INTRAMURAL URETER and URETEROCELE Alex Simpson Smith Memorial Lecture Delivered at the Hospitalfor Sick Children, London, W.C.I July 2, I963 F

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Postgrad Med J: first published as 10.1136/pgmj.40.462.179 on 1 April 1964. Downloaded from

POSTGRAD. MED. J. (I964), 40, 179

INTRAMURAL URETER AND URETEROCELE Alex Simpson Smith Memorial Lecture delivered at The Hospitalfor Sick Children, London, W.C.i July 2, I963 F. DOUGLAS STEPHENS, D.S.O., M.S.(Melbourne), F.R.A.C.S. Royal Children's Hospital Research Foundation, Melbourne, Australia

DURING the past ten years much research has been scopy lends support to this theory of action. The directed to the study of the structure and function orifice, in its resting state is a pit, slit, or falciform of the normal intramural part of the ureter. The crescentic opening. Its walls and roof are ap- anatomy of the uretero-vesical 'lock' mechanism proximated to the floor thus shutting the lumen of both the normal and abnormal variants of this from view. During expulsion of urine the ureteric part of the ureter is now more clearly understood. orifice is expanded by the force of the jet, tem- It is proposed to describe the short, the long, and porarily opening the lumen to view. After the the structurally abnormal intra-mural ureters, jet has ceased, sudden transitory contraction of together with the physiological defects which they the longitudinal muscle jerks back the rim of the involve and which provoke clinical problems. orifice, hurriedly occluding the lumen and re- setting the flap valve. The muscle then slackens The Normal Intramural Ureter to its tonic resting state. The muscle

longitudinal by copyright. The intramural ureter comprises that part of the animates and quickens the action of the flap valve. ureter which lies within the bladder from its point Moreover obstruction of the urethra causes of entry in the lateral wall to the orifice in the hypertrophy of the muscle of the intra-mural trigone. At first the ureter lies in the muscular ureter, thereby strengthening its walls and main- tunnel of the bladder and there it rests on the taining efficiency in the uretero-vesical valve. muscle of the bladder under the vesical mucosa. The severest urethral obstruction will not impair Its length is variable, being only 4 to 6 mm. long the valve action provided that this segment of the in the infant and io to i9 mm. in the adult ureter is normal in its structure. (Hutch, I962). The intramural ureter is slightly narrower in The Abnormal Intramural Ureter http://pmj.bmj.com/ calibre than the extra-vesical ureter. Its muscle Numerous defects of the intramural ureter occur coat differs in that it is composed of longitudinally and impair its function. A defective ureter may arranged muscle bundles only. The circular be too short, too long, too wide, abnormal in component of the extravesical ureter, which is its structure, or associated with a diverticulum or a most conspicuous layer, is not continued into the ureterocele. wall of the intramural ureter.

