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Embryology of urinary incontinence
EMBRYOLOGYOFURINARYINCONTINENCE DAVID H. ZORNOW,
M.D.
From the Danville Urologic Clinic, Danville, Virginia
ABSTRACT - Congenital incontinence may be divided into primary and secondary types. Primary incontinence refers to the development of a conduit which bypasses the normal sphincter mechanism, while secondary incontinence develops after a congenital outlet obstruction leads to bladder decompensation and overflow. The embyogenesis of the various forms of primary incontinence is described in detail and management is discussed. -
Congenital abnormality of the urinary tract must always be considered in the evaluation of urinary incontinence. The etiology of congenital incontinence may test the diagnostic acumen of the most astute clinician when an extravesical ectopic ureter is present, or may be grossly evident on physical examination as in exstrophy of the bladder. Congenital urinary incontinence can be divided into the primary and secondary types. Primary incontinence occurs when through a developmental error a conduit is established without a sphincteric mechanism between the lower urinary tract and the outside. Secondary incontinence is manifested by a developmental anomaly which causes obstruction, leading to decompensation of the bladder, and eventual inability of the sphincteric mechanism to control overflow. It is the purpose of this report to discuss the embryogenesis and management of the various types of primary incontinence. Congenital Causes of Primary Incontinence Patent urachus In the newborn two extra embryonic structures exist which must be severed at birth and by obliteration of their lumens become nonfunctional. The first is the communication of the midgut with the yolk sac and is of no concern to this discussion. The second is the connection of the allantoic stalk to the anterior cloaca, and it is by the failure of this structure to close that a patent urachus persists causing incontinence at the umbilicus.
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The urachus develops from the anterior cloaca and is approximately 3 to 5 cm. in length in the adult. A portion of the urachus runs in the dome of the bladder before becoming a fibrous band, which terminates in the abdominal wall between the transversalis fascia and the peritoneum. Embryogenesis Incontinence at the umbilicus can be divided into the congenital and the acquired types (Fig. 1). The developmental mechanisms of the congenital type are two in number; the first and simplest to understand is the true patent urachus. As the bladder forms from the anterior cloaca, its intraembryonic connection with the allantois persists leaving a patent tube between the bladder and the umbilicus. In the second form, the urachus fails to develop, and the anterior cloaca is in direct communication with the umbilicus. The ventral bladder in this form of the anomaly lies at the level of the umbilicus because of the failure of bladder descent. Because of the direct communication between the bladder and the umbilicus, this variant should probably be considered a true vesicoumbilical fistula rather than a patent urachus. The acquired form of this disorder is always secondary to some form of vesical outlet obstruction and occurs in adults with no prior history of umbilical fistula. As noted by Begg in 1927, l “when the formation and descent of the urachus follow the normal lines, it can never at any future period act as a conduit to convey urine from the bladder to the umbilicus.” Although several cases of acquired umbilical
293
Congenital
Acquired
Urinary
rxtraviwtion
Tranrversa fascia
Bladder perforation
Uretheral
FIGURE 1. incontinence at umbilicus: (a) True patent urachus; after perforation of bladd er ( a and b from Gray and Skandalakis,
fistula have been reported, the mechanism is completely different from that previously described. Outlet obstruction occurs, which leads to a perforation of the bladder and extravasation into the prevesical space. From the point of perforation, the urine travels along the anterior abdominal wall between the transversalis fascia and the peritoneum and exits at the umbilicus. Patent urachus is an extremely rare anomaly. Nix et ~1.’ found 3 cases in 200,000 hospital admissions in Boston and 3 cases in 1,168,760 admissions in New Orleans. McCauley and Lichtenheld3 noted 2 cases in 108,000 admissions. The incidence of patent urachus in males was noted to be twice as prevalent as in females. Leakage of urine at the umSymptoms. bilicus is the obvious symptom of this form of incontinence. The development of an enlarging or tender mass in the anterior abdominal wall may indicate the development of a urachal cyst secondary to closure of the fistula at the umbilicus, at the bladder level, or both. Treatment. The treatment of this type of incontinence depends on the etiology. In the congenital form the excision of the umbilicus and the patent tract including the involved dome of the bladder is the proper approach. In the acquired form, proper and adequate drainage must be achieved followed by relief of the underlying obstruction. Ectopic
ureters
The extravesical ectopic ureter anomaly that may lead to multiple
294
is a rare social and
obstructlon
jb) vesicoumbilical jstula; (c) extravasation 1972,16 as redrawn from Cullen, 191617).
