Vol. 104, Nov. Printed in U.S.A.
THE JOURNAL OF UROLOGY
Copyright © 1970 by The Williams & Wilkins Co.
HUMAN URETERAL PERISTALSIS P. EDMOND, JAMES A. ROSS*
AND
IAN S. KIRKLAND
From the Departments of Urology and Clinical Surgery, University of Edinburgh and the Eastern and Western General Hospitals, Edinburgh, Scotland
When a ureteral catheter is linked to a pressure transducer complexes may be recorded which are considered to be produced by pressure changes in the renal pelvis and ureter consequent to muscle contraction of the wall of these structures. Such complexes give an indication of pelvic and ureteral activity and are readily reproducible. This technique has been used to study the activity of the intact human ureter and has been applied to observe the effects of drugs and of disease. 1· 2 Similar techniques have been used on experimental animals. 3- 8 Intracavital pressure recording has also been used to study patients. 9- 11 A fundamental problem has been to show that Accepted for publication December 5, 1969. * Requests for reprints: Eastern General Hospital, Seafield Road, Edinburgh, Scotland. Part of this work was supported by a grant from the Scottish Hospital Endowments Research Fund. 1 Ross, J. A., Edmond, P. and Griffiths, J.M.: The action of drugs on the intact human ureter. Brit. J. Urol., 39: 26, 1967. 2 Ross, J. A., Edmond, P. and Kirkland I. S.: Dynamic function in idiopathic hydronephrosis and hydroureter: a guide to surgical treatment. J. Roy. Coll. Surg., 13: 142, 1968. 3 Weaver, R. G. and Yelderman, J. J.: The positive pressure catheter for measurement of intracavital pressures and pressure patterns. J. Urol., 98: 718, 1968. 4 Boyarsky, S., Labay, P., Kirschner, N. and Gerber, C.: Does the ureter have nervous control? J. Urol., 97: 627, 1967. 5 Boyarsky, S., Labay, P. and Lenaghan, D.: Transureteroureterostomy, bifid ureters and ureteral dyskinesia. J. Urol., 99: 156, 1968. 6 Boya!sky, S., Labay, P. and Glenn, J. F.: More evidence for ureteral nerve function and its clinical implications. J. Urol., 99: 533 1968. 7 Grana, L., Donnelian, W. L. and sw'enson, 0.: Effect of gram-negative bacteria on ureteral structure and function. J. Urol., 99: 539, 1968. 8 Te:1gue, N. and Boyarsky, S.: Further effects of coliform bacteria on ureteral peristalsis. J. Urol., 99: 720, 1968. 9 Shalit, S. and Morales, P.: Ureteric activity in paraplegia. J. Urol., 96: 875, 1966. 10 Jose, J. S.: Idiopathic retroperitoneal fibrosis. Notes on its diagnosis, management and pathogenesis. Brit. J. Urol., 39: 431, 1967. 11 ,Strut~ers,. N. W.: T~e role of manometry in the mvest1gat10n of pelv1-ureteral function. Brit. J. Urol., 41: 129, 1969.
changes in ureteral pressure can be directly associated with evidence of the ureteral activity at the point of recording. To allow this distinction to be made it is necessary to record changes in pressure and to provide evidence of the ureteral muscle activity from the same position. Our purpose is to illustrate the behavior of the normal human ureter and to provide proof of the relationship of the pressure wave recorded to the local muscle activity of the ureter. MATERIAL AND METHODS
The technique of recording from a standard non-occlusive ureteral catheter has been used. 12 Observations have been made during routine retrograde pyelographic examinations in patients with conditions affecting the renal tract; therefore, the behavior of the normal as well as the abnormal ureter was noted. To allow simultaneous recording of local ureteral muscle action potential and pressure changes, a double platinum-electrode catheter (6F) has been substituted for the conventional ureteral catheter. In this instrument the platinum electrodes were 10 cm. apart. For some studies a second open-ended catheter was passed to the level of the lower electrode. The electrodes were connected to the electrocardiogram pre-amplifier with the normal limb leads attached. Previous observations were recorded in 52 patients with renal symptoms. 12 A further 216 patients have been studied, 67 of whom are children less than 12 years old. Analysis of results has been made from the total cases available in which the relevant period of recording has been more than 3 minutes. RESULTS IN ADULTS
Rate of contraction. The renal pelvis contracted 3 to 8 times each minute (average 4.5 per minute). This rate was altered by increasing the content 12 Ross, J. A., Edmond, P., Coull, J. and Griffiths, J.: Observations on the physiology of the human renal pelvis and ureter. J. Urol., 97:
449, 1967.
