., ureteral orifice; X, scar of excised valve; 'T., trigone with Bell's muscle; U., urethra; P., verumontanum. 1Left
vesical ureters, usually the left, and with a small pair of slender bladed scissors the ventral half of the valve was excised. The bladder wall was tightly closed with three layers of sutures the abdominal wound was also closed without drainage. this ~n,wrl'" not a single instance of fistula occurred.
TABLE 1
Showing the effect of cutting the uretero-vesical valve in dogs 'upon the cross-secl'ion of 'it.s "Ureter ns coin pared to that of the other with the 'intact valve
""0
DATE
"' "'.,, "":a
"'~z )l
OF
".,, z -"'-
-1
~
OPERA-
TION
URETEROVESICAL
VALVE CUT
ANIMAL KILLED
APPEARANCE OF URETERAL ORIFICE AT AUTOPSY
Left
w
Right
---
9
6/21/27 Left
2
9
6/23/27* Left
3
9
6/27/27
Left
4
9
6/27/27
Left
12/19/27
5
ci'
6/28/27
Left
6
9
7/ 7/27
Left
2/ 4/28 Valve missing; no Normal obstruction. Orifice patent 12/19/27
CHANGES IN INTRA-URETERAL PRESSURE WITH CHANGES IN INTRA-VERICAL PRESSURE
Left
Right
Reflux with all increuserl pressnres
Valve competent. No change
Valve n1issing; complete obstruction
Normal
0
1/10/28t One-fourth of valve; re1naining valve competent. Noob· struction
Nonnal
Valve missing. Orifice patent. No obstruction
12/14/27
Valve missing. Orifice patent. No obstruction
12/19/27
One-third of valve Normal remaining; valve competent. No obstruction
COKDI'l'IOI\~ 01•' UHE1'EH AT AU1'0PSY
Left
Right Left ---Dilated hy- Normal Pelvis clilate(l clroureter
Right ____ >J'ormal
Valve c01n- Enormously Normal petent. dilated hyNo change droureter
Twice the nor- Normal mal size. Complete atrophy and absorption of kidney tissue
Valve competent to withstand 60 n1m. Hg pressure
Valve corn_- Nonnal petent. ~o chang:e
Nornial
Norrnal
Normnl
Normal
Reflux with all increases in pressure
Valve com- Dilated hypetent. droureter No change
Normal
Nonnal
Normal
Normal
Reflux with all increases in pressure
Valve con1- Dilated hypetent. droureter No change
Norrnal
Pel vis dilated
Norma!
Nonnal
Nonnal
Normal
>--"
°'°'
CONDITIO~ OF' KIDNJ
Valve competent Valve com- Norrnal to withstand all petent. increases in No change pressures tested
,
7
c:J' 12/28/27
Left
2/13/28
One-fifth of valve Normal remaining. No obstruction. Regurgitation upon compressing bladder contents
Valve competent Valve com- Dilated hyto pressures bepetent. droureter low 14 mm. Hg. No change Reflux with all pressures above
Normal
Normal
Normal
8
c:J' 12/28/27
Left
2/11/28
Valve missing. Ureter patent. No obstruction
Normal
Reflux with all increases in pressure
Normal
Pelvis dilated
Normal
9
c:J' 12/29/27
Right
2/13/28
Normal
Valve miss- Valve competent. Reflux with ing. UreNo change inall ter patent. creased No obpressures struction
Normal
Dilated hydro-
Normal
Normal
Megaloureter
Valve com- Dilated hypetent. droureter No change
ureter
10
c:J'
2/27/28
Left
5/ 3/28
Valve missing. Complete obstructio~ of ureter
Normal
11
c:J'
2/27/28
Right
5/ 3/28
Normal
Valve missing. No obstruction
Valve competent. Reflux with Normal No change all increased h1travesical pressures
Slightly Normal dilated
Normal
12
c:J'
3/ 3/28
Right
3/20/28t Normal
Valve missing. No obstruction
Valve competent. Reflux with Normal No change inall creased intravesical
Slightly
Normal
Norn1al
Normal
Normal
>-'
~
0
Valves competent. No changes
Normal
Fibrosed small Slight kidney hypertrophy
larger
than left (?)
pressures
13
c:J'
3/ 3/28
Left
5/ 4/28
Valve missing. Normal No obstruction
' Animal aborted on the eighth day after operation. t Animal died of pneumonia.
Reflux with all increases in pressure
Valve com- Slightly dipetent. lated No change!
Normal
TABLE ]--Continued
'"0 DATE
C,
""" '"~
01<'
~ ~
8~
OPERA-
el
'HON
~ z -- -14 ci' 3/ 5/28
URE'l'EllOVESICA.L VALVE CUT
Right
ANB-IAL KILLED
APPEARANCE OF URETERAL ORIFICE AT AUTOPSY
Left --5/ 3/28 Nonnal
15
ci'
3/ 5/28
Left. Opera- 3/22/2St Bladder wound healed. Compertion plete obstrucformed by tion an assistant, J. H. R Ureter incorporated in bladder walJ wound in sewing up bladder
16
ci'
3/ 5/28
Left
~
5/ 4/28
Valve missing. very Orifice small. Partial obstruction
Right Valve missing. No obstruction
CHANGES IN INTRA-URETERAL PRESSURE WITH CHANGES IN INTRA-VESICAL PRESSURE
Left
Right
Valve competent. Reflux with inNo change all creases in pressure
Norn1al
0
Normal
Reflux with high pressures
COND!'l'"ION OF' UR.lGTEH AT AUTOPSY
Left Normal
Left Right ---Slightly Norrnal dilated
Valve com- Enormously Norrnal dilated hypetent. No change droureter
Valve com- Marked dipetent. latation No change
CONDITION OF KIDSEY
Normal
Right --Normal
One and onethird times normal size. Some atrophy of kidney substance hydronephrosis
Slight hype troph y
Normal
Normal
FUNCTION OF URETERO-VESICAL VALVE
169
a period of time varying in the different cases from forty-five to two hundred and twenty-eight days after the operation the animals were anesthetized with ether; the abdomen opened and the bladder, ureters and kidneys studied while the animals were still living. The animals were then killed and the method of investigation from then on was the same as that described in previous communications (14 and 15). In addition to the animals operated on we were fortunate in obtaining two pig bladders with hydroureters attached. In both cases no obstruction was found. Both uretero-vesical valves appeared intact (see fig. 1), but there was considerable inflammation and edema of the ureteral orifices. The valve of the apparently normal right ureter was also slightly thicker than usual. See Gruber (15), figure 3. The uretero-vesical valve which guarded the left ureter was very edematous, inflamed, and twice the width and thickness of its mate. This difference can also be seen by comparing :figure 2 which is a photomicrograph of a longitudinal section of the enlarged uretero-vesical valve and of the longitudinal section of the normal uretero-vesical valve presented by Gruber (15), figure 4. The magnification in each jnstance is the same. this animal the left ureter measured 15 mm. in diameter; the right 3 mm. There was also a marked tortuosity of the ureter. RESULTS
To prove that no obstruction existed and that the ureteral orifice was patent the ureters and bladder were attached to mercury manometers and the intra-vesical pressure increased (14). Figure 3 is the result. It will be noted that the pressure within the hydrometer, curve 4, follows the changes in intra-vesical pressure, curve 3. The right seemingly normal uretero-vesical valve was also somewhat affected. was competent to low pressures (see curve 1, fig. 3), but incompetent to higher ones. The valve permitted rapid regurgitation of fluid as soon as intra-vesical pressure passed 22 mm. of mercury1 the slight edema and thickening of the valve interfering with tight closure of the orifice. In this figure curves A and Bare same except the manometers on the ureter were interchanged
170
CHARLES M. GRUBER
to show that the manometers were both recording properly. Table 1 and the remaining figures present the findings from the animals operated on in our laboratory. In table 1 each case in which the entire uretero-vesical valve was excised and the ureters remained patent hydroureters were produced. In three instances, dogs 2, 10 and 15, complete obstruction occurred for
K.