psychologic problems if allowed to persist. It frequently goes unrecognized before the child is toilet trained and may mistakenly be treated as psychologically induced enuresis for many years. Crenshaw4 found 1 case in 81,150 patients at the Mayo Clinic while Mills5 found 112 ectopic orifices in 850 cases with ureteral duplication. The incidence of this anomaly is three to four times as frequent in females as compared with males. Some of the disparity seen between the sexes is undoubtedly due to the more difficult diagnosis in the male. Since all ectopic ureteral orifices in the male lie proximal to the external sphincter, incontinence does not occur. In the female the ectopic orifice may be found in the posterior wall of the urethra, the vestibule, vagina, cervix, uterine cavity, or Gartner’s duct, and all may demonstrate the symptom of incontinence. Embryogenesis. As the mesonephric ducts develop, they take a sharp bend at the level of the twenty-eighth somite just before joining the cloaca. It is at this point that the normal ureteral buds appear and start their ascent toward the metanephrogenic tissue. By a series of repeated subdivisions some twelve generations of the tubules are formed into the renal pelvis, major and minor calyces, and the collecting tubules.6 At the caudal end of the ureteric buds the changes are more complex. As the urorectal septum divides the cloaca, the bladder emerges as a separate entity and receives the common stems of the mesonephric ducts and the ureteric buds. By a complex series of growth processes, the ureters are incorporated into the bladder
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wall and assume a lateral position while the mesonephric ducts form the trigone of the bladder and come to lie with their openings close together at Miiller’s tubercle. It is this short segment from the bladder neck to Miiller’s tubercle (the future seminal colliculus in the male) that is analogous to the entire urethra in the female. The early division of the ureteric bud or the differentiation of separate ureteric buds followed by their incorporation into the bladder wall will lead to the presence of multiple ureteric orifices within the bladder. Extravesical ectopic ureters arise from the development of ureteric buds above the level of the twenty-eighth somite. Because of their more cranial position, these ureters fail to be incorporated into the bladder wall which can then lead to an insertion into the urethra at any point proximal to Miiller’s tubercle in the male or the vestibule in the female (Fig. 2). A still higher origin of the ureteric bud from the mesonephric duct results in complete failure of the ureter to be incorporated into the bladder or urethra, and it remains confluent with the mesonephric duct in the male and its vestiges in the female. In the male the result is a ureter that may open into the ductus deferens or seminal vesicle (Fig. 3). These ectopic orifices in the male never
FEMALE
- Rectvm (rare)
Vagina’ 25%
Sites of ectopic ureter-al or-i&es und their relative frequencies of occurrence in men and women (from Gray and Skandalakis, 197216). FIGURE
2.
Hind-Gut Mesonephric or Wolffian Duct Allantois -Kidney Ureter
b
d Embryogenesis of extravesical ectopic ureter in male: (a, h, and c) Normal development showing observing ureteral bud mesonephric duct (black) being absorbed into bladder wall; (d) a b normal development originating above level of twenty-eighth somite leading to failure of absorbtion into bladder wall and ectopia into ductus deferens or seminal cesical (from Seitzman and Patton, 196Ol’). FIGURE
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,
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FIGURE 4. Embryogenesis of epispadias and bladder exstrophy. (A) Nornd relationships of developing penis in embryo of eighth week. Note that urethral groove (asterisk) is directly in line with urogenital or$ce. In schematic cross section of genital tubercle, developing corpus cavernosum and corpus spongiosum flanking urethral groove are indicated by heavier stippling. (B) Hypothetical stage in genesis of exstrophy of bladder and epispadias. Compare with A. Note that belly wall in midline (asterisk) is composed of thinning plate of ectoderm and endoderm unreinforced by mesoderm (from Patten and Barry, 1 95214).
In the male incontinence is Symptoms. rarely the presenting symptom although the presence of urine in the prostatic urethra may lead to frequency of micturition with the passage of only small amounts of urine or enuresis. Symptoms of genitourinary tract infection, however, most commonly herald an extravesical ectopic ureter in the male. Rectal examination may reveal a distended cystic seminal vesicle in cases in which the ureter empties into this structure. In the female the classic presenting symptom is continuous incontinence associated with a sensation of bladder distention and normal micturition at periodic intervals. Treatment. After complete evaluation of the upper urinary tract, treatment must be tailored to the individual case. If the kidney drained by the ectopic ureter appears normal, ureteroneocystotomy would be the procedure of choice. Should the upper segment be badly damaged or nonfunctioning, heminephrectomy is usually performed. When a destroyed collecting system is associated with a nonduplicated ectopic ureteral orifice, nephrectomy is indicated. In both the duplicated and nonduplicated conditions removal of the entire ectopic ureter is desirable since it may serve as a source of persistent infection. Defects
of Infraumbilical
Body Wall
No discussion of embryogenic incontinence would be complete without reference to the spectrum of congenital anomalies that arise from the maldevelopment of the infraumbilical body wall. Epispadias, bladder exstrophy, and duplication of the urethra can be traced to the failure of fusion of the muscles of the ventral abdominal wall. Bladder
exstrophy
lead to incontinence since in each case the orifice is proximal to the external urinary sphincter. In the female the distal mesonephric duct becomes vestigial forming the duct of the epoophoron or Gartner’s duct. Since Gartner’s duct runs into the wall of the cervix and vagina, it is postulated that ectopic orifices may occur by the rupture of this “mesoureteric duct” into the cervical and vaginal lumens. Since the female has no structure analogous to the external urinary sphincter in the male, these patients all present with incontinence of some degree.
