The Relation Between Bladder Pressure and Urine Formation

Tni,;

JouR~AL OF UROLOGY

Yol. 74, No. 2. August Hl55 J..>rinted in U.S.A.

THE RELATIOK BETWEEN BLADDER PRESSURE AXD URINE FORMATION ROY E. TOLLS

A"iD

JAMES M. DILLE

Frum lhe Department of Pharmaeolooy, School of kledicine, University of Washington, Seattle 5, Wash.

The phenomenon of reflex amuia resulting from instrumentation of the urethra, bladder or ureters has often been noted. 1 · 2 • :i, 4 A probable anatomical pathway for such a reflex ,ms reported hy \Vharton in 1932 5 and Trueta et aL has postulated the existence of a renal shunt which would explain the intrarenal mechanism of reflex anuria or oliguria. In an effort to reproduce the shunt and the concomitant decrease in urine output, Black and Saunders, 7 using stimulated the sciatic nerve and caused a decrease in renal clearance. using rabbits, caused reflex renal suppression by a) electrical stimulation of the distal ends of sectioned nerves, b) stimulation of the central ends of these sectioned nerves, c) stimulation of vesical neck and lower ureter, produced by an electrode passed through a cystoscope. There was no recovery of function in the 15 minutes after <:essation of stimulation. Renal blood flow measurements have produced strong evidence against the existence of any intrarenal shunting of hlood such as postulated by Trueta" 1' ~ evertheless, the of urine output, produced by Black and Saunders, is eYident the refutation of the postulated intrarcnal mechanisms. This project was undertaken to demonstrate the existence of a mechanism, reflex or humoral, which inhibits urinary output. \\"hen the bladder is distended. It would seem logical to believe that there is a physiological protectin mechanimn ffhich reduces the rate of urine production when the bladder is distended. Back pressure can reduce urinary output by physical means. 10 Increased hlad
198

ROY E. TOLLS AND JAMES M. DILLE

drop counter

electrodes

! d

~~f~sion=p=,m=p~==::,I...

to manometer drop counter

drop counter

electrodes

electrodes bladder

Fm. 1. Arrangement of apparatus for measurement of urine production rate and bladder pressure recording.

There was no mechanical connection bet,veen the bladder and the kidneys. They noted that when the bladder was distended, the urine supply became inadequate and had to be supplemented. They postulated a reflex oliguria as an explanation but added that the phenomenon was not adequately substantiated by a sufficient number of observations to ,varrant its assumption as a constant occurrence. It is the purpose of this work to substantiate these incidental observations. EXPERIMENTAL METHODS

Female dogs \Vere anesthetized with 30 mg. per kg. of sodium pentothal administered intravenously. The femoral vein was cannulated and 35 mg. per kg. of chorolose was administered intravenously for prolonged anesthesia. The arrangement of the experimental apparatus is shown in figure 1. The carotid artery was cannulated for mercury manometric recording of the blood pressure on a smoked paper kymograph. A tracheal cannula was inserted to maintain a free airway. The jugular vein was cannulated for continuous intravenous infusion of saline to promote an adequate and constant urine flow. In early experiments it was found that the pressure of the distended bladder upon the hypogastric veins sometimes seemed to slow the rate of the intravenous infusion into the femoral vein cannula, so the jugular vein ,vas used. Saline from the infusion bottle passed through a chamber fitted with electrodes connected to an electronic drop counter which in turn registered each drop on the kymograph record so as to verify the constancy of the infusion rate.

RELATION BETWEEN BLADDER PRESSURE AND URINE FORMATION

199

A midline suprapubic incision was made into the peritoneal cavity and the ureters located and dissected free about three centimeters from the bladder. Polyethylene No. 90 tubing (O.D. 1.27 mm.) was used to cannulate the ureters proximally. These were advanced freely until slight resistance was noted, presumably within the renal pelvis, then they were ligated in place securely. The free ends of the tubing were led out through stab wounds in each lower quadrant. The ends of the ligatures were also pulled through the punctures and fastened under slight tension to the skin, using hemostats. This served to keep the ureters and tubing from kinking, providing free and regular urine flow to the drop counter electrodes. The output of each kidney was thus recorded on the kymograph. The bladder was then cannulated with the same size tubing inserted through the distal stumps of the ureters. One of these was connected to a 50 cc syringe of a Merck infusion pump set to deliver 3.25 cc per min. of physiological saline into the bladder. The other catheter was connected to a mercury manometer which registered upon the kymograph record the pressure within the bladder. The urethra was not disturbed and the bladder handled as little as possible, and then only with warm saline-moistened sponges. The wound was closed with towel clips and the bladder cannulae were led through the craniad end of the incision. Thus there was a preparation with no hydraulic connection between the kidney and bladder through which back pressure might be exerted. The bladder could be slowly filled at a steady rate by the infusion pump. The urethra was uninterrupted and free to pass fluid should the pressure become grossly unphysiological. In some cases micturation occurred, in others there was slow leakage. A constant intravenous saline infusion could be maintained at a rate to produce between 15 and 25 drops per minute urine output during the control periods. This infusion rate was recorded on the kymograph record. The output of each kidney was recorded in drops per minute. RESULTS