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FIG. 1. Case 6913-normal pelvic and mid ureteral contractions
FIG. 2. Case 67K04-tracing from left ureter at 5 cm. from ureterovesical junction shows triple wave
FIG. 3. Case 6923-tracings from both pelves recorded simultaneously. Contractions are not synchronous.
of the pelvis by the injection of either radiopaque solution or normal saline. The injection caused an initial but unsustained increase in rate. The rate of ureteral contraction varied from 2 to 6 per minute (average 3 per minute). As in the pelvis, injection of fluid caused an increase in rate. The rate was also influenced by antispasmodic drugs but this is a subject of special study.1 Rhythm. A marked regularity of rhythm in the contraction waves of normal pelves and ureters was noted. The usual rhythm observed in the pelvis and ureter was a single wave occurring at regular intervals (fig. 1). Double, triple and quadruple rhythms were also observed. Amplitude and form. The pelvic wave had an average amplitude of 9 cm. water (range 8 to 18 cm. water). The average duration was 4 seconds. This wave was considered to reflect pressure changes produced by both calyceal and pelvic muscular contraction. Individual calyceal contractions were occasionally measured and were smaller in amplitude than pelvic contractions. Tlie ureteral wave in the upper and middle thirds of normal ureters had an average height of 40 cm. water. The average duration was 7
seconds. The form of the contraction wave in the ureter was usually that of a single wave but in the lower third of the ureter a biphasic wave was common and occasionally a triple wave was recorded (fig. 2). Amplitude and form of contraction waves were constant-waves of the same characteristic succeeding each other with regularity. Although activity of the ureter was usually constant, in some patients who were observed for a longer period a rhythm of activity was noted-waves of greater amplitude than usual being followed by a series of smaller waves. Bilateral observations. When records are made simultaneously from both pelves or from both ureters it is seen that they do not contract synchronously (fig. 3). When a record is made from one ureter, alteration in rhythm, even to the extent of complete cessation of activity, may be produced by filling the other pelvis (fig. 4). RESULTS IN CHILDREN
Rate of contraction. The normal renal pelvis contracted on an average of 4 per minute (range 3 to 6 per minute). The rate of ureteral contractions in normal ureters varied from 2 to 5 per minute with an average of 3.7 per minute.
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Frn. 4. Case 6615. A, tracing from right ureter while left pelvis was overfilled with radiopaque solution at 30 seconds. B, activity ceased until right ureter was filled when activity restarted. Tracings were consecutive.
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Frn. 5. Case 67K09-tracing from normal ureter in 3-month-old infant. Note vigorous contractions.
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Frn. 6. Case 6732-tracings from normal right ureter simultaneously at 25 cm. and 5 cm. from ureterovesical junction. There is interval of 4 seconds between 2 points of recording 20 cm. apart.
Rhythm. The same regularity of rhythm was observed as in the adult patients. Amplitude and form. The normal pelvic wave had an average height of 9 cm. water (range 5 to 12 cm. water) with an average duration of 4 seconds. Contractions in the middle third of normal ureters had an average height of 33 cm. water (range 15 to 80 cm. water). The average duration was 6 seconds. These findings are therefore similar to those found in adult patients. Even in a 3-month-old infant contractions of an amplitude of 33 cm. water were recorded in the ureter (fig. 5).
RATE
OF
THE
PERISTALTIC
WAVE
ALONG
THE
URETER
The rate of the peristaltic wave along the ureter can be measured by recording from 2 different levels in the ureter simultaneously. Recordings taken simultaneously from ureteral catheters at 25 and at 5 cm. from the ureterovesical junction in 8 recordings showed that contraction waves had an average speed of 3.5 cm. per second (fig. 6). This speed is similar to that of the experimental animal.13- 15 13 Enhorning, G. and Weaver, R. G.: Intraureteric pressure above and below an area of
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Fm. 7. Case 68P03. A, A.C. recording at 20 cm. from ureterovesical junction (positive deflection downward). B, pressure recording from same point.
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Fm. 8. Case 6905---tracings from normal right ureter and left ureter after left nephrectomy (7 months previously) both at 10 cm. from ureterovesical junction. Left ureter contracts slowly but vigorously after filling with 5 ml. saline.
Action potentials in ureteral peristalsis. To provide evidence of local activity of the ureteral muscle as distinct from any passive change it is necessary to illustrate action potentials at the point of recording and to illustrate that these are associated with changes in pressure. Figure 7 shows that positive deflection of the record (A.C. recording) appears simultaneously with the pressure change. DISCUSSION
Indwelling catheters introduce an abnormal factor in the assessment of ureteral physiology; however, provided they are non-occlusive, they do not affect peristalsis to an appreciable extent. Under laboratory conditions indwelling catheters caused no change in renal function. 3 We believe our technique gives results which accurately reflect physiological change and is certainly less disturbing to normal physiology than any recording from an operatively exposed pelvis or compression. Amer. J. Obst. Gynec., 90: 1332, 1964. 14 Backlund, L.: Experimental studies on pressure and contractility in the ureter. Acta Physiol. Scand., (suppl. 212) 69: 1, 1963. 15 Sleater, W., Jr. and Butcher, H. R., Jr.: Action potentials and pressure changes in ureteric peristaltic waves. Amer. J. Physiol., 180: 261,
1955.