R.
1
3
B. FIG.
5.
PHOTOMICROGRAPHS OF CROSS SECTIONS OF FERENT LEVELS
Two
URETERS AT DIF-
K., near kidney; 2, middle third; B 3, bladder end; L., left ureter; R., right ureter.
which we are unable to account in dogs 2 and 10, but which may have been due to infection. Animal 2 aborted eight days after the operation and for almost a month following the operation it was very sick. In animal 15 the occlusion can be accounted for by carelessness on the part of the operator, an assistant, who made the incision into the bladder not in the midline ventrally
F"GNCTIOK o:B' UBETERO-YESICAL VALVE
but nearer the left ureter and in closing the wound he accidentally closed also the ureteral orifice. In three instances, dogs 3, 6 and 7, only part of the uretero-vesical valyes were removed. Dogs 3 and 6 show how small an amount of the valve can be left and still be competent to normal intra-Yesical pressures and distention of the bladder walL In these no changes were noted in the ureters and vvhen tested for competency no reflux was found.
FIG.
6.
RECORD SHOWING CHANGES IN INTRA-URETEHAL PRESSURE \\'ITH CHANGES IN INTRA-VESICAL PRESSURE
This record was made with the bladder shown in figure 4, dog 5. 1, changes in pressure in millimeter of mercury of the left ureter with the valve missing; 2, horizontal line; 8, changes in intra-vesical pressure in millimeter of mercury; i, increases; 1, decreases; 4, record of the right ureter with the valve normal. Curves A and Bare alike except that the mercury manometers attached to the ureters were interchanged. It will be seen from curve 4 that the pressure within the ureter with the normal uretero-vesical valve shows no change in pressure, whereas it will be seen from curve 1 that the ureter with the valve missing follows very closely the changes in intra-vesical pressure. Reduced½-
In dog 7 a very small amount of the valve was left. It ,vas competent to low pressures (see fig. 9), but incompetent to higher pressures and, as would be expected, a hydroureter was the result of the operation. Figure 4 is an illustration showing the appearance of the trigone one hundred and sixty-nine days after operation in dog 5. this instance the left uretero-vesical valve was excised, the orifice thus remaining patent. The ureter was very much dilated as
172
CHARLES M. GRUBER
can be seen not only in figure 4 but also in the photomicrograph of cross sections in figure 5 taken from near the kidney at 1; middle third at 2; and bladder end at 3; of both the ureters. The wall of the left ureter was thin and much paler than that of the normal right. A test of the effect of changes in intra-ureteral pressures with changes in intra-vesical pressure was made in each animal. Figure 6 is a record made from animal 5; .the bladder and ureters from which are illustrated in figures 4 and 5. It will be observed in figure 6 that the pressure within the left ureter, curve 1, changes with and is the same as the pressure within the bladder, curve 3. The right ureter with the ureterovesical valve intact was competent with all pressures, curve 4The only difference in curves A and B is that the manometers in the ureters were interchanged; thus curve B confirms curve A in every respect. It will be noted as the pressure in 3 increases or decreases the pressure in 1 increases or decreases also while that in 4 remains at zero. Figure 7 is a photograph of the excised left, L, and right, R, ureters of dogs 1, 7, 8 and 9. In animals 1, 7 and 8 the left uretero-vesical valves were excised and in animal 9 the right. In each case the ureter with its valve removed shows some increase in diameter and no doubt this difference would have become more and more marked had the animals been allowed to live years instead of months following the operations. Figures 8, 9 and 10 are presented to show the presence of spontaneous anti-peristaltic and peristaltic contractions in hydroureters. Figure 8 was obtained from dog 9; a photograph of the ureter is shown in figure 7. In this curve 1 was written by the ureter from which the valve had previously been excised; 2, the time in two-second intervals; 3, changes in intra-vesical pressure; i, increase; l, decrease; and 4, changes in pressure within the ureter with the normal uretero-vesical valve. The small waves seen in 1 are anti-peristaltic, 5, and peristaltic, 6, in character, i.e., the pressure within the ureter is suddenly increased in 5 and decreased by the waves in 6. The former forcing the fluid toward the kidney end of the ureter and in the latter an attempt on the part of the ureter to empty the fluid
FUNCTION OF URETERO-VESICAL VALVE
within its lumen into the bladder. The changes in intra-vesicaJ pressures are noted on the record in curve 3.
FIG.
7.
PHOTOGRAPH TAKEN OF EXCISED URETERS FROM DOGS
1, 7, 8
AND
9
L. is left ureter; R. is the right. In dogs 1, 7 and 8 the left uretero-vesical valve was excised, in dog 9 the right. An increase in the diameter of the ureter in which the valve is cut is noted in each instance,
Fm. 8,
RECORD MADE BY BLADDER AND URETERS OF DoG
9
1 shows changes in intra-ureteral pressure in millimeters of mercury in the ureter in which the valve is missing; 2, time in two-second intervals; 3, changes in intra-vesical pressure ( 1 increases; l decreases) in millimeter of mercury, 4, record of ureter with normal valve attached. In addition to the changes in pressure in curve 1, there are seen both peristaltic, 6, and anti-peristaltic, 5, contractions. All remaining curves reduced½-
Figure 9 is a record taken from the excised bladder and ureter of dog 7 with about one-fifth of the uretero-vesical valve remain-
174
CHARLES M. GRUBER
ing. It will be observed that this small amount of tissue was able to withstand 14 mm. Hg intra-vesical pressure in A but was incompetent after the bladder was once stretched as observed in B. In this figure O and O' are ordinates written simultaneously by the writing points of the mercury manometers. Apparently as the bladder stretched, this short flap was no longer able to
FIG.
9.