The longitudinal muscle fibres of the roof of (a) The Short Intramural Ureter on September 23, 2021 by guest. Protected the intramural ureter insert into the rim of the Absence in whole or in part of the submucosal orifice but the muscle of the floor of the ureter is segment is a common occurrence; the deficiency prolonged into the trigone, where it is tethered. is more easily recognized when it is unilateral and The function of the uretero-vesical valve, for the opposite side is available for comparison. The reasons described elsewhere, is believed to depend orifice of the short ureter issues into the bladder on an intrinsic muscular mechanism of the intra- more laterally, with result that the trigone reaches mural ureter (Stephens ana Lenaghan, I962). out towards the lateral wall of the bladder at the The eccentric tethering of the longitudinal muscle expense of the submucosal segment. Deficiency causes the roof and walls to press back upon in length of the submucosal ureter entails a cor- the floor. This action is enhanced by intra- responding reduction in its musculature and there- vesical hydrostatic pressures. The mechanism is fore in its efficiency. thus an activated flap valve, which is dependent on muscle for its activation, and obliquity of course (b) Abnormal Structure of the Intramural Ureter for its flap valve action. The formation of muscle within this segment Inspection of the orifice of the ureter at cysto- may be impaired. Defects of the muscle may take Postgrad Med J: first published as 10.1136/pgmj.40.462.179 on 1 April 1964. Downloaded from -18 POSTGRADUATE MEDICAL JOURNAL "April I964 -the form of wedge or patchy deficiencies in the curred; if contiguous, reflux was limited to the :roof and walls. These may extend for a short or lower reach of the ureter. long distance, may perhaps involve the whole Diverticula result from deficiencies in the length of the intramural ureter, and may occur bladder muscle and exhibit a particular predilec- in an intramural ureter of the congenitally short tion for the zone near which the ureters enter the type ((a) above). The effect is to render the flap bladder. valve inactive. Histological examinations of these zones reveal Furthermore, intramural segments of ortho- that ureters with orifices contiguous with diverti- topic and ectopic components of double ureters cula exhibit patchy deficiency of muscle in their may be affected in the same way. walls, whilst the engulfed ureters are almost Appearances of the Impaired Valve. The orifice totally deficient in muscle. The defect in com- of the defective ureter is then patulous, flaccid, mon between the diverticulum and the ureter is sluggish or immobile, or lies patent exhibiting ir- muscle deficiency which accounts for the vesical regular contractions. When the intramural channel bulge on the one hand and for vesico-ureteral is short, the orifice presents an appearance to the reflux on the other. cystoscopist similiar to that of a sloping tunnel The ureter with orifice adjacent but not con- entrance, and when the submucosal segment is tiguous with that of the diverticulum is com- absent, the ureteric orifice resembles the entrance petent, its muscle being adequate, though not to a rock face tunnel, vertical and sheer. always complete in its distal roofing. The The phenomenon of vesico-ureteral reflux is presence of the diverticulum however, vicariously often associated with megaureter, which is pre- elongates the intramural ureter, and thus presents sumed to be an additional malformation (Stephens, sufficient of the muscularized segment to the side- I963a). The ureteric orifice may then be cor- on position so essential to flap-valve function. respondingly enlarged and may often be readily It is concluded that the chief factor which recognized as such by cystoscopy. impairs the action of the uretero-vesical valve is

When these conditions prevail, the flocculent the lack of the muscular component of the intra-by copyright. material in the urine can be seen to undergo a mural ureter. to-and-fro movement in and out of the orifice. In addition to congenital muscular defect, This two-way flow can be confirmed by fluoro- acquired conditions such as inflammation or spinal scopy. Some ureters exhibit reflux early, others trauma may result in impaired action of the muscle. late in the period of filling of the bladder, others Pyogenic or tuberculous infection involving the again only during micturition. muscle of the ureter may inflict temporary or The two-way flow of vesico-ureteral reflux permanent damage on the uretero-vesical valve, promotes stasis, and stasis is the fore-runner of and ureteritis, as distinguished from cystitis, may