Exstrophy of the bladder may be of two types, incomplete and complete. In the incomplete form the opening is suprapubic in position, the pubic bones united, and no epispadias is present. The complete form is always associated with complete epispadias, wide separation of the pubic bones, and exposure of the posterior bladder wall. The incidence of bladder exstrophy has been estimated at one in 40 to 50,000 births with a three to one male to female ratio.7 Exstrophy of the cloaca is usually a fatal condition and will not be dealt with in this discussion
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Emhryogenesis. The cloaca of six somite embryos is simply a blind caudal expansion of the hindgut which is in direct contact with the ectoderm. The point at which the ectoderm and endoderm are in contact constitutes the cloaca1 membrane which extends from the tail bud to the body stalk. By the seventh week a mesenchymal mass, the urorectal septum, has divided the cloaca into a ventral bladder and a dorsal rectum, and the cloaca1 membrane into a urogenital membrane and an anal membrane. The subsequent rupture of the urogenital membrane creates the urogenital sinus which can be divided into a pelvic portion near the bladder and a phallic portion which extends to the genital tubercle distally. The disintegration of the urogenital membrane converts the phallic portion of the urogenital sinus into an open groove which is related to the underside of the base of the phallus (Fig. 4A). It is at this stage of the normal development of the urinary tract that defective development of the ventral infraumbilical body wall can occur (Fig. 5). Wyburn’ suggested that exstrophy of the bladder was due to the failure of “secondary” mesoderm to develop from the primitive streak. He believed that this mesoderm swept around the margins of the caudal end of the cloaca1 membrane and invaded the space between the ectodermal and endodermal layers of the membrane. If this normal process should fail to occur, the continued contact of two primary layers of the cloaca1 membrane would create an unstable condition leading inevitably to the rupture of the membrane. Paul and Kanagasuntherang suggested that the persistence of the cloaca1 membrane was not due to failure of the secondary mesoderm to form but rather to the failure of the advancing edges of the mesoderm to fuse in the midline, again leaving the ectodermal and endodermal layers of the cloaca1 membrane in apposition. To support their point of view, Paul and Kanagasuntherang noted the completeness of the development of the body wall up to the medial borders of the rectus sheath in all cases they studied. attempted to reconcile these opGlenister” posing points of view, as shown in Figure 6, by noting that there are two types of mesoderm, both of which are derived from the primitive streak. The primitive streak gives rise to the paraxial intraembryonic mesoderm which is present between ectoderm and endoderm. In the somite embryo the paraxial mesoderm be-
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h FIGURE 5. Schematic diagrams contrasting normul with hypothetical abnormal positional changes of primordia of genital tubercle with relation to cloaca1 membrane and urogenital orijice: (a, c, and e) represent normal stages; (b, d, and f),stages in genesis of eutrophy and epispadias (from Patten and Barry, 195214).
comes subdivided into a medially placed segmented component, the somites, and an unsegmented lateral plate of mesoderm. The lateral plate mesoderm is divided by the developing celom and gives rise to a visceral layer which forms the muscular and serous coats of the gut and its derivatives, and a parietal layer which contributes to the body wall. Since the celomic cavity does not extend into the most caudal portion of the embryo, the lateral plate mesoderm is not divided at this point. This represents Wyburn’s “secondary” layer mesoderm as it extends around the sides of the cloaca1 membrane splitting the ectoderm and endoderm. The deep part of this mesoderm contributes to the bladder musculature and the superficial part tc the infraumbilical body wall. If these lateral plates of mesoderm fail to fuse in the midline, the cloaca1 membrane will persist and eventually rupture creating an opening between the outside of the embryo and the cloaca or later the urogenital sinus (Fig. 4B). Glenister further maintains that the mesodermal layer
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4.- *9 3-_
- -10 --II
2-’
2
FIGURE 6. Diagram illustrating disposition of mesoderm at caudal end of somite embryo. Observer is looking down into inside of caudal end of embryo. (1) Surface epithelium; (2) somatic layer of lateral plate mesoderm; (3) celomic cavity; (4) viseral layer of lateral plate mesoderm; (5) intermediate cell mass or nephrogenic cord; (6) somite; (7) neural tube; (8) notochord; (9) unsegmented paraxial mesoderm; (10) primitive streak; (11) site of developing urorectal septum; (12) site of definitive cloaca1 membrane; and (13) infraumbilical abdominal wall and site where mesois deficient in derm exstrophy of bladder (from Glenister, 1958lO).
Muecke12 reported similar results in 3 of 20 patients in their series. In view of these rather discouraging results, most authors now advocate urinary diversion and cystectomy as the treatment of choice. most encouraging results in Spence13 reported 31 patients treated by ureterosigmoidostomy with follow-up of five years in 22 and ten years or more in 16 of the patients.
that created a normal appearing abdominal wall in the cases studied by Paul and Kanagasuntheran was derived not from the unsegmented lateral mesoderm but from the somites of the lower thoracic region. In summary then, Wyburn’s “secondary” mesoderm fails to fuse in the midline leading eventually to rupture of the cloaca1 membrane. The somatic musculature of Paul and Kanagasuntheran can develop normally only as far as the margin of the cleft produced in the exstrophic bladder, therefore accounting for the normal development of the abdominal wall up to the medial border of the rectus sheath. Symptoms. Symptoms secondary to the anterior abdominal exteriorization of the bladder include saturation of the overlying clothing and excoriation of the skin surrounding the exposed bladder. Bleeding and edema of the exposed bladder mucosa is common, and this continuous irritation may lead to glandular cystitis and occasionally adenocarcinoma. Treatment. The results of primary closure of the bladder and urethra have been most discouraging. Lattimer and Smith” reported on 70 patients, 43 of whom were males. Only 3 patients in this series were continent of urine over two hours during the day. Marshall and
Just as exstrophy can occur without epispadias so too can epispadias occur without exstrophy. The association of incontinence with epispadias occurs only in the most severe form, the complete epispadias in which the entire dorsum of the urethra is open with the groove so formed involving the internal sphincter (Fig. 7). Epispadias has been estimated to occur once in 30,000 deliveries with males predominating three to one. Embryogenesis. As the “secondary” mesoderm of Wyburn develops, it extends around the margin of the caudal part of the infraumbilical membrane and gives rise to the paired phallic tubercles. Patten and BarryI suggested that as the phallic tubercles develop, they take up an
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FIGURE 7. i'ato c) First, second, and third-degree forms of epispadias in male. jd and e) Second and thirddegree forms of epispadias in female. First-degree epispadias is represented by bi$d clitoris. Only third-degree forms of epispadias which inooloe internal sphincter lead to incontinence in male and female (from Welch, K. I.,‘” used with permission).