RECORD ::\fADE BY CHANGES IN PRESSURE OF URETERS AND BLADDER IN Doa 7
Curve 1 is that of the ureter possessing a normal uretero-vesical valve. Curve Curve 3, changes in intra-vesical pressure in millimeters of mercury ( 1 increase; J decrease). Curve 4, changes in intra-ureteral pressure in which the valve was missing. In A it will be seen that the valve was competent to an intra-vesical pressure below 14 mm. of mercury. After the bladder was stretched the valve apparently became incompetent to much lower pressures as seen in B. 0 and O' are ordinates written simultaneously by the writing points of the mercury manometers. It will be seen in B as the bladder stretches at O' the valve suddenly permitted reflux of the bladder fluid. Both peristaltic and anti-peristaltic movement are recorded by the dilated ureter in B even for a pressure of 28 mm. of mercury. 2, time in two-second intervals.
close the ureteral orifice and reflux suddenly occurred. Upon the basis of such finding we believe the observations presented by Graves and Davidoff (9) misleading. If the bladder is distended to five times its normal capacity any passive structure such as the uretero-vesical valve will if short originally, become incompetent. Another finding in figure 9 is to be noted, i.e., the presence of peristalsis and anti-peristalsis in the hydrometer with increasing
FUNCTIOK OF URETERO-VESICAL VALVE
intra-ureteral pressure (curve 4, B). These waves exist not only with low pressures, 14 mm. of mercury, but also for the higher pressure, mm. mercury. Upon close inspection many very small contractions can be observed in curve 4, B, at this pressure. In other words the dog's ureter, certainly in this instance, is capable of lifting a column of mercury 28 mm. high. Wislocki and O'Conor (16) observed peristaltic and occasionally anti-peristaltic contractions in hydroureters when the pressure was suddenly released. In figure 10 is seen a large anti-peristaltic
FIG. 10. RECORD J\JADJD WITH BLADDER AND URETERS FROM ANIMAL 8 SHOWING REFLUX WITH ALL CHANGES OF lN"I'ItA-VESICAL PRESSURES IN THE URETER WITH THE VALVE J\JISSING
For complete explanation sec figure 9 This record shows a very strong anti-peristaltic contraction, at 10, following the lowering of the intra-urcteral pressure. 7 shows a peristaltic contraction.
contraction at 10 folknving a decrease in intra-ureteral pressure. This record was made from dog 8. in previous experiments the ureter with the valve intact shows no change in pressure, curve 1, with changes in intra-vesical pressure, curve 3, while the ureter the valve previously excised, curve 4, shows changes similar to those found in the bladder. In this animal as in animal 1 the increased intra-vesical pressure called forth a spastic contraction, peristaltic contraction, of the ureter almost sufficient to prevent its filling at 6 with a pressure of 12 mm. Hg. 'l'HE JO"GR~AL OF "GHOLOGY, YOL. XXIII, KO.
2
176
CHARLES M. GRUBER
There is a very marked delay in the filling of the ureter when compared with the pressure change at 5 in curve 3. At 7 another attempt was made by the ureter to empty itself, at which time a contraction wave swept over the ureter toward the bladder. As the pressure was increased the contractions disappeared entirely to reappear with full force when the pressure was reduced. DISCUSSION
At first glance our results do not seem to agree with the negative results noted by Draper and Braasch (11) in similar experiments. If, however, we consider more closely all the facts it is quite possible to account for the differences. Draper and Braasch found a dilated ureter in 1 animal in which the ureterovesical valve had been cut one hundred and sixty-three days previously. Most of their animals were killed too soon after their operations to have permitted much change to occur in the ureter as a result of the back flow of urine. This is especially true for the females in which the urethra is short and large permitting the emptying of the bladder with little increased intravesical pressure. In male dogs in which the urethra is narrow, curved and long we observed dilatation of the ureter two months after the uretero-vesical valve was cut as great as that found in females after five months. The question of whether or not the above authors excised the entire intra-vesical ureter and left the ureteral orifice really open is also important. We found at autopsy that in three of our animals parts of the valves remained. These were short, about one-third, one-fourth and one-fifth the length of the opposite normal intra-vesical ureter. The last in a male dog, in which the urethra was naturally long and narrow was competent to low pressures but not to high ones; thus requiring considerable increase in intra-vesical pressure to expel the urine from the bladder during each period of voiding. During voiding, at least, reflux of urine from the bladder into the ureter probably occurred, so that the pressure within the ureter was the same as that within the bladder. In the other two animals, both females, this reflux ·with increased intra-ureteral pressure did not occur because of the more competent valve and lower
FUNCTION OF URETERO-VESICAL VALVE
resistance to the passage of urine through the urethra consequent lower intra-vesical pressure during the act of voiding. From our findings in these animals we concur with Draper and Braasch (11) that in experienced hands there is probably little danger in human beings from the operation of meatotomy through the operative cystoscope either in regard to immediate hemorrhage, sepsis or late results from injury to the ureter and kidney as it appears very unlikely that the entire valve will be cut this procedure. Dogs 3 and 6 show very clearly that the complete removal of two-thirds to three-fourths of the valve does not necessarily incapacitate the valve to low or even normal intravesical pressures. With the aid of the intramural ureter, the oblique passage of the ureter through the thick bladder wall in human beings, the uretero-vesical valve remaining after meatotomy would probably maintain its competency. No one seems to have reported the development of a hydroureter or a hydronephrosis following meatotomy for the removal of stones in the ureter. Our results present a possible explanation of the cause of the hydroureters and hydronephrosis now classed as congenital although found in elderly people. Any condition which renders the uretero-vesical valve less elastic and less flexible would prevent closing completely and reflux vrnuld occur. Thickening of the valve by an inflammatory process or by edema may temporarily permit reflux which would if continued a sufficiently long time lead to the production of an hydrometer and even hydronephrosis. Although should the condition of the val"rn become improved the damage would remain to be found later and classed as a congenital anomaly. These findings are in accord with those of Hagner (I 7) and Gayet and Rousset (18). The activity of the ureter does not seem to be altered by its dilatation. Spontaneous peristalsis and anti-peristalsis were both noted. In the beginning the ureters apparently attempt to compensate for the defective valve mechanism. Spasms of ureter as a result of back flow are common. As the ureter becomes more and more dilated this protective mechanism the spasm is apparently lost. The fact that anti-peristalsis ,vas found
178
CHARLES M. GRUBER
in these ureters would lead us to believe that ascending renal infections could be readily produced by infecting the urine in the bladder. This question is being investigated at present in this laboratory. SUMMARY
1. Excision of the uretero-vesical valve, intra-vesical ureter,
in dogs leads to he production of an hydrometer. 2. Removal of two-thirds to three-fourths of the intra-vesical ureter does not render it incompetent to normal intra-vesical pressure changes. 3. Two hydrometers in pigs were studied, in which no obstruction was noted, the valves were found to be edematous and incompetent. 4. No change in the activity of the ureter was noted through progressive dilatation. Both peristaltic and anti-peristaltic contractions were observed. 5. In this series the maximal pressure lifted by the ureter during contraction was 28 mm. of mercury. 6. Meatotomy in human beings performed with the operative cystoscope is probably a safe procedure. REFERENCES (1) HINMAN AND MORISON: Surg., Gynecol. and Obstet., 1926, xlii, 207. WISLOCKI AND O'CoNoR: Johns Hopkins Hosp. Bull., 1920, xxxi, 352; Proc. Amer. Jour. Physiol., 1921, lv, 316. PENFIELD: Amer. Jour. Med. Sci., 1921, clx, 36. JONES: Jour. Obstet., 1914, lxx, 329. ScoTT: Surg., Gynecol. and Obstet., 1912, xv, 296. KEITH AND PULFORD: Arch. Int. Med., 1917, xx, 853. KAWASOYE: Zeitschr. f. Gynak. Urol., 1911-12, iii, 172; and others. (2) YouNG: Practice of Urology, 1926. CARSON: Jour. Urol., 1927, xvii, 61; Amer. Jour. Surg., 1927, iii, 541; and others. (3) DRAnm AND BRAASCH: Jour. Amer. Med. Assoc., 1913, lx, 20. ANDLER: Zeitschr. f. Urol. Chir., 1925, xvii, 298. STEWART AND BARBER: Ann. Surg., 1914, lx, 723. (4) ALBARRAN AND LEGUEU: Ann. d. Mal. d. Org. Genito-Urin., 1892, x, 407. BARBEY: Zeitschr. f. Urol. Chir., 1913, i, 577. PAPIN: Encyclopedie Francoise d'Urologie, 1914. PAPIN AND LEGUEU: Arch. Urol. d. 1. chin. d. Necher, i, no. 4.