infection. initiate or exaggerate reflux. Injuries of the spine http://pmj.bmj.com/ For many patients, especially those exhibiting not uncommonly provoke reflux, and though the megaureter in association with reflux, the elimina- mechanism is not fully understood, it seems tion of stasis may be effected by the simple, regular probable that the innervation of the muscle is faithful practice of multiple micturition (Stephens rendered defective. i963b). It is indeed fortunate that such a simple trick of micturition can be invoked to prevent the (d) The Long Intramural Ureter infection which so commonly supervenes on im- The long intramural ureter lies within the pairment of valve function, an impairment which wall of the bladder and sometimes extends beyond on September 23, 2021 by guest. Protected depends upon defects of its muscle component. the confines of the bladder into the wall of the Furthermore, provided infection is eliminated urethra and vagina. All such described in this by such a method it is safe to await spontaneous lecture are ectopic members of double ureter improvement or cessation of reflux such as was systems. The anatomical course of this part of an found to occur in two-thirds of the ureters of a ectopic ureter, the changes in structure and the series of 32 patients who were observed for periods atiology of ureteroceles, are pertinent to the of five to ten years. theme of this paper. (c) Paraureteral Diverticula Course of Ectopic Ureter When a ureter lies in proximity to a vesical The ureter which issues from the caudal segment diverticulum vesico-ureteral reflux may occur. In of the kidney is called orthotopic because it opens the series of patients studied, it was possible to into the bladder in the usual situation. That make a generalisation, namely, that if the urethral which drains the cranial segment is the ectopic orifice lay within the diverticulum reflux was free. ureter. It terminates at an ectopic site, either in If the two orifices were separate, no reflux oc- the orthotopic ureter or in the trigone, urethra Postgrad Med J: first published as 10.1136/pgmj.40.462.179 on 1 April 1964. Downloaded from Alpril I964 DOL'GLAS STEPHENS: Intramural Ureter and Ureterocele I8I or genital tract. Both ureters enter the intramural contained in their intramural course a long but tunnel of the bladder together, the orthotopic normal longitudinal coat. These ureters subserved issuing into the lumen of the bladder after a short normal ureteric function in the patients studied in course beneath the vesical mucosa on to the this series. When the orifice was stenotic a lateral cornu of the trigone. The ectopic ureter ureterocele was visible at the base of the bladder. runs a submucosal course which is short when it Those ureters which issued into the urethra issues cranial or medial and close to the orthotopic beyond, were all abnormal but conformed to a orifice and long when distal to it. The ectopic pattern distinguished by the appearances of the ureter which issues into the urethra or genital orifices and the calibre of the lumens. When the tracts in its course through the submucosal plane orifice was near normal in appearance the intra- must inevitably pass within and not through the mural ureter lay invisibly beneath the trigonal sphincteric muscle coats of the urethra (Stephens, mucosa, its calibre normal or uniformly large in I963c). diameter. When the orifice was, on the one hand, Position of Orifice and Leakage. The ectopic large and patulous, or on the other hand, stenotic, ureter that issues into the bladder does not create undiscovered or absent, the ureter was generally a wetting problem, but when the orifice lies in the expanded within the walls of the trigone to form a urethra or in the vulva the circumstances are ureterocele. In some, active contractibility could different and in some instances induce uncon- be distinguished. In others, the ureterocele re- trollable leakage. mained tense, flaccid, or inert (Stephens, i963d). It is well known that ectopia of the ureter in the All the long ectopic ureters which issued into male does not cause wetting. In the female, if the the urethra were subjected to obstruction caused orifice is in the internal sphincter zone of the by the grip of the internal sphincter upon the urethra, no wetting occurs: but if it is beyond this orifice or upon the ureter itself. The way in zone, wetting may occur. which the ureteric structure reacted was variable. When the orifice lies within the internal (a) It appeared that the presence of a normal sphincter zone, it is as efficiently sealed as the ureteric orifice presaged the association of an by copyright. bladder itself and no wetting occurs. The ureter intramural ureter which exhibited a strong hyper- contains the urine between the acts of micturition, trophic muscle coat. Furthermore, histological until with relaxation of the sphincter it overflows examination revealed that it was composed not into the bladder. only of the longitudinal muscle coat but possessed When the orifice lies in the external sphincter a hypertrophic circular coat as well. In other zone or beyond, the internal sphincter no longer words, the intramural ureter resembled the acts upon the orifice but on the ureter which lies extramural ureter in structure and was equipped within its grip. Intermittent peristalsis in the to execute peristalsis. ureter or the ureteral overflow pressure or both One specimen however, revealed a normal http://pmj.bmj.com/ combined, predominate over the sphincter be- calibre amuscular ureter. Presumably it was laid tween the acts of micturition, thereby causing down in this calibre, and the absence of muscle persistent wetting. Many examples of the long accounted for the lack of hypertrophy. In