abnormally caudal position with reference to the proctoderm (Fig. 5). When this occurs, the urorectal fold comes into direct contact with the genital tubercle. The urogenital sinus is thus positioned on the dorsal surface of the developing phallus rather than in its normal ventral location giving rise to an epispadic urethral groove (Fig. 4). S ymptoins. Complete epispadias gives rise to incontinence in both males and females. Because of the obvious epispadiac groove in the male, the diagnosis should seldom be missed. In the female the physical findings are less obvious and may lead to social ostracism and prolonged treatment for psychologic incontinence if allowed to go unrecognized. Surgical intervention should be Treatment. postponed until the child is about three years of age. A review of the literature indicates that continence can be restored in about 80 per cent of all cases of epispadias.15 In the remaining 10 per cent a urinary diversion may be necessary
FIGURE 8. Duplications of posterior urethra arising independently from bladder. (a to d) Complete separation of urethras. (e and ”f) Separate urethras , becoming confluent distally; (f) will not result in urethra joins normal incontinence since accessory (from Gray urethra proximal to external sphincter and Skandalakis16).
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a
b
L C
t
d
t e
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because of deteriorating tinued incontinence.
renal function or con-
Duplication of urethra Duplication of the urethra represents the mildest anomaly of the infraumbilical body wall. Approximately 100 cases of urethral duplication have been reported in the literature. Although there are several variant forms of urethral duplications, those causing incontinence can be divided into two types (Fig. 8). First, complete duplication is represented anatomically by two completely separate urethras which extend from the bladder to the outside. One is the normal urethra, and the second is an accessory urethra which may open at any point along the phallus. Since the accessory channel may have no sphincter mechanism, some patients are incontinent of urine. Second, incomplete duplication anatomically is represented by an accessory urethra that originates in the bladder and empties distally into the normal urethra. If the opening is proximal to the external sphincter, the patient will remain continent. An opening distal to the external sphincter, however, will result in incontinence. Embryogenesis. As discussed in epispadias, the lateral anlage of the paired genital tubercles normally form a bridge across the ventral end of the cloaca1 membrane. When the tubercles unite in a posterior position in relation to the urorectal fold, the scene is set for the entire spectrum of congenital anomalies to develop, from exstrophy to incomplete duplication. Urethral duplication develops when the posterior displacement of the genital tubercles is less severe in position than that seen in epispadias and exstrophy. Accessory urethral channels that Symptoms. do not arise from the bladder may cause no symptoms whatsoever. Should the accessory channel originate in the bladder, however, total incontinence may be the presenting symptom associated with uremic excoriations of the skin.
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Total extirpation of the accessory Treatment. urethral channel is indicated in cases in which incontinence is manifested. Dorsal chordee often accompanies this lesion and should be corrected at the time of surgery. 1040 Main Street Danville, Virginia 24541 ACKNOWLEDGMENT. To Dr. M. W. Woodruff, Chairman, Division of Urology, Albany Medical College, for his support in the preparation of this article.
References 1. Begg RC: The urachus and umbilical fistulae, Surg. Gynecol. Obstet. 45: 165 (1927). 2. Nix JT, Menville JG, Albert M, and Wendt DL: Congenital patent urachus, J. Urol. 79: 264 (1958). 3. McCauley RT, and Lichtenheld FR: Congenital patent urachus, South. Med. J. 53: 1138 (1969). 4. Crenshaw JL: Ureter with extravesical orifice: supernumery ureter ending blindly; crossed ureteral ectopia; stones in extrapelvie cystocele; report of 11 cases, J. Ural. 43: 82 (1940). 5. Mills JC: Complete unilateral duplication of ureter with analysis of the literature, Ural. Cutan. Rev. 43: 444 (1939). 6. Arev LB: Develoumental Anatomv. 6th ed.. Philadelnhia. W. B. Saunders Co., 1954, p. 299. ” A 7. Campbell MF, and Harrison JH: Urology, 3rd ed., Philadelphia, W. B. Saunders Co., 1970, p. 1558. 8. Wybum GM: The development of the intra-umbilical portion of the abdominal wall with remarks on the etiology of ectopic vesicae, J. Anat. 71: 201 (1937). 9. Paul M, and Kanagasuntheran R: The congenital anomalies of the lower urinarv tract, Br. 1. Ural. 28: 64. 118 (1956). 10. Glenister TW: A correlation of the normal and ‘abnormal development of the penile urethra and of the intra-umbilical abdominal wall, ibid. 39: 117 (1958). 11. Lattimer JK, and Smith MJV: Exstrophy closure; a followup in seventy cases, J. Urol. 85: 356 (1965). 12. Marshall VF, and Muecke EC: Variations in exstrophy of the bladder, ibid. 88: 766 (1962). 13. Spence, HM: Ureterosigmoidostomy for exstrophy of bladder: results in personal series of thirty-one cases, Br. I. Ural. 38: 36 (1966). 14. Patten BM, and Barry A: The genesis of exstrophy of the bladder and eoisoadias. Am. 1. Anat. 99: 35 (1952). 15. Welch -Kjz Epispadias, in Mustard, ‘W. T., et al. Eds.: Pediatric Surgery, 2nd ed., Chicago, Year Book Medical Publishers, 1969, vol. 2, p, 1337. 16. Gray SW, and Skandalakis JE: Embryology for Surgeons, Philadelphia, W. B. Saunders Co., 1972, p. 527. 17. Cullen TS: Embryology-Anatomy and Diseases of the Umbilicus Together with Diseases of the Urachus. Philadelohia. I , W. B. Saunders Co., 1916, p. 488. 18. Seitzman DM, and Patten JF: Ureteral ectopia: combined ureteral and vas deferens anomaly, J. Urol. 84: 694 (1969).
