Every beest that gendreth hath a bladder. TREVISA Barth. De P.R.v.xliv (1495) 161, 1398.
Because a man should do something else besides continually piss, the bladder was added to containe the urine.N. CULPEPER Culpeper’s Last Legacy. London, N. Brook, 1661 .
Development of the bladder
Formation of hindgut and allantois
During the blastocyst stage, the fetus lies within the amniotic cavity . As the yolk duct becomes obliterated, an outgrowth of the yolk sac forms the allantoenteric diverticulum within the connecting stalk that joins the fetus to the placenta . The cloacal plate is formed dorsal to the connecting stalk ( Fig. 13-1 ).
Incorporation of the allantoic duct into the hindgut
The cloaca is that portion of the gut caudal to the opening of the allantoenteric diverticulum . The endodermal ventral lip of the cloaca makes contact with a patch of ectoderm of the body wall as the intervening mesoderm of the cloacal plate becomes thinned and is moved aside. This fused area of endoderm and ectoderm is the cloacal membrane . The membrane becomes oriented at an angle with the long axis of the embryo, defining the end of the primitive hindgut, and acts as a guide for the development of the region ( Fig. 13-2 ).
Cloacal membrane and the cloaca
The cloacal membrane becomes oriented even more in the frontal plane, defining the cloaca behind it. The membrane extends cephalad from the opening of the allantoenteric diverticulum to the caudal end of the cloaca ( Fig. 13-3 ).
Incorporation of the allantoenteric diverticulum
At about 28 days, the dorsal section (enteric part) of the allantoenteric diverticulum moves dorsally, so that the diverticulum opens into the cloaca cephalad to the persisting portion of the cloacal membrane ( Fig. 13-4 ). The membrane becomes oriented in a still more coronal plane, resulting in a deeper cloaca. As the cloaca elongates caudally with growth of the tail, so does the cloacal membrane, until it constitutes the whole of the ventral wall of the cloaca.
The urorectal septum
By the middle of the fourth week of gestation, the cloacal membrane has been moved caudally by encroachment of abdominal mesoderm and is ready to play a role in urogenital differentiation. The hindgut can be recognized proximal to the cloaca and the tailgut distal to it.
At this time, a saddle appears between the allantoenteric duct and the intestinal opening of the cloaca ( Fig. 13-5 ). This saddle develops into the urorectal septum , which descends as a partition between the ventral portion of the cloaca, destined to become the rudimentary bladder, and the dorsal portion, the hindgut. This places the allantoenteric duct at the ventral end of the future bladder.
Ectodermal and endodermal cloacas
As the urorectal septum divides the endodermal cloaca into the urogenital sinus and the hindgut (see Fig. 13-7 ), the cloacal membrane appears to subside into the ventral mesenchyme because of mesodermal growth around it. This leaves a shallow depression lined with ectoderm on the ventral surface, the ectodermal cloaca , from which the external genitalia and perineum will form ( Fig. 13-6 ). The space on the dorsal side of the cloacal membrane constitutes the endodermal cloaca .
Mechanism of cloacal division
The cloaca is divided by a combination of direct downward progression of the urorectal septum into the cloaca and intrusion of folds from each side of it. Disturbance in this division is an important factor in the production of anorectal anomalies.
A tongue of mesenchyme extends caudally, forming the leading edge of the descending urorectal fold of Tourneaux (arrow T ) ( Fig. 13-7 A). The shape of the tongue is concave because the lateral edges develop more rapidly than the center. It descends in the coronal plane but does not reach the cloacal membrane .
In addition to the descent of the tongue, a pair of folds press in laterally as the urorectal folds of Rathke (arrows R ) ( Fig. 13-7 B). Rathke’s folds unite in the midline and complete the urorectal septum, extending it from the ventral end of the urorectal fold of Tourneaux to the cloacal membrane.
The urorectal septum fuses with the cloacal membrane to complete the separation of the urinary tract into the urogenital sinus from the gut and the anal canal ( Fig. 13-7 C).
Vesicourethral canal and urogenital sinus
By 7 weeks, the cloaca has been separated into the urogenital sinus anteriorly and the anal canal and rectum posteriorly. Contact of the urorectal septum with the cloacal membrane separates it into an anterior urogenital membrane and a posterior anal membrane ( Fig. 13-8 A). The urogenital membrane will open as the urogenital orifice, and the anal membrane will become similarly perforated to form the anus. The urogenital sinus subsequently becomes divided into three portions. The part continuous with the allantois and extending distally to the site of entrance of the wolffian (mesonephric) ducts at the müllerian tubercle forms the vesicourethral canal . The narrower middle portion constitutes the pelvic part of the urogenital sinus. The wider distal portion, the phallic part , extends to the urogenital membrane.