submucosal ureter were shown to lack muscle, and another, thick adventitious tissue preponderated consequently power of peristalsis; the internal over the muscle components. sphincter then outmatched the defective ureter The two features which help the clinician in and prevented leakage. In special circumstances, recognising the pathology of the ureter are the however, the ureter does leak; for example when relatively normal ureteric orifice and the lack of on September 23, 2021 by guest. Protected the ureter overflows-nocturnal wetting, or when trigonal deformation. the patient stands and gravity exaggerates the (b) An abnormally large orifice, usually situated pressure in the column of urine in the ureter, the in the upper one-third of the urethra, signifies 'vertical incontinence' of Higgins, Williams and ureterocele formation in the sub-trigonal space. Nash (I95I). It has been reported that wetting Such orifices and associated ureteroceles behave first occurred in a woman after her first pregnancy. differently according to their structure. Here infection in an otherwise functionless ureter Some large orifices open widely to permit the with discharge of mucopus is a likely explanation. flow of urine, and snuggle back into the wall of the urethra as the jet ceases. The ureterocele in The Structure of the Long Intramural Ureter its distended state occupies the trigonal area and Some hint as to the structure of this ureter may obscures the view of other vesical landmarks, but be obtained from a cystoscopic study ofthe ureteral when contracted it is invisible. On occasions, a orifice and the bladder base. The long ectopic sudden contractile wave, beginning posteriorly, ureters which issued by a normal orifice in the shakes the ureterocele, converting it to a tenuous bladder were invisible beneath the trigone. They ridge under the trigone. This ridge remains Postgrad Med J: first published as 10.1136/pgmj.40.462.179 on 1 April 1964. Downloaded from I82 POSTGRADUATE MEDICAL JOURNAL April I964 visible momentarily, and then vanishes from view. origin-an aberration of expansion of the ureteric In this contracted state, the walls of the intramural bud-in this variety of ureterocele. ureter steer the ureteral catheter freely into the (c) A small or undiscovered ectopic orifice is also extramural zone. associated with ureterocele formation. The orifice Biopsy material from this type of ureterocele and adjoining ureter are subjected to double indicates that muscle, though sparse in the walls obstruction indicated by the term sphinctero- and roof, is arranged not only in longitudinal stenotic as applied to the ureterocele. The direction, but to some extent in circular or oblique orifice, being small is difficult to discover. It may distribution as well. This arrangement accounts lie in the urethra, hidden from view by the wall of for peristalsis, and active emptying of the uretero- the ureterocele, or in the ejaculatory duct, or be cele during micturition. The extreme thinness of absent. Clues as to the sites of the orifices were the muscle in the roof however, accounts for forthcoming in two patients from examination of inability to force the grip of the internal sphincter, the vas and the scrotum. A thickened vas in one the damming back of urine in the ureter, and the patient, and epididymal cysts in another indicated distension to maximum proportions of this weakly the association of malformations of both the supported trigonal part of the ureter. Wolffian ducts and the ectopic ureter, which issued Other large orifices remained limp or im- into the ejaculatory ducts. mobile; the roof wavered in the fluid stream and The behaviour of this type of ureterocele is the ureterocele remained immobile or sluggish. predictable but the structure is not: it remains The roof merely collapsed, showing minimal distended; emptying is slow because of stenosis intrinsic contractility. The ureteric catheter, in and is retarded further by the long continued this type, wound up in the capacious ureterocele grip of the sphincter. and would go no further. The walls of all -the ureteroceles which were Three unspoiled specimens obtained from post- subjected to distension were devoid of muscle mortem material confirmed the complete lack of rather than possessing excess hypertrophic muscle muscle in the roof and sides of the distal half or as would be expected. Histological studies by copyright. of more of the ureterocele. Lack of muscle explains three totally occluded ureters revealed absence of the immobility of this type of ureterocele. muscle in the distal halves or more, and patchy One patient exhibited a half-way stage between distribution in the remaining portions. This a hypertrophic tortuous ureter and a ureterocele. -distribution of muscle contrasts with that of the The tortuosites were recognisable as oval and stenotic ureterocele, the orifice of which lies within crescentic filling defects in the cystogram. The the bladder. There the muscle is hypertrophic oval filling defect was the end-on appearance of as one would expect; not thin, patchy, incomplete the ureter on the trigone and the crescents were or absent as in those of the sphinctero-stenotic tortuosities. type. http://pmj.bmj.com/ The muscular component of the ureterocele The reason for the discrepancy of muscle determines also the competence of its orifice. clothing is found in the rudimentary nature of the Reflux was demonstrable in a minority of the long deformity. The closer the orifice lies to the intramural ureters; it is likely that reflux occurs ejaculatory duct in the male or to the orifice of the when the distal part of the roof of the ureterocele is Mullerian duct in the female, the more rudi- amuscular and hence not sphincteric, or when the