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OCTOBER
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VOLUME X, NUMBER 4
M.D.
From the Danville Urologic Clinic, Danville, Virginia
ABSTRACT - Congenital incontinence may be divided into primary and secondary types. Primary incontinence refers to the development of a conduit which bypasses the normal sphincter mechanism, while secondary incontinence develops after a congenital outlet obstruction leads to bladder decompensation and overflow. The embyogenesis of the various forms of primary incontinence is described in detail and management is discussed. -
Congenital abnormality of the urinary tract must always be considered in the evaluation of urinary incontinence. The etiology of congenital incontinence may test the diagnostic acumen of the most astute clinician when an extravesical ectopic ureter is present, or may be grossly evident on physical examination as in exstrophy of the bladder. Congenital urinary incontinence can be divided into the primary and secondary types. Primary incontinence occurs when through a developmental error a conduit is established without a sphincteric mechanism between the lower urinary tract and the outside. Secondary incontinence is manifested by a developmental anomaly which causes obstruction, leading to decompensation of the bladder, and eventual inability of the sphincteric mechanism to control overflow. It is the purpose of this report to discuss the embryogenesis and management of the various types of primary incontinence. Congenital Causes of Primary Incontinence Patent urachus In the newborn two extra embryonic structures exist which must be severed at birth and by obliteration of their lumens become nonfunctional. The first is the communication of the midgut with the yolk sac and is of no concern to this discussion. The second is the connection of the allantoic stalk to the anterior cloaca, and it is by the failure of this structure to close that a patent urachus persists causing incontinence at the umbilicus.
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/ OCTOBER
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/ VOLUME
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The urachus develops from the anterior cloaca and is approximately 3 to 5 cm. in length in the adult. A portion of the urachus runs in the dome of the bladder before becoming a fibrous band, which terminates in the abdominal wall between the transversalis fascia and the peritoneum. Embryogenesis Incontinence at the umbilicus can be divided into the congenital and the acquired types (Fig. 1). The developmental mechanisms of the congenital type are two in number; the first and simplest to understand is the true patent urachus. As the bladder forms from the anterior cloaca, its intraembryonic connection with the allantois persists leaving a patent tube between the bladder and the umbilicus. In the second form, the urachus fails to develop, and the anterior cloaca is in direct communication with the umbilicus. The ventral bladder in this form of the anomaly lies at the level of the umbilicus because of the failure of bladder descent. Because of the direct communication between the bladder and the umbilicus, this variant should probably be considered a true vesicoumbilical fistula rather than a patent urachus. The acquired form of this disorder is always secondary to some form of vesical outlet obstruction and occurs in adults with no prior history of umbilical fistula. As noted by Begg in 1927, l “when the formation and descent of the urachus follow the normal lines, it can never at any future period act as a conduit to convey urine from the bladder to the umbilicus.” Although several cases of acquired umbilical
293
Congenital
Acquired
Urinary
rxtraviwtion
Tranrversa fascia
Bladder perforation
Uretheral
FIGURE 1. incontinence at umbilicus: (a) True patent urachus; after perforation of bladd er ( a and b from Gray and Skandalakis,
fistula have been reported, the mechanism is completely different from that previously described. Outlet obstruction occurs, which leads to a perforation of the bladder and extravasation into the prevesical space. From the point of perforation, the urine travels along the anterior abdominal wall between the transversalis fascia and the peritoneum and exits at the umbilicus. Patent urachus is an extremely rare anomaly. Nix et ~1.’ found 3 cases in 200,000 hospital admissions in Boston and 3 cases in 1,168,760 admissions in New Orleans. McCauley and Lichtenheld3 noted 2 cases in 108,000 admissions. The incidence of patent urachus in males was noted to be twice as prevalent as in females. Leakage of urine at the umSymptoms. bilicus is the obvious symptom of this form of incontinence. The development of an enlarging or tender mass in the anterior abdominal wall may indicate the development of a urachal cyst secondary to closure of the fistula at the umbilicus, at the bladder level, or both. Treatment. The treatment of this type of incontinence depends on the etiology. In the congenital form the excision of the umbilicus and the patent tract including the involved dome of the bladder is the proper approach. In the acquired form, proper and adequate drainage must be achieved followed by relief of the underlying obstruction. Ectopic
ureters
The extravesical ectopic ureter anomaly that may lead to multiple
294
is a rare social and
obstructlon
jb) vesicoumbilical jstula; (c) extravasation 1972,16 as redrawn from Cullen, 191617).