:FUNCTION OF URETERO-VESICAL VALVE
(5) (6) (7) (8) (9) (10)
(ll) (12) (13)
(14) (15) (16) (17) (18) (19)
179
KRETSCHMER AND GREER: Surg., Gynecol. and Obstet., HJ15, xxi, 228. HEPBURN: Surg., Gynccol. and Obstet., 1919, xxviii, 316. LAURIE" Jour. Urol., 1922, viii, 491. VoN LrcHLEKBERG: Zeitschr. f. Urol., 1924, xviii, 592. OcKERBLAD: Jour. Urol., 1925, xiii, 325. KESSLER: Radiology, 1925, v, 163. EISENDRATH, KATZ AND GLASSER: Jour. M.ed. Assoc., 1925, 1121 G0'.1.'TLrnB: Zeitschr. f. Urol., 1926, xx, 161. SARGI"K"r: Jour. Urol., 1926, xvi, 23. RAVASINI: Reform a 1\!fed., 1926, xlii, 1117. GRAN'.l': Jour. Urol., 1926, xvi, 137. LEwrs: Jour. Urol., 1926, xv, 189. ANDRE Rev. Med. d. l'est, 1926, !iv, 769. DILLON: Calif. West Med., 1927, xxvi, 72. AIEVOLI: Gazz. internaz Med. Chir., 1927, xxxii, 1. DEROCHE AND CHEVALIER: Bull. Soc. Franc. d.'Urol., 1927, vi, 52; Jour. d'Urol., 1927, xxiii, 158. CAULK: Jour. Urol., 1923, ix, 315. EISENSTAEDT: Jour. Urol., 1926, xv, 21; Arch. Surg., 1926, 64. AnwoLI: Reform a Med., 1925, xli, 971. Y ou1rn: Practice of Urology, 1926, i, 19. SAMPSON: Johns Hopkins Hosp. Bull., 1903, xiv, 334. GRAVES AND DAVIDOFF: Jour. Urol., 1923, x, 184; ibid., 1925, xiv, 1. CouRTADE AND GUYON: Le cons cliniques sur les Maladies des voies Uri-naires; reviewed by YouNG: Johns Hopkins Hosp. Bull., 1898, ix_. 105; cited by GRAVES AND DAVIDOFF: Loe. cit. DRAPER AND BRAASCH: Jour. Amer. Med. Assoc., 1913, Ix, 20. STEWART AND BARBER: Ann. Surg., 1914, Ix, 723. AKDLIDR: Zeitschr. f. Urolog. Chir., 1925, xvii, 298; reviewed in Jour. Amer. Med., Assoc., 1925, lxxxv, 235. GRUBrnR: J our. U rol. (article II). GRUBER: Jour. Urol. (article I). WISLOCKI AND O'CoNoR: Johns Hopkins Hosp. Bull., 1920, xxxi, 352; Proc. Amer. Jour. Physiol., 1921, lv, 316. HAGNER: Surg., Gynecol. and Obstet., 1912, xv, 510. GAYIDT AND RoussET: Jour. d.'Urol. 1924, xvii, 97; reviewed in ,four. Amer. ~\1ed. 1924, lxxxii, 1482. Young, H. H.: Hydraulic pressure in genito-urinary practice, especially in contracture of the bladder, Johns Hopkins Bulletin 1898, vol. pages 100-113.
The production of hydroureters with partial or complete obstruction of the ureter is a common observation both experimentally (1) and clinically (2) but the experimental production of a hydrometer without obstruction has been observed in a instances only. In these isolated cases the authors believed some spasm of the ureter or other partial obstructive process of injury was their cause (3). Congenital hydrometers of which the uretero-vesical valves are found to be incompetent and the ureteral orifices patent have been described (4) frequently in the clinical literature. In many instances, however, these ureters were first discovered in the patient after middle age and because no obstruction was noted at the time of observation and no history of such a tion in these patients could be obtained, the ureters were regarded as congenital. Caulk (5) was the first to describe a congenital "megaloureter'' patent uretero-vesical orifices. Since his description many ureters which had previously been classed as hydroureters are now reclassed as megalo-ureters (6). Young (7) observed a single instance of a hydroureter in which the ureterovesical valve was incompetent, and in which no obstruction was noted. He believed that the dilated ureter was the result of some obstruction, either a spasm or a stone, which had disappeared but had left the ureter permanently darn.aged. Sampson (8) after injuring the mucosa of the ureteral orifices noted no increase in the regurgitation of fluids from the bladder 161 THE JOURNAL OF' UROLOGY 1 YOL. XXIII 1 KO.
2
162
CHARLES M. GRUBER
into the ureters. His findings were confirmed by Graves and Davidoff (9). On the other hand Courtade and Guyon (10) noted an increase in the number of regurgitations in dogs when they cut the "straps" to the uretero-vesical orifices. In a series of ten dogs, 3 females and 7 males, Draper and Braasch (11) studied the function of the uretero-vesical valve and the advisability of performing meatotomy in human beings. In these dogs one uretero-vesical valve was cut; the other was left intact. Thirty-four to one hundred and sixty-three days later the animals were killed and the ureters investigated. A hydrometer on the operated side was found in one instance only, in the dog killed one hundred and sixty-three days following the operation. Since they observed no changes in nine other animals, similarly treated, they believed the hydrometer in this single case to be caused by something other than the patent orifice. Their article does not say whether or not examinations were made of the condition of the uretero-vesical valves nor of their competency at autopsy. They tentatively concluded that in experienced hands there is little or no danger to human beings of immediate hemorrhage, sepsis or later injury to the kidney, from the operation of meatotomy through the operative cystoscope. The experiments were repeated with some modifications by Stewart and Barber (12). In addition to cutting the ureterovesical valve they stripped the ureter of all nerve, vessel and fascial connections. In these animals they observed urinary stasis and kidney distention in 66 per cent of the cases. Andler (13) believed it possible to produce hydrometers in animals by denervating the kidney and ureter without the necessity of cutting the uretero-vesical valve. Recently Gruber (14) studied the function of the ureterovesical valve and noted excision of the valve to cause the ureter to assume at all times the same pressure as that within the bladder. Since no proof of the cause of these various sporadic cases of hydrometer with patent orifice and without apparent obstruction has been given, the possibility that the increased pressure within the ureter was the cause of the hydrometer seemed a plausible theory.