In the next week, the bladder and proximal urethra take form from the vesicourethral canal.
The bladder and proximal urethra are derived from two sources, even though they appear as one continuous structure ( Fig. 13-8 B). The bladder arises mainly from the endoderm of that portion of the urogenital sinus forming the vesicourethral canal , but parts of the proximal urethra and trigone are formed from mesoderm arriving during the incorporation of the end of the wolffian duct .
The urogenital sinus portion of the cloaca distal to the vesicourethral canal becomes reconfigured; its more proximal tubular portion becomes the pelvic part of the sinus, the site of the prostatic urethra, and the distal flattened portion, the phallic part , makes up the remainder of the urethra.
The bladder is represented initially by the elongated upper portion of the vesicourethral canal. The lumen of this upper segment gradually enlarges compared with the narrow urethral portion, and the epithelial cells from the endoderm lining the bladder segment become larger as well. The surrounding mesenchyme, starting at the dome, differentiates into an outer connective tissue layer. In this layer, strands of smooth muscle form with little specific orientation, although three interlaced layers (inner longitudinal, middle circular, and outer longitudinal) can be identified relatively early in development. Later and independently, muscular development takes place at the base, being particularly abundant under the trigone and at the bladder neck, where the fibers take a more circular path to form the internal vesical sphincter. This portion of the bladder is also distinct from the dome because of its separate nerve supply as it acquires sympathetic innervation in contrast to the parasympathetic nerves that supply the detrusor.
By 13 weeks, the vesical neck has been formed and the bladder changes from an oval to a triangular shape.
The bladder lies within the anterior abdominal wall until the seventh week, when it is crowded out of the pelvis by the enlarging umbilical arteries on either side. It moves into the abdominal cavity on a temporary mesentery formed from the loose mesenchyme containing the urachus and umbilical arteries. The mesentery is present into the seventh month, during the time that the bladder remains in the abdominal cavity. The bladder gradually descends into the pelvis in late fetal life and early infancy, although at birth, because of the underdevelopment of the true pelvis, it still is essentially an abdominal organ. In the first 2 postnatal years, its descent into the pelvis is rapid, then it slows to become complete at the age of 20 years.
The umbilical vesical fascia , evolving from the temporary mesentery, is formed from the intermediate stratum of the retroperitoneal tissue. It extends cephalad to the umbilicus to enclose the urachus and the umbilical arteries and caudally to cover the bladder, seminal vesicles, and the prostate. Lateral condensations form the lateral true ligaments of the bladder and the puboprostatic ligaments (see Fig. 13-52 ).
Sinoutricular cord, verumontanum, and formation of the prostatic utricle
As the tips of the fused and canalized müllerian (paramesonephric) ducts meet the urogenital sinus , they stimulate the sinus epithelium to form a protuberance into the sinus, the müllerian tubercle or verumontanum ( Fig. 13-9 A).
A second protuberance develops in the direction of the duct on the outside of the urogenital sinus. This projection is joined to the fused müllerian ducts to form the sinoutricular cord ( Fig. 13-9 B).
In the male, the distal portion becomes canalized to form the prostatic utricle or vagina masculina. In the female, this part forms the distal part of the vagina ( Fig. 13-9 C).
Ureterovesical junction and trigone
Incorporation of the common excretory duct
The mesodermal common excretory duct is defined as that portion of the wolffian duct distal to the ureteral bud ( Fig. 13-10 A). The tissue of the endodermal vesicourethral canal expands posteriorly toward the common excretory duct to form, in combination with the terminal piece of the common excretory duct, a funnel-shaped extrusion, the cloacal horn .
As the cloacal horn becomes reincorporated into the canal, it carries the terminal piece of the common excretory duct into the vesicourethral canal with the ureter attached and forms part of the superficial trigone ( Fig. 13-10 B). Another interpretation has the bladder wall intussuscept the wolffian duct to draw the ureter into the bladder because the cloacal horn looks like an intussusception as it is reincorporated.
The ureter had originally branched from the dorsal aspect of the wolffian duct, but during incorporation, the ureteral orifice changes position so that it is brought into the bladder wall directly lateral to the orifice of the wolffian duct .
The formation of the superficial trigone begins with the fusion of the mesoderm medial to the two ducts ( Fig. 13-10 C).
Although the orifice of the wolffian duct remains in place, the mesoderm that was originally part of the common excretory duct becomes active and enlarges. This mesodermal growth displaces the ureteral orifices cranially and laterally, shifting them from near the midline at the junction of the vesicourethral canal with the urogenital sinus into a lateral position in the bladder . The entire superficial trigone, a structure that extends from the verumontanum to the ureteral orifices, is formed by this mesodermal (wolffian) growth.