psychologic problems if allowed to persist. It frequently goes unrecognized before the child is toilet trained and may mistakenly be treated as psychologically induced enuresis for many years. Crenshaw4 found 1 case in 81,150 patients at the Mayo Clinic while Mills5 found 112 ectopic orifices in 850 cases with ureteral duplication. The incidence of this anomaly is three to four times as frequent in females as compared with males. Some of the disparity seen between the sexes is undoubtedly due to the more difficult diagnosis in the male. Since all ectopic ureteral orifices in the male lie proximal to the external sphincter, incontinence does not occur. In the female the ectopic orifice may be found in the posterior wall of the urethra, the vestibule, vagina, cervix, uterine cavity, or Gartner’s duct, and all may demonstrate the symptom of incontinence. Embryogenesis. As the mesonephric ducts develop, they take a sharp bend at the level of the twenty-eighth somite just before joining the cloaca. It is at this point that the normal ureteral buds appear and start their ascent toward the metanephrogenic tissue. By a series of repeated subdivisions some twelve generations of the tubules are formed into the renal pelvis, major and minor calyces, and the collecting tubules.6 At the caudal end of the ureteric buds the changes are more complex. As the urorectal septum divides the cloaca, the bladder emerges as a separate entity and receives the common stems of the mesonephric ducts and the ureteric buds. By a complex series of growth processes, the ureters are incorporated into the bladder
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wall and assume a lateral position while the mesonephric ducts form the trigone of the bladder and come to lie with their openings close together at Miiller’s tubercle. It is this short segment from the bladder neck to Miiller’s tubercle (the future seminal colliculus in the male) that is analogous to the entire urethra in the female. The early division of the ureteric bud or the differentiation of separate ureteric buds followed by their incorporation into the bladder wall will lead to the presence of multiple ureteric orifices within the bladder. Extravesical ectopic ureters arise from the development of ureteric buds above the level of the twenty-eighth somite. Because of their more cranial position, these ureters fail to be incorporated into the bladder wall which can then lead to an insertion into the urethra at any point proximal to Miiller’s tubercle in the male or the vestibule in the female (Fig. 2). A still higher origin of the ureteric bud from the mesonephric duct results in complete failure of the ureter to be incorporated into the bladder or urethra, and it remains confluent with the mesonephric duct in the male and its vestiges in the female. In the male the result is a ureter that may open into the ductus deferens or seminal vesicle (Fig. 3). These ectopic orifices in the male never
FEMALE
- Rectvm (rare)
Vagina’ 25%
Sites of ectopic ureter-al or-i&es und their relative frequencies of occurrence in men and women (from Gray and Skandalakis, 197216). FIGURE
2.
Hind-Gut Mesonephric or Wolffian Duct Allantois -Kidney Ureter
b
d Embryogenesis of extravesical ectopic ureter in male: (a, h, and c) Normal development showing observing ureteral bud mesonephric duct (black) being absorbed into bladder wall; (d) a b normal development originating above level of twenty-eighth somite leading to failure of absorbtion into bladder wall and ectopia into ductus deferens or seminal cesical (from Seitzman and Patton, 196Ol’). FIGURE
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FIGURE 4. Embryogenesis of epispadias and bladder exstrophy. (A) Nornd relationships of developing penis in embryo of eighth week. Note that urethral groove (asterisk) is directly in line with urogenital or$ce. In schematic cross section of genital tubercle, developing corpus cavernosum and corpus spongiosum flanking urethral groove are indicated by heavier stippling. (B) Hypothetical stage in genesis of exstrophy of bladder and epispadias. Compare with A. Note that belly wall in midline (asterisk) is composed of thinning plate of ectoderm and endoderm unreinforced by mesoderm (from Patten and Barry, 1 95214).
In the male incontinence is Symptoms. rarely the presenting symptom although the presence of urine in the prostatic urethra may lead to frequency of micturition with the passage of only small amounts of urine or enuresis. Symptoms of genitourinary tract infection, however, most commonly herald an extravesical ectopic ureter in the male. Rectal examination may reveal a distended cystic seminal vesicle in cases in which the ureter empties into this structure. In the female the classic presenting symptom is continuous incontinence associated with a sensation of bladder distention and normal micturition at periodic intervals. Treatment. After complete evaluation of the upper urinary tract, treatment must be tailored to the individual case. If the kidney drained by the ectopic ureter appears normal, ureteroneocystotomy would be the procedure of choice. Should the upper segment be badly damaged or nonfunctioning, heminephrectomy is usually performed. When a destroyed collecting system is associated with a nonduplicated ectopic ureteral orifice, nephrectomy is indicated. In both the duplicated and nonduplicated conditions removal of the entire ectopic ureter is desirable since it may serve as a source of persistent infection. Defects
of Infraumbilical
Body Wall
No discussion of embryogenic incontinence would be complete without reference to the spectrum of congenital anomalies that arise from the maldevelopment of the infraumbilical body wall. Epispadias, bladder exstrophy, and duplication of the urethra can be traced to the failure of fusion of the muscles of the ventral abdominal wall. Bladder
exstrophy
lead to incontinence since in each case the orifice is proximal to the external urinary sphincter. In the female the distal mesonephric duct becomes vestigial forming the duct of the epoophoron or Gartner’s duct. Since Gartner’s duct runs into the wall of the cervix and vagina, it is postulated that ectopic orifices may occur by the rupture of this “mesoureteric duct” into the cervical and vaginal lumens. Since the female has no structure analogous to the external urinary sphincter in the male, these patients all present with incontinence of some degree.