A total of 13 dogs was used in these experiments. Practically all of them showed grossly that there was relationship between intravesical pressure and production of urine by the kidney. Technical difficulties in recording made it TABLE

1. Summary of experiments

Control Period

Experimental Period

Recovery Period

mm. Mean drops/minutes Mean drops/minutes mm. mm. mm. Hg. Hg. Hg. Hg. Blood Blood Bladder Blood Right Right Right Left Left presLeft Total pressure pressure ureter ureter Total pressure ureter ureter Total ureter ureter sure - - - - - - - - ---- - - - - - - - - - - - - - - - -Animal Number

2 4 Sa b

9 11 13

Mean drops/minutes

5.3 6.0 12.3 11.4 6.1 14.1 6.8

6.1 10.2 10.0 9.6 10.6 16.2 5.1

11.4 16.2 22.3 21.0 16.7 30.3 11.9

138 130 134 140 142 110 124

48.0 40.0 26.0 29.5 16.3 16.1 28.5

3.6 3.0 6.0 8.9 4.0 13.0 3.9

5.8 5.0 4.3 6.9 4.6 11.9 3.4

9.4 8.0 10.3 15.8 8.6 24.9 7.3

141 132 168 164 158 110 123

5.8 4.0 11.4 12.0 5.2 22.2 4.7

6.2 6.0 9.6 8.6 6.4 20.0 3.6

12.0 10.0 21.0 20.6 11.6 42.2 8.3

139 132 133 165 152 110 136

200 TABLE

ROY E. TOLLS AND JAMES M. DILLE

2. Student "t" test analysis of experiment 13, comparing urine outputs in the control,

experimental and recovery periods s

Period

n

y2

Control. ....................... . Experimental. ...................... . Recovery .................. .

20

38.69 103.83

2.04 2.25

8.27

1.21

47 30

1.43 1.5 1.1

n = number of determinations y = difference of determination from mean S2 = sample variance S = standard deviation Comparison

''t''

Control to experimental. ................... ......... Experimental to recovery ............ . . . . . . . .........

11.64 33.40

Degrees of freedom --

65 75

p

less than .001 less than .001

P = probability that these data would be obtained without some factor inhibiting urinary output during experimental period.

FIG. 2. Sections from continuous kymograph recording showing relation between bladder pressure and production of urine by each kidney. A, control period. B, effect of raising bladder pressure. C, restoration to approximately situation of control period. D and E, results of second increase in bladder pressure and recovery.

difficult to use all of these experiments in the compilation of statistical results, hence table 1 shows data derived from six experiments. A typical record is shown in figure 2. This represents two experiments on the same animal. After a control period during which the flow from the right and left ureter was fairly constant, the bladder pressure was raised slowly as indicated in part B of figure 2 with a corresponding diminishment in urine flow from both ureters. Restoration of the bladder to zero pressure resulted in a return of urine production of each kidney

RELATION BETWEEN BLADDER PRESSURE AND URINE FORMATION

201

to approximately normal. After this recovery the bladder pressure was again raised as shown in part D with a corresponding decrease in urine formation. Recovery of kidney urine production was again brought about the restoration of zero bladder pressure as indicated in section E of figure 2. Table 1 is a summary of the data from the kymograph records of seven experiments. Exploratory statistical evaluation of the data showed significant differences between the control period and the experimental period. The least marked change was found in animal 13 and thiR was subjected to RtatiRtical treatment which is summarized in table 2. DISCUSSION

These experiments establish a definite relationship between the intravesical pressure and the production of urine by the kidneys. Conditions of these experiments were as nearly physiological as could be accomplished. It was possible with experience in setting up the preparation to keep trauma at an absolute minimum. The anatomical structures of the bladder were interfered with practically not at all and the region of the trigone was untouched. Hence micturition reflexes were undisturbed. The chorolose anesthesia interfered with reflex function to a minimum and had the advantage of abolishing artefacts from skeletal muscular contraction. The introduction of saline into the bladder through the ureters at a slow but constant rate reproduced physiological conditions. This preparation is, therefore, very different from that of other authors1 , 2 , 3 , 4 in which the lower urinary tract was stimulated unphysiologically, by such means as instrumentation, trauma or electrical potentials. These stimuli produce anuria but do not represent the situation in the normal animal or human. Using the experimental preparation described we believe that we have demonstrated an inverse physiological relationship between bladder pressure and urine production by the kidneys. The urine production changes by the kidney rapidly follows the bladder pressure changes and are rapidly reversed when the bladder pressure is lowered. Of interest is the relation of the blood pressure to the changes in bladder pressure. As bladder pressure increased and was sustained the blood pressure rose moderately and remained at this slightly higher level until the bladder pressure was again reduced to zero. This relation has not been explored. One might expect that it is a compensatory attempt to continue urine production since an increase in blood pressure increases urine formation. SUMMARY

A relation under physiological conditions has been shown to exist between the intravesical pressure and the production of urine by the kidneys. Increase of the intravesical pressure within physiological limits results in a decrease in urine production by the kidney.