FUNCTION OF URETERO-YESICAL YALYE
163
METHOD
Sixteen dogs and 2 cats were operated on under complete ether anesthesia with aseptic precautions. The bladder was ap-
Fm. 1.
DRAWING OF SECTION OF A PIG'S BLADDER SHOWING LEFT HYDROURETER AND LARGE INFLAMED EDEMATOUS lNTRA-VE8ICAL URETER OR URETEROVESICAL VALVE
Left ureter measured 15 mm. in diameter; right 3 mm. Left uretero-vesical valve twice the width and thickness of the right. All parts drawn to scale, magnification X 2. R.U., right ureter; L.U., left ureter; B., dorsal surface of bladder wall toward the dome; I.JYI.U., intra-mural ureter; I. V.U., intra-vesical ureter or ureterovesical valve; U.O., ureteral orifice; T., Bell's muscle and trigone; U., urethra.
164
CHARLES M. GRUBER
proached by a mid-lower abdominal incision in females and lateral incision in males. The bladder was brought out as gently
FIG.
2. PHOTOMICROGRAPH OF A LONGITUDINAL SECTION TAKEN THROUGH THE LEFT URETER, BLADDER AND URETERO-VESICAL VALVE OF BLADDER ILLUSTRATED IN FIGURE 1
B., bladder wall; U., ureter; I.M.U., intra-mural ureter; I.V.U., intra-vesical ureter or uretero-vesical valve., U.O., ureteral orifice. Note the thickness of valve here pictured and that of the normal pig valve illustrated by Gruber (15), figure_3. Magnification X 5.6.
Fm.
3. RECORD SHOWING CHANGES IN PRESSURE IN JVIILLIMETERS OF MERCURY w·ITHIN THE URETERS WITH CHANGES IN PRESSURE WITHIN THE BLADDER PICTURED IN FIGURE 1
1, changes in pressure within the apparently normal right ureter; 2, Horizontal line; 3, changes in intra-vesical pressure: i, increases; -l , decreases; 4, changes in pressure within the hydro-ureter with megelo-uretero-vesical valve. A and B the same except for interchanging the manometer attached to the ureters. Valve 1 competent for low pressures only; valve 4 incompetent to all changes in intra-vesical pressures. Reduced½-
as possible avoiding trauma and opened by a median ventral incision, parallel with the long axis. The operative wound was
FUNC'l'ION OF URETERO-VESICAL VALVE
165
about 2 cm. in length having its point of origin well toward the neck the bladder. The viscus was then evaginated on the operator's index finger which was applied to the dorsal surface. By this procedure the ureteric slits were usually brought plain view. A small probe was passed into one of the
FIG. 4. DRAWING OF POR'.1'ION OF BLADDER OF DOG 5, TABLE l uretern-vesical valve was excised 169 days before the animal was killed. All parts drawn to scale, magnification X 2. Left ureter measured 5 mm. in diameter; that of the right 2.5 mm. Left valve completely missing and ureter orifice patent. No obstruction or partial obstruction noted. R.U., right ureter; L.U., left ureter; B., bladder wall ventral aspect of dorsal surface; I.lvl.U., intra-mural ureter; I.V.U., intra-vesical ureter; U.O., ureteral orifice; X, scar of excised valve; 'T., trigone with Bell's muscle; U., urethra; P., verumontanum. 1Left
vesical ureters, usually the left, and with a small pair of slender bladed scissors the ventral half of the valve was excised. The bladder wall was tightly closed with three layers of sutures the abdominal wound was also closed without drainage. this ~n,wrl'" not a single instance of fistula occurred.
TABLE 1
Showing the effect of cutting the uretero-vesical valve in dogs 'upon the cross-secl'ion of 'it.s "Ureter ns coin pared to that of the other with the 'intact valve
""0
DATE
"' "'.,, "":a
"'~z )l
OF
".,, z -"'-
-1
~
OPERA-
TION
URETEROVESICAL
VALVE CUT
ANIMAL KILLED
APPEARANCE OF URETERAL ORIFICE AT AUTOPSY
Left
w
Right
---
9
6/21/27 Left
2
9
6/23/27* Left
3
9
6/27/27
Left
4
9
6/27/27
Left
12/19/27
5
ci'
6/28/27
Left
6
9
7/ 7/27
Left
2/ 4/28 Valve missing; no Normal obstruction. Orifice patent 12/19/27
CHANGES IN INTRA-URETERAL PRESSURE WITH CHANGES IN INTRA-VERICAL PRESSURE
Left
Right
Reflux with all increuserl pressnres
Valve competent. No change
Valve n1issing; complete obstruction
Normal
0
1/10/28t One-fourth of valve; re1naining valve competent. Noob· struction
Nonnal
Valve missing. Orifice patent. No obstruction
12/14/27
Valve missing. Orifice patent. No obstruction
12/19/27
One-third of valve Normal remaining; valve competent. No obstruction
COKDI'l'IOI\~ 01•' UHE1'EH AT AU1'0PSY
Left
Right Left ---Dilated hy- Normal Pelvis clilate(l clroureter
Right ____ >J'ormal
Valve c01n- Enormously Normal petent. dilated hyNo change droureter
Twice the nor- Normal mal size. Complete atrophy and absorption of kidney tissue
Valve competent to withstand 60 n1m. Hg pressure
Valve corn_- Nonnal petent. ~o chang:e
Nornial
Norrnal
Normnl
Normal
Reflux with all increases in pressure
Valve com- Dilated hypetent. droureter No change
Normal
Nonnal
Normal
Normal
Reflux with all increases in pressure
Valve con1- Dilated hypetent. droureter No change
Norrnal
Pel vis dilated
Norma!
Nonnal
Nonnal
Normal
>--"
°'°'
CONDITIO~ OF' KIDNJ
Valve competent Valve com- Norrnal to withstand all petent. increases in No change pressures tested
,
7
c:J' 12/28/27
Left
2/13/28
One-fifth of valve Normal remaining. No obstruction. Regurgitation upon compressing bladder contents
Valve competent Valve com- Dilated hyto pressures bepetent. droureter low 14 mm. Hg. No change Reflux with all pressures above
Normal
Normal
Normal
8
c:J' 12/28/27
Left
2/11/28
Valve missing. Ureter patent. No obstruction
Normal
Reflux with all increases in pressure
Normal
Pelvis dilated
Normal
9
c:J' 12/29/27
Right
2/13/28
Normal
Valve miss- Valve competent. Reflux with ing. UreNo change inall ter patent. creased No obpressures struction
Normal
Dilated hydro-
Normal
Normal
Megaloureter
Valve com- Dilated hypetent. droureter No change
ureter
10
c:J'
2/27/28
Left
5/ 3/28
Valve missing. Complete obstructio~ of ureter
Normal
11
c:J'
2/27/28
Right
5/ 3/28
Normal
Valve missing. No obstruction
Valve competent. Reflux with Normal No change all increased h1travesical pressures
Slightly Normal dilated
Normal
12
c:J'
3/ 3/28
Right
3/20/28t Normal
Valve missing. No obstruction
Valve competent. Reflux with Normal No change inall creased intravesical
Slightly
Normal
Norn1al
Normal
Normal
>-'
~
0
Valves competent. No changes
Normal
Fibrosed small Slight kidney hypertrophy
larger
than left (?)
pressures
13
c:J'
3/ 3/28
Left
5/ 4/28
Valve missing. Normal No obstruction
' Animal aborted on the eighth day after operation. t Animal died of pneumonia.