mentary and abnormal are the ectopic ureter and ureterocele is thick-walled, and composed chiefly its metanephric cap. Furthermore, the size of the on September 23, 2021 by guest. Protected of fibrocytes, collagen and elastic tissue, with only ectopic ureter and its transmural segment are a sprinkling of muscle. Here the reflux may dictated primarily by the developmental organizers be limited in proportion to the extent of muscular of the ureteric bud, which thus account for in- endowment of the wall. dividual variation in size from borderline to big or It is presumed that the sphincteric mechanism ballooned. Furthermore, that part of the ureter is adversely affected by lack of or impairment of which lies within the walls of the bladder may be muscle action in the walls of the ureterocele. Even subjected to the same growth stimulus which the continuation of a thick circular coat and excess excites the tube-like structure to enlarge to form fibrous tissue may impair the action of the longi- the bladder. Hence an ectopic ureter may be tudinal fibres which are the special activators ofthe stimulated to form its own bladder (ureterocele) sphincter mechanism of the ureter. within the bladder. The large orifice, often ten times normal size, Here again, the theme of intrinsic muscle en- the capacious ureterocele which may be better dowment of the ureter is again invoked to explain described as a ureterobladder, and the abnormal the behaviour ofureteroceles and some facets of the mural components all point to a developmental leakage problem. Postgrad Med J: first published as 10.1136/pgmj.40.462.179 on 1 April 1964. Downloaded from April I964 DOUGLAS STEPHENS: Intramural Ureter and Ureterocele I83 Prolapse of Ureterocele Histological studies of the orthotopic orifice Prolapse of the ureterocele may occur from the and adjacent ureter have shown that here again, bladder into the urethra and cause obstruction for the muscle is deficient in many instances, with the duration of the prolapse. It involves only twofold effect. First reflux from the bladder those instances in which the ureteric orifices lie in occurs and secondly the terminal ureter being the urethra. It seems that factors conducive to adynamic adversely affects the propulsion of urine maintaining distension of the ureterocele during into the bladder, thus aggravating obstruction. voiding, together with the intrinsic encroachment In these ways, any or all orifices may be im- of the ectopic ureter into the urethra are essential paired causing deterioration in kidney function to prolapse. The factors are, firstly, refilling from with concomitant depression in hetalth. below during voiding-urethro-ureteral reflux- an event ensuing on absence of muscle in the Summary ureter; secondly, retention of urine induced by stenosis; and thirdly, rapid overfilling from above The uretero-vesical valve which governs one- by active peristalsis of a large full ureter during way flow of urine is intrinsic in that part of the the act of micturition. ureter which lies in the submucous plane of the In the female, the prolapsed ureterocele appears intramural course through the bladder wall. It at the external urethral orifice and receives im- relies for its action on its side-on position relative mediate treatment, but in the male prolapse or to the lumen of the bladder and on its longitudinal partial prolapse is occult and sinister and may be muscle cothponent, which activates its flap valve. identified only by a filling defect in the posterior Defects of this submucosal section of the ureter urethra on micturition cysto-urethrography. Re- either of length, of muscle or both lead to a two- duction of the prolapse relieves the obstruction, way flow, stasis and infection. The simple and though recurrence is likely. Insidious renal im- faithful practice of multiple micturition by the pairment ensues in the undiagnosed and untreated patient, instructed by an informed paediatrician occult type. and supervised by the parent effectively overcomes stasis in the megaureter and eliminates infection. by copyright. Obstruction of the Ipsilateral Orthotopic When the submucosal segment is abnormally Ureter and Contralateral Ureter long, the muscle component may be defective The orifices of both these ureters are liable to rendering the valve incompetent. When this obstruction by the distended ectopic ureterocele. segment is of sufficient length to extend into the The ipsilateral orthotopic ureter is trapped and urethra ureterocele formation is not uncommon; squeezed flat between the distended ectopic ureter defects in its muscle coat which impair emptying, and the mucous membrane of the trigone. The permit refilling during voiding and promote fuller the ureterocele and adjoining ureter, the prolapse of the ureterocele. If the ureter issues http://pmj.bmj.com/ greater the squeeze. into the urethra beyond the internal sphincter The opposite ureter may be drawn up onto the Zone, wetting ensues, but even this is capricious slopes of the ureterocele and its orifice and ad- by nature of the varying degree of the muscle joining ureter pressed flat. endowment of its walls.

REFERENCES HIGGINS, T. T., WILLIAMS, D. I., and NASH, D. F. E. (195I): 'The Urology of Childhood', p. 2. London: Butterworth. on September 23, 2021 by guest. Protected HUTCH, J. A. (I962): The Role of the Ureterovesical Junction in the Natural History of Pyelonephritis, J. Urol. (Baltimore), 88, 354. STEPHENS, F. D., and LENAGHAN, D. (I962): The Anatomical Basis and Dynamics of Vesicoureteral 87, 669. Reflux, Ibid., (I963a): 'Congenital Malformations of the Rectum, Anus and Genito-Urinary Tracts', p. 123. Edinburgh: E. & S. Livingstone. (I963b): Ibid., p. 125 and 145. (I963c): Ibid., p. 157. (I963d): Ibid., p. 178.