ureter or from an excised organ deprived of blood and nerve supply. The prime stimulus to ureteral contraction is the content of fluid within its lumen.1 6 The pelvis is filled by urine entering from the collecting tubules and a bolus of urine is projected by the contraction of the musculature into the ureter. This stimulates the ureter to contract and the bolus is transmitted down the ureter to the bladder by a peristaltic wave, a view previously expressed by Narath17 and Murnaghan. 18 Even when deprived of a normal bolus of urine coming from above following previous operative intervention, a healthy ureter will still contract if stimulated by direct filling. This may be demonstrated in a ureteral stump after nephrectomy (fig. 8) or prior to operation in the ureter for congenital hydronephrosis when a patho physiological block is present between pelvis and ureter. Normally pelvic contractions occur on an average of 4 to 5 times a minute with an average 16 Lapides, ,T.: The physiology of the intact human ureter. J. Urol., 59: 501, 1948, 17 N arath, P. A.: Renal pelvis and ureter. New York: Grune and Stratton, Inc., 1951. 18 Murnaghan, G. F.: The dynamics of the renal pelvis and ureter. J. Roy. Coll. Surg., 4: 157, 1959.
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elevation of 9 cm. water. Peristaltic waves occur in the ureter on an average of 3 times a minute with an elevation of 40 cm. water. The difference in the rates of pelvic and ureteral contractions indicates that not all pelvic contractions result in a subsequent ureteral contraction. Since the pelvis has the faster rate this may be or may contain the pacemaker of the system. 18 • 19 The contraction waves are regular in rhythm, amplitude and form, and travel down the ureter at an average speed of 3 to 4 cm. a second. Activity of the ureter in children is practically the same as in the adult subject. The normal rhythm observed in the pelvis and ureter is a single wave occurring at regular intervals but double, triple and quadruple rhythms may also be observed. These differences are considered to be normal variants but may also result from filling or from pathological conditions. Regularity in the normal peristaltic wave is a feature of the present series of observations. This has been questioned by Harvey and Keeling investigating pelvio-ureteral emptying by isotope renography. 20 They suggested that the peristaltic contractions in the undisturbed human renal pelvis are variable in frequency among patients and from time to time in the same subject but there is evidence that the third phase of the renogram is dependent on variations in the input of hippuran to the kidney and not on ureteral function. 21 Ureteral peristalsis is readily altered by filling the ureter which results in increased frequency of activity, and this has also been demonstrated in the experimental animal.13 Peristalsis is also rendered variable by the administration of antispasmodic drugs1 and disease processes2 but normal features under the conditions of study as described are regularity in rate, rhythm and amplitude. The form of the contraction wave is usually a single monophasic contraction in the upper and middle ureter, but in the lower third a biphasic wave is common and not infrequently a triple wave is recorded. These observations contrast with those of Struthers who stated that no special wave form could be related to a specific segment of ureter .11 In the lower ureter the first 19 Bozler, E.: Activity of pacemaker previous to discharge of muscular impulse. Amer. J. Physiol., 136: 543, 1942. 20 Harvey, R. F. and Keeling, D. H.: Investigation of ureteric function by isotope renography: with particular reference to patients with "unexplained" renal pain. Lancet, 1: 847, 1969. 21 Farmelant, M. H., Lipetz, C. A., Bikerman, V. and Burrows, B. A.: Radioisotopic renal function studies and surgical findings in 102 hypertensive patients. Amer. J. Surg., 107: 50, 1964.
elevation or peak may represent a rise in the intraluminae pressure from a contraction starting higher up the ureter, a "bolus jet wave," while the second peak results from the active contraction of the muscle at the point of recording. The somewhat different muscle pattern in the lower third of the ureter reinforced by Waldeyer's sheath may also contribute to this phenomenon. 22 • 23 Negative waves were also noted occasionally by us and by previous investigators. Negative waves may result from major changes in intraabdominal dynamics rather than from the expansive activity of ureteral muscle although Backlund has suggested that the ureter can act as a suction pump.14 This basic information on ureteral function allows consideration of the integration of function of right and left renal outflow tracts and it is evident that there is a close correlation of activity between the 2 sides. Although they do not contract synchronously, accidental overfilling of one pelvis when injecting radiopaque medium to take a radiograph produced immediate cessation of the regular contractions on the other side but activity may be regained by the stimulation of filling. This occurrence may provide a possible explanation of the reflux anuria which occurs when one ureter is stimulated by the passage of an irritating or occluding calculus. This close integration of function in the renal outflow tract is presumably mediated through the nervous system. Nerves have been shown to affect the ureteral activity in experimental animals.4· 6 With multiple channel recording, extended observation of both renal outflow tracts simultaneously becomes a possibility for routine study. SUMMARY
Observations on ureteral function in 268 patients, including 67 children, are presented. Records were taken from the normal ureter while investigation of the patient for various urological conditions was carried out by cystoscopy and retrograde pyelography. The human renal pelvis and ureter function regularly under these conditions and the intimate relationship of the pressure wave to the action potentials at the same level is illustrated. 22 Tanagho, E. A. and Pugh, R. C.: The anatomy and function of the ureterovesical junction. Brit. J. Urol., 35: 151, 1963. 2s Murnaghan, G. F.: Experimental investigation on the dynamics of the normal and dilated ureter. Brit. J. Urol., 29: 403, 1957.