Reflux with all increases in pressure
Valve com- Slightly dipetent. lated No change!
Normal
TABLE ]--Continued
'"0 DATE
C,
""" '"~
01<'
~ ~
8~
OPERA-
el
'HON
~ z -- -14 ci' 3/ 5/28
URE'l'EllOVESICA.L VALVE CUT
Right
ANB-IAL KILLED
APPEARANCE OF URETERAL ORIFICE AT AUTOPSY
Left --5/ 3/28 Nonnal
15
ci'
3/ 5/28
Left. Opera- 3/22/2St Bladder wound healed. Compertion plete obstrucformed by tion an assistant, J. H. R Ureter incorporated in bladder walJ wound in sewing up bladder
16
ci'
3/ 5/28
Left
~
5/ 4/28
Valve missing. very Orifice small. Partial obstruction
Right Valve missing. No obstruction
CHANGES IN INTRA-URETERAL PRESSURE WITH CHANGES IN INTRA-VESICAL PRESSURE
Left
Right
Valve competent. Reflux with inNo change all creases in pressure
Norn1al
0
Normal
Reflux with high pressures
COND!'l'"ION OF' UR.lGTEH AT AUTOPSY
Left Normal
Left Right ---Slightly Norrnal dilated
Valve com- Enormously Norrnal dilated hypetent. No change droureter
Valve com- Marked dipetent. latation No change
CONDITION OF KIDSEY
Normal
Right --Normal
One and onethird times normal size. Some atrophy of kidney substance hydronephrosis
Slight hype troph y
Normal
Normal
FUNCTION OF URETERO-VESICAL VALVE
169
a period of time varying in the different cases from forty-five to two hundred and twenty-eight days after the operation the animals were anesthetized with ether; the abdomen opened and the bladder, ureters and kidneys studied while the animals were still living. The animals were then killed and the method of investigation from then on was the same as that described in previous communications (14 and 15). In addition to the animals operated on we were fortunate in obtaining two pig bladders with hydroureters attached. In both cases no obstruction was found. Both uretero-vesical valves appeared intact (see fig. 1), but there was considerable inflammation and edema of the ureteral orifices. The valve of the apparently normal right ureter was also slightly thicker than usual. See Gruber (15), figure 3. The uretero-vesical valve which guarded the left ureter was very edematous, inflamed, and twice the width and thickness of its mate. This difference can also be seen by comparing :figure 2 which is a photomicrograph of a longitudinal section of the enlarged uretero-vesical valve and of the longitudinal section of the normal uretero-vesical valve presented by Gruber (15), figure 4. The magnification in each jnstance is the same. this animal the left ureter measured 15 mm. in diameter; the right 3 mm. There was also a marked tortuosity of the ureter. RESULTS
To prove that no obstruction existed and that the ureteral orifice was patent the ureters and bladder were attached to mercury manometers and the intra-vesical pressure increased (14). Figure 3 is the result. It will be noted that the pressure within the hydrometer, curve 4, follows the changes in intra-vesical pressure, curve 3. The right seemingly normal uretero-vesical valve was also somewhat affected. was competent to low pressures (see curve 1, fig. 3), but incompetent to higher ones. The valve permitted rapid regurgitation of fluid as soon as intra-vesical pressure passed 22 mm. of mercury1 the slight edema and thickening of the valve interfering with tight closure of the orifice. In this figure curves A and Bare same except the manometers on the ureter were interchanged
170
CHARLES M. GRUBER
to show that the manometers were both recording properly. Table 1 and the remaining figures present the findings from the animals operated on in our laboratory. In table 1 each case in which the entire uretero-vesical valve was excised and the ureters remained patent hydroureters were produced. In three instances, dogs 2, 10 and 15, complete obstruction occurred for
K.
R.
1
3
B. FIG.
5.
PHOTOMICROGRAPHS OF CROSS SECTIONS OF FERENT LEVELS
Two
URETERS AT DIF-
K., near kidney; 2, middle third; B 3, bladder end; L., left ureter; R., right ureter.
which we are unable to account in dogs 2 and 10, but which may have been due to infection. Animal 2 aborted eight days after the operation and for almost a month following the operation it was very sick. In animal 15 the occlusion can be accounted for by carelessness on the part of the operator, an assistant, who made the incision into the bladder not in the midline ventrally
F"GNCTIOK o:B' UBETERO-YESICAL VALVE
but nearer the left ureter and in closing the wound he accidentally closed also the ureteral orifice. In three instances, dogs 3, 6 and 7, only part of the uretero-vesical valyes were removed. Dogs 3 and 6 show how small an amount of the valve can be left and still be competent to normal intra-Yesical pressures and distention of the bladder walL In these no changes were noted in the ureters and vvhen tested for competency no reflux was found.
FIG.
6.
RECORD SHOWING CHANGES IN INTRA-URETEHAL PRESSURE \\'ITH CHANGES IN INTRA-VESICAL PRESSURE
This record was made with the bladder shown in figure 4, dog 5. 1, changes in pressure in millimeter of mercury of the left ureter with the valve missing; 2, horizontal line; 8, changes in intra-vesical pressure in millimeter of mercury; i, increases; 1, decreases; 4, record of the right ureter with the valve normal. Curves A and Bare alike except that the mercury manometers attached to the ureters were interchanged. It will be seen from curve 4 that the pressure within the ureter with the normal uretero-vesical valve shows no change in pressure, whereas it will be seen from curve 1 that the ureter with the valve missing follows very closely the changes in intra-vesical pressure. Reduced½-
In dog 7 a very small amount of the valve was left. It ,vas competent to low pressures (see fig. 9), but incompetent to higher pressures and, as would be expected, a hydroureter was the result of the operation. Figure 4 is an illustration showing the appearance of the trigone one hundred and sixty-nine days after operation in dog 5. this instance the left uretero-vesical valve was excised, the orifice thus remaining patent. The ureter was very much dilated as
172
CHARLES M. GRUBER
can be seen not only in figure 4 but also in the photomicrograph of cross sections in figure 5 taken from near the kidney at 1; middle third at 2; and bladder end at 3; of both the ureters. The wall of the left ureter was thin and much paler than that of the normal right. A test of the effect of changes in intra-ureteral pressures with changes in intra-vesical pressure was made in each animal. Figure 6 is a record made from animal 5; .the bladder and ureters from which are illustrated in figures 4 and 5. It will be observed in figure 6 that the pressure within the left ureter, curve 1, changes with and is the same as the pressure within the bladder, curve 3. The right ureter with the ureterovesical valve intact was competent with all pressures, curve 4The only difference in curves A and B is that the manometers in the ureters were interchanged; thus curve B confirms curve A in every respect. It will be noted as the pressure in 3 increases or decreases the pressure in 1 increases or decreases also while that in 4 remains at zero. Figure 7 is a photograph of the excised left, L, and right, R, ureters of dogs 1, 7, 8 and 9. In animals 1, 7 and 8 the left uretero-vesical valves were excised and in animal 9 the right. In each case the ureter with its valve removed shows some increase in diameter and no doubt this difference would have become more and more marked had the animals been allowed to live years instead of months following the operations. Figures 8, 9 and 10 are presented to show the presence of spontaneous anti-peristaltic and peristaltic contractions in hydroureters. Figure 8 was obtained from dog 9; a photograph of the ureter is shown in figure 7. In this curve 1 was written by the ureter from which the valve had previously been excised; 2, the time in two-second intervals; 3, changes in intra-vesical pressure; i, increase; l, decrease; and 4, changes in pressure within the ureter with the normal uretero-vesical valve. The small waves seen in 1 are anti-peristaltic, 5, and peristaltic, 6, in character, i.e., the pressure within the ureter is suddenly increased in 5 and decreased by the waves in 6. The former forcing the fluid toward the kidney end of the ureter and in the latter an attempt on the part of the ureter to empty the fluid
FUNCTION OF URETERO-VESICAL VALVE
within its lumen into the bladder. The changes in intra-vesicaJ pressures are noted on the record in curve 3.