Exstrophy of the bladder may be of two types, incomplete and complete. In the incomplete form the opening is suprapubic in position, the pubic bones united, and no epispadias is present. The complete form is always associated with complete epispadias, wide separation of the pubic bones, and exposure of the posterior bladder wall. The incidence of bladder exstrophy has been estimated at one in 40 to 50,000 births with a three to one male to female ratio.7 Exstrophy of the cloaca is usually a fatal condition and will not be dealt with in this discussion
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Emhryogenesis. The cloaca of six somite embryos is simply a blind caudal expansion of the hindgut which is in direct contact with the ectoderm. The point at which the ectoderm and endoderm are in contact constitutes the cloaca1 membrane which extends from the tail bud to the body stalk. By the seventh week a mesenchymal mass, the urorectal septum, has divided the cloaca into a ventral bladder and a dorsal rectum, and the cloaca1 membrane into a urogenital membrane and an anal membrane. The subsequent rupture of the urogenital membrane creates the urogenital sinus which can be divided into a pelvic portion near the bladder and a phallic portion which extends to the genital tubercle distally. The disintegration of the urogenital membrane converts the phallic portion of the urogenital sinus into an open groove which is related to the underside of the base of the phallus (Fig. 4A). It is at this stage of the normal development of the urinary tract that defective development of the ventral infraumbilical body wall can occur (Fig. 5). Wyburn’ suggested that exstrophy of the bladder was due to the failure of “secondary” mesoderm to develop from the primitive streak. He believed that this mesoderm swept around the margins of the caudal end of the cloaca1 membrane and invaded the space between the ectodermal and endodermal layers of the membrane. If this normal process should fail to occur, the continued contact of two primary layers of the cloaca1 membrane would create an unstable condition leading inevitably to the rupture of the membrane. Paul and Kanagasuntherang suggested that the persistence of the cloaca1 membrane was not due to failure of the secondary mesoderm to form but rather to the failure of the advancing edges of the mesoderm to fuse in the midline, again leaving the ectodermal and endodermal layers of the cloaca1 membrane in apposition. To support their point of view, Paul and Kanagasuntherang noted the completeness of the development of the body wall up to the medial borders of the rectus sheath in all cases they studied. attempted to reconcile these opGlenister” posing points of view, as shown in Figure 6, by noting that there are two types of mesoderm, both of which are derived from the primitive streak. The primitive streak gives rise to the paraxial intraembryonic mesoderm which is present between ectoderm and endoderm. In the somite embryo the paraxial mesoderm be-
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h FIGURE 5. Schematic diagrams contrasting normul with hypothetical abnormal positional changes of primordia of genital tubercle with relation to cloaca1 membrane and urogenital orijice: (a, c, and e) represent normal stages; (b, d, and f),stages in genesis of eutrophy and epispadias (from Patten and Barry, 195214).
comes subdivided into a medially placed segmented component, the somites, and an unsegmented lateral plate of mesoderm. The lateral plate mesoderm is divided by the developing celom and gives rise to a visceral layer which forms the muscular and serous coats of the gut and its derivatives, and a parietal layer which contributes to the body wall. Since the celomic cavity does not extend into the most caudal portion of the embryo, the lateral plate mesoderm is not divided at this point. This represents Wyburn’s “secondary” layer mesoderm as it extends around the sides of the cloaca1 membrane splitting the ectoderm and endoderm. The deep part of this mesoderm contributes to the bladder musculature and the superficial part tc the infraumbilical body wall. If these lateral plates of mesoderm fail to fuse in the midline, the cloaca1 membrane will persist and eventually rupture creating an opening between the outside of the embryo and the cloaca or later the urogenital sinus (Fig. 4B). Glenister further maintains that the mesodermal layer
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FIGURE 6. Diagram illustrating disposition of mesoderm at caudal end of somite embryo. Observer is looking down into inside of caudal end of embryo. (1) Surface epithelium; (2) somatic layer of lateral plate mesoderm; (3) celomic cavity; (4) viseral layer of lateral plate mesoderm; (5) intermediate cell mass or nephrogenic cord; (6) somite; (7) neural tube; (8) notochord; (9) unsegmented paraxial mesoderm; (10) primitive streak; (11) site of developing urorectal septum; (12) site of definitive cloaca1 membrane; and (13) infraumbilical abdominal wall and site where mesois deficient in derm exstrophy of bladder (from Glenister, 1958lO).
Muecke12 reported similar results in 3 of 20 patients in their series. In view of these rather discouraging results, most authors now advocate urinary diversion and cystectomy as the treatment of choice. most encouraging results in Spence13 reported 31 patients treated by ureterosigmoidostomy with follow-up of five years in 22 and ten years or more in 16 of the patients.
that created a normal appearing abdominal wall in the cases studied by Paul and Kanagasuntheran was derived not from the unsegmented lateral mesoderm but from the somites of the lower thoracic region. In summary then, Wyburn’s “secondary” mesoderm fails to fuse in the midline leading eventually to rupture of the cloaca1 membrane. The somatic musculature of Paul and Kanagasuntheran can develop normally only as far as the margin of the cleft produced in the exstrophic bladder, therefore accounting for the normal development of the abdominal wall up to the medial border of the rectus sheath. Symptoms. Symptoms secondary to the anterior abdominal exteriorization of the bladder include saturation of the overlying clothing and excoriation of the skin surrounding the exposed bladder. Bleeding and edema of the exposed bladder mucosa is common, and this continuous irritation may lead to glandular cystitis and occasionally adenocarcinoma. Treatment. The results of primary closure of the bladder and urethra have been most discouraging. Lattimer and Smith” reported on 70 patients, 43 of whom were males. Only 3 patients in this series were continent of urine over two hours during the day. Marshall and
Just as exstrophy can occur without epispadias so too can epispadias occur without exstrophy. The association of incontinence with epispadias occurs only in the most severe form, the complete epispadias in which the entire dorsum of the urethra is open with the groove so formed involving the internal sphincter (Fig. 7). Epispadias has been estimated to occur once in 30,000 deliveries with males predominating three to one. Embryogenesis. As the “secondary” mesoderm of Wyburn develops, it extends around the margin of the caudal part of the infraumbilical membrane and gives rise to the paired phallic tubercles. Patten and BarryI suggested that as the phallic tubercles develop, they take up an
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FIGURE 7. i'ato c) First, second, and third-degree forms of epispadias in male. jd and e) Second and thirddegree forms of epispadias in female. First-degree epispadias is represented by bi$d clitoris. Only third-degree forms of epispadias which inooloe internal sphincter lead to incontinence in male and female (from Welch, K. I.,‘” used with permission).