FIG.
7.
PHOTOGRAPH TAKEN OF EXCISED URETERS FROM DOGS
1, 7, 8
AND
9
L. is left ureter; R. is the right. In dogs 1, 7 and 8 the left uretero-vesical valve was excised, in dog 9 the right. An increase in the diameter of the ureter in which the valve is cut is noted in each instance,
Fm. 8,
RECORD MADE BY BLADDER AND URETERS OF DoG
9
1 shows changes in intra-ureteral pressure in millimeters of mercury in the ureter in which the valve is missing; 2, time in two-second intervals; 3, changes in intra-vesical pressure ( 1 increases; l decreases) in millimeter of mercury, 4, record of ureter with normal valve attached. In addition to the changes in pressure in curve 1, there are seen both peristaltic, 6, and anti-peristaltic, 5, contractions. All remaining curves reduced½-
Figure 9 is a record taken from the excised bladder and ureter of dog 7 with about one-fifth of the uretero-vesical valve remain-
174
CHARLES M. GRUBER
ing. It will be observed that this small amount of tissue was able to withstand 14 mm. Hg intra-vesical pressure in A but was incompetent after the bladder was once stretched as observed in B. In this figure O and O' are ordinates written simultaneously by the writing points of the mercury manometers. Apparently as the bladder stretched, this short flap was no longer able to
FIG.
9.
RECORD ::\fADE BY CHANGES IN PRESSURE OF URETERS AND BLADDER IN Doa 7
Curve 1 is that of the ureter possessing a normal uretero-vesical valve. Curve Curve 3, changes in intra-vesical pressure in millimeters of mercury ( 1 increase; J decrease). Curve 4, changes in intra-ureteral pressure in which the valve was missing. In A it will be seen that the valve was competent to an intra-vesical pressure below 14 mm. of mercury. After the bladder was stretched the valve apparently became incompetent to much lower pressures as seen in B. 0 and O' are ordinates written simultaneously by the writing points of the mercury manometers. It will be seen in B as the bladder stretches at O' the valve suddenly permitted reflux of the bladder fluid. Both peristaltic and anti-peristaltic movement are recorded by the dilated ureter in B even for a pressure of 28 mm. of mercury. 2, time in two-second intervals.
close the ureteral orifice and reflux suddenly occurred. Upon the basis of such finding we believe the observations presented by Graves and Davidoff (9) misleading. If the bladder is distended to five times its normal capacity any passive structure such as the uretero-vesical valve will if short originally, become incompetent. Another finding in figure 9 is to be noted, i.e., the presence of peristalsis and anti-peristalsis in the hydrometer with increasing
FUNCTIOK OF URETERO-VESICAL VALVE
intra-ureteral pressure (curve 4, B). These waves exist not only with low pressures, 14 mm. of mercury, but also for the higher pressure, mm. mercury. Upon close inspection many very small contractions can be observed in curve 4, B, at this pressure. In other words the dog's ureter, certainly in this instance, is capable of lifting a column of mercury 28 mm. high. Wislocki and O'Conor (16) observed peristaltic and occasionally anti-peristaltic contractions in hydroureters when the pressure was suddenly released. In figure 10 is seen a large anti-peristaltic
FIG. 10. RECORD J\JADJD WITH BLADDER AND URETERS FROM ANIMAL 8 SHOWING REFLUX WITH ALL CHANGES OF lN"I'ItA-VESICAL PRESSURES IN THE URETER WITH THE VALVE J\JISSING
For complete explanation sec figure 9 This record shows a very strong anti-peristaltic contraction, at 10, following the lowering of the intra-urcteral pressure. 7 shows a peristaltic contraction.
contraction at 10 folknving a decrease in intra-ureteral pressure. This record was made from dog 8. in previous experiments the ureter with the valve intact shows no change in pressure, curve 1, with changes in intra-vesical pressure, curve 3, while the ureter the valve previously excised, curve 4, shows changes similar to those found in the bladder. In this animal as in animal 1 the increased intra-vesical pressure called forth a spastic contraction, peristaltic contraction, of the ureter almost sufficient to prevent its filling at 6 with a pressure of 12 mm. Hg. 'l'HE JO"GR~AL OF "GHOLOGY, YOL. XXIII, KO.
2
176
CHARLES M. GRUBER
There is a very marked delay in the filling of the ureter when compared with the pressure change at 5 in curve 3. At 7 another attempt was made by the ureter to empty itself, at which time a contraction wave swept over the ureter toward the bladder. As the pressure was increased the contractions disappeared entirely to reappear with full force when the pressure was reduced. DISCUSSION
At first glance our results do not seem to agree with the negative results noted by Draper and Braasch (11) in similar experiments. If, however, we consider more closely all the facts it is quite possible to account for the differences. Draper and Braasch found a dilated ureter in 1 animal in which the ureterovesical valve had been cut one hundred and sixty-three days previously. Most of their animals were killed too soon after their operations to have permitted much change to occur in the ureter as a result of the back flow of urine. This is especially true for the females in which the urethra is short and large permitting the emptying of the bladder with little increased intravesical pressure. In male dogs in which the urethra is narrow, curved and long we observed dilatation of the ureter two months after the uretero-vesical valve was cut as great as that found in females after five months. The question of whether or not the above authors excised the entire intra-vesical ureter and left the ureteral orifice really open is also important. We found at autopsy that in three of our animals parts of the valves remained. These were short, about one-third, one-fourth and one-fifth the length of the opposite normal intra-vesical ureter. The last in a male dog, in which the urethra was naturally long and narrow was competent to low pressures but not to high ones; thus requiring considerable increase in intra-vesical pressure to expel the urine from the bladder during each period of voiding. During voiding, at least, reflux of urine from the bladder into the ureter probably occurred, so that the pressure within the ureter was the same as that within the bladder. In the other two animals, both females, this reflux ·with increased intra-ureteral pressure did not occur because of the more competent valve and lower
FUNCTION OF URETERO-VESICAL VALVE
resistance to the passage of urine through the urethra consequent lower intra-vesical pressure during the act of voiding. From our findings in these animals we concur with Draper and Braasch (11) that in experienced hands there is probably little danger in human beings from the operation of meatotomy through the operative cystoscope either in regard to immediate hemorrhage, sepsis or late results from injury to the ureter and kidney as it appears very unlikely that the entire valve will be cut this procedure. Dogs 3 and 6 show very clearly that the complete removal of two-thirds to three-fourths of the valve does not necessarily incapacitate the valve to low or even normal intravesical pressures. With the aid of the intramural ureter, the oblique passage of the ureter through the thick bladder wall in human beings, the uretero-vesical valve remaining after meatotomy would probably maintain its competency. No one seems to have reported the development of a hydroureter or a hydronephrosis following meatotomy for the removal of stones in the ureter. Our results present a possible explanation of the cause of the hydroureters and hydronephrosis now classed as congenital although found in elderly people. Any condition which renders the uretero-vesical valve less elastic and less flexible would prevent closing completely and reflux vrnuld occur. Thickening of the valve by an inflammatory process or by edema may temporarily permit reflux which would if continued a sufficiently long time lead to the production of an hydrometer and even hydronephrosis. Although should the condition of the val"rn become improved the damage would remain to be found later and classed as a congenital anomaly. These findings are in accord with those of Hagner (I 7) and Gayet and Rousset (18). The activity of the ureter does not seem to be altered by its dilatation. Spontaneous peristalsis and anti-peristalsis were both noted. In the beginning the ureters apparently attempt to compensate for the defective valve mechanism. Spasms of ureter as a result of back flow are common. As the ureter becomes more and more dilated this protective mechanism the spasm is apparently lost. The fact that anti-peristalsis ,vas found
178
CHARLES M. GRUBER
in these ureters would lead us to believe that ascending renal infections could be readily produced by infecting the urine in the bladder. This question is being investigated at present in this laboratory. SUMMARY
1. Excision of the uretero-vesical valve, intra-vesical ureter,
in dogs leads to he production of an hydrometer. 2. Removal of two-thirds to three-fourths of the intra-vesical ureter does not render it incompetent to normal intra-vesical pressure changes. 3. Two hydrometers in pigs were studied, in which no obstruction was noted, the valves were found to be edematous and incompetent. 4. No change in the activity of the ureter was noted through progressive dilatation. Both peristaltic and anti-peristaltic contractions were observed. 5. In this series the maximal pressure lifted by the ureter during contraction was 28 mm. of mercury. 6. Meatotomy in human beings performed with the operative cystoscope is probably a safe procedure. REFERENCES (1) HINMAN AND MORISON: Surg., Gynecol. and Obstet., 1926, xlii, 207. WISLOCKI AND O'CoNoR: Johns Hopkins Hosp. Bull., 1920, xxxi, 352; Proc. Amer. Jour. Physiol., 1921, lv, 316. PENFIELD: Amer. Jour. Med. Sci., 1921, clx, 36. JONES: Jour. Obstet., 1914, lxx, 329. ScoTT: Surg., Gynecol. and Obstet., 1912, xv, 296. KEITH AND PULFORD: Arch. Int. Med., 1917, xx, 853. KAWASOYE: Zeitschr. f. Gynak. Urol., 1911-12, iii, 172; and others. (2) YouNG: Practice of Urology, 1926. CARSON: Jour. Urol., 1927, xvii, 61; Amer. Jour. Surg., 1927, iii, 541; and others. (3) DRAnm AND BRAASCH: Jour. Amer. Med. Assoc., 1913, lx, 20. ANDLER: Zeitschr. f. Urol. Chir., 1925, xvii, 298. STEWART AND BARBER: Ann. Surg., 1914, lx, 723. (4) ALBARRAN AND LEGUEU: Ann. d. Mal. d. Org. Genito-Urin., 1892, x, 407. BARBEY: Zeitschr. f. Urol. Chir., 1913, i, 577. PAPIN: Encyclopedie Francoise d'Urologie, 1914. PAPIN AND LEGUEU: Arch. Urol. d. 1. chin. d. Necher, i, no. 4.
:FUNCTION OF URETERO-VESICAL VALVE
(5) (6) (7) (8) (9) (10)
(ll) (12) (13)
(14) (15) (16) (17) (18) (19)
179
KRETSCHMER AND GREER: Surg., Gynecol. and Obstet., HJ15, xxi, 228. HEPBURN: Surg., Gynccol. and Obstet., 1919, xxviii, 316. LAURIE" Jour. Urol., 1922, viii, 491. VoN LrcHLEKBERG: Zeitschr. f. Urol., 1924, xviii, 592. OcKERBLAD: Jour. Urol., 1925, xiii, 325. KESSLER: Radiology, 1925, v, 163. EISENDRATH, KATZ AND GLASSER: Jour. M.ed. Assoc., 1925, 1121 G0'.1.'TLrnB: Zeitschr. f. Urol., 1926, xx, 161. SARGI"K"r: Jour. Urol., 1926, xvi, 23. RAVASINI: Reform a 1\!fed., 1926, xlii, 1117. GRAN'.l': Jour. Urol., 1926, xvi, 137. LEwrs: Jour. Urol., 1926, xv, 189. ANDRE Rev. Med. d. l'est, 1926, !iv, 769. DILLON: Calif. West Med., 1927, xxvi, 72. AIEVOLI: Gazz. internaz Med. Chir., 1927, xxxii, 1. DEROCHE AND CHEVALIER: Bull. Soc. Franc. d.'Urol., 1927, vi, 52; Jour. d'Urol., 1927, xxiii, 158. CAULK: Jour. Urol., 1923, ix, 315. EISENSTAEDT: Jour. Urol., 1926, xv, 21; Arch. Surg., 1926, 64. AnwoLI: Reform a Med., 1925, xli, 971. Y ou1rn: Practice of Urology, 1926, i, 19. SAMPSON: Johns Hopkins Hosp. Bull., 1903, xiv, 334. GRAVES AND DAVIDOFF: Jour. Urol., 1923, x, 184; ibid., 1925, xiv, 1. CouRTADE AND GUYON: Le cons cliniques sur les Maladies des voies Uri-naires; reviewed by YouNG: Johns Hopkins Hosp. Bull., 1898, ix_. 105; cited by GRAVES AND DAVIDOFF: Loe. cit. DRAPER AND BRAASCH: Jour. Amer. Med. Assoc., 1913, Ix, 20. STEWART AND BARBER: Ann. Surg., 1914, Ix, 723. AKDLIDR: Zeitschr. f. Urolog. Chir., 1925, xvii, 298; reviewed in Jour. Amer. Med., Assoc., 1925, lxxxv, 235. GRUBrnR: J our. U rol. (article II). GRUBER: Jour. Urol. (article I). WISLOCKI AND O'CoNoR: Johns Hopkins Hosp. Bull., 1920, xxxi, 352; Proc. Amer. Jour. Physiol., 1921, lv, 316. HAGNER: Surg., Gynecol. and Obstet., 1912, xv, 510. GAYIDT AND RoussET: Jour. d.'Urol. 1924, xvii, 97; reviewed in ,four. Amer. ~\1ed. 1924, lxxxii, 1482. Young, H. H.: Hydraulic pressure in genito-urinary practice, especially in contracture of the bladder, Johns Hopkins Bulletin 1898, vol. pages 100-113.