abnormally caudal position with reference to the proctoderm (Fig. 5). When this occurs, the urorectal fold comes into direct contact with the genital tubercle. The urogenital sinus is thus positioned on the dorsal surface of the developing phallus rather than in its normal ventral location giving rise to an epispadic urethral groove (Fig. 4). S ymptoins. Complete epispadias gives rise to incontinence in both males and females. Because of the obvious epispadiac groove in the male, the diagnosis should seldom be missed. In the female the physical findings are less obvious and may lead to social ostracism and prolonged treatment for psychologic incontinence if allowed to go unrecognized. Surgical intervention should be Treatment. postponed until the child is about three years of age. A review of the literature indicates that continence can be restored in about 80 per cent of all cases of epispadias.15 In the remaining 10 per cent a urinary diversion may be necessary
FIGURE 8. Duplications of posterior urethra arising independently from bladder. (a to d) Complete separation of urethras. (e and ”f) Separate urethras , becoming confluent distally; (f) will not result in urethra joins normal incontinence since accessory (from Gray urethra proximal to external sphincter and Skandalakis16).
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because of deteriorating tinued incontinence.
renal function or con-
Duplication of urethra Duplication of the urethra represents the mildest anomaly of the infraumbilical body wall. Approximately 100 cases of urethral duplication have been reported in the literature. Although there are several variant forms of urethral duplications, those causing incontinence can be divided into two types (Fig. 8). First, complete duplication is represented anatomically by two completely separate urethras which extend from the bladder to the outside. One is the normal urethra, and the second is an accessory urethra which may open at any point along the phallus. Since the accessory channel may have no sphincter mechanism, some patients are incontinent of urine. Second, incomplete duplication anatomically is represented by an accessory urethra that originates in the bladder and empties distally into the normal urethra. If the opening is proximal to the external sphincter, the patient will remain continent. An opening distal to the external sphincter, however, will result in incontinence. Embryogenesis. As discussed in epispadias, the lateral anlage of the paired genital tubercles normally form a bridge across the ventral end of the cloaca1 membrane. When the tubercles unite in a posterior position in relation to the urorectal fold, the scene is set for the entire spectrum of congenital anomalies to develop, from exstrophy to incomplete duplication. Urethral duplication develops when the posterior displacement of the genital tubercles is less severe in position than that seen in epispadias and exstrophy. Accessory urethral channels that Symptoms. do not arise from the bladder may cause no symptoms whatsoever. Should the accessory channel originate in the bladder, however, total incontinence may be the presenting symptom associated with uremic excoriations of the skin.
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Total extirpation of the accessory Treatment. urethral channel is indicated in cases in which incontinence is manifested. Dorsal chordee often accompanies this lesion and should be corrected at the time of surgery. 1040 Main Street Danville, Virginia 24541 ACKNOWLEDGMENT. To Dr. M. W. Woodruff, Chairman, Division of Urology, Albany Medical College, for his support in the preparation of this article.
References 1. Begg RC: The urachus and umbilical fistulae, Surg. Gynecol. Obstet. 45: 165 (1927). 2. Nix JT, Menville JG, Albert M, and Wendt DL: Congenital patent urachus, J. Urol. 79: 264 (1958). 3. McCauley RT, and Lichtenheld FR: Congenital patent urachus, South. Med. J. 53: 1138 (1969). 4. Crenshaw JL: Ureter with extravesical orifice: supernumery ureter ending blindly; crossed ureteral ectopia; stones in extrapelvie cystocele; report of 11 cases, J. Ural. 43: 82 (1940). 5. Mills JC: Complete unilateral duplication of ureter with analysis of the literature, Ural. Cutan. Rev. 43: 444 (1939). 6. Arev LB: Develoumental Anatomv. 6th ed.. Philadelnhia. W. B. Saunders Co., 1954, p. 299. ” A 7. Campbell MF, and Harrison JH: Urology, 3rd ed., Philadelphia, W. B. Saunders Co., 1970, p. 1558. 8. Wybum GM: The development of the intra-umbilical portion of the abdominal wall with remarks on the etiology of ectopic vesicae, J. Anat. 71: 201 (1937). 9. Paul M, and Kanagasuntheran R: The congenital anomalies of the lower urinarv tract, Br. 1. Ural. 28: 64. 118 (1956). 10. Glenister TW: A correlation of the normal and ‘abnormal development of the penile urethra and of the intra-umbilical abdominal wall, ibid. 39: 117 (1958). 11. Lattimer JK, and Smith MJV: Exstrophy closure; a followup in seventy cases, J. Urol. 85: 356 (1965). 12. Marshall VF, and Muecke EC: Variations in exstrophy of the bladder, ibid. 88: 766 (1962). 13. Spence, HM: Ureterosigmoidostomy for exstrophy of bladder: results in personal series of thirty-one cases, Br. I. Ural. 38: 36 (1966). 14. Patten BM, and Barry A: The genesis of exstrophy of the bladder and eoisoadias. Am. 1. Anat. 99: 35 (1952). 15. Welch -Kjz Epispadias, in Mustard, ‘W. T., et al. Eds.: Pediatric Surgery, 2nd ed., Chicago, Year Book Medical Publishers, 1969, vol. 2, p, 1337. 16. Gray SW, and Skandalakis JE: Embryology for Surgeons, Philadelphia, W. B. Saunders Co., 1972, p. 527. 17. Cullen TS: Embryology-Anatomy and Diseases of the Umbilicus Together with Diseases of the Urachus. Philadelohia. I , W. B. Saunders Co., 1916, p. 488. 18. Seitzman DM, and Patten JF: Ureteral ectopia: combined ureteral and vas deferens anomaly, J. Urol. 84: 694 (1969).
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