Incorporation of the common excretory duct
The steps of incorporation are shown in three sets of drawings: Figs. 13-11 A and B each have a coronal, sagittal, and frontal view. Figure 13-11 C shows a frontal and a sagittal view. A dashed line across each frontal view indicates the original level where the wolffian duct made contact with the vesicourethral canal, defining the junction of the canal with the urogenital sinus.
The common excretory ducts and the future ostium of the fused müllerian ducts enter the vesicourethral canal on the verumontanum (müllerian tubercle) ( Fig. 13-11 A). The ureteral buds branch from the wolffian duct proximal to the common excretory duct, which is continuous with the cloacal horn that was derived from the tissue of the canal.
With the incorporation of the cloacal horn and the common excretory duct into the vesicourethral canal, the wolffian duct and the ureter enter side by side ( Fig. 13-11 B). The ureteral orifice enters lateral to the orifice of the ejaculatory duct. The terminal portion of the müllerian duct, now the prostatic utricle, opens between them.
The growth of mesodermal wolffian tissue (cross-hatched area) between the orifices of the ureter and the ejaculatory duct, combined with expansion of the bladder wall, results in the ascent and lateral displacement of the ureteral opening ( Fig. 13-11 C). In contrast, the opening of the wolffian duct is fixed in position at the verumontanum, not only from its close embryologic association with the müllerian duct but also because the entire lower portion of the urogenital sinus is fixed in solid mesodermal condensations so that expansion can occur only in a cephalic direction. The terminations of the wolffian ducts do, in fact, move a small distance cephalad, leaving a symmetric pair of longitudinally disposed remnants as collicular folds . The dashed line shows the level at which the wolffian duct originally made contact with the vesicourethral canal. The length of the collicular folds is an indication of the distance that the ducts and verumontanum have moved cephalad.
In the mature stage, the tissue from the wolffian duct forms the superficial trigone. The ureteral orifice lies at its proximal extremity. Distally, in the preprostatic urethra, the verumontanum is found holding the ejaculatory ducts and prostatic utricle. Thus developmentally the muscles of the superficial trigone are continuous with those of the ureter, all being of wolffian origin.
Ductal incorporation in male and female
Male
The ductal mesoderm (cross-hatched area) that was incorporated into the vesicourethral canal moves cranially and laterally and carries the ureteral orifices with it. As described previously, this tissue becomes distributed as the superficial trigone in the area between the ejaculatory ducts distally and the ureteral orifices proximally. At this stage, the kidney has become organized but the mesonephros remains lateral to the gonad ( Fig. 13-12 A). The fused müllerian ducts enter the canal at the verumontanum, which lies at the junction of the vesicourethral canal and the urogenital sinus. The ureters penetrate the bladder wall by a straight course; later development provides an oblique tunnel.
Female
The wolffian mesoderm is incorporated as in the male ( Fig. 13-12 B). Instead of resulting in a prostatic utricle, canalization of the sinoutricular cord in the female forms the terminal portion of the vagina (see Fig. 13-9 ). The entire female urethra develops from the urogenital sinus as the homologue of the posterior urethra of the male. The equivalent of the verumontanum containing the müllerian prostatic utricle could be viewed as lying at the introitus (see Fig. 15-6 ). Remnants of the wolffian ducts become the epoöphoron and paroöphoron, and are also represented in the adult as the Gartner ducts that extend the length of the vagina (see Fig. 15-3 ).
Anomalies of the ureterovesical junction
Anomalies are common near the junction of the ureter with the trigone, resulting from the variations in the budding of the ureteral bud from the wolffian duct. They may be duplications consequent on the formation of a second bud on the wolffian duct or they may be ureteral ectopia from late arrival or vesicoureteral reflux from early arrival of the ureter at the vesicourethral canal.
Even if the ureteral bud forms at the proper place and time, it may be unduly large and result in formation of a dilated upper tract such as is seen in the nonrefluxing nonobstructed megaureter (see Fig. 13-28 ). The bud may not elongate (renal ectopy), it may not grow or have sufficient inductive ability (blind ending ureter and hypoplastic kidney), or it may divide before it has reached the nephrogenic blastema (renal duplication and triplication).
An inadequate response of the renal blastema to the stimulus arising from the branching ureteral bud may also result in a reduction of renal tissue. Renal dysplasia or dysgenesis (bad molding or bad generation) are not clearly defined as embryologic entities. They may be associated with obstruction but can occur in inheritable syndromes in the absence of obstruction. Renal dysplasia may be due to lack of inductive capacity in a ureteral bud. Or the bud may develop in a relatively abnormal position so that it attempts induction of a deficient region of the renal blastema. Evidence for this is that dysplasia is commonly found associated with a displaced secondary ureteral bud that empties laterally or distally into the urethra.
Anomalies at the ureteric hiatus
Paraureteral diverticula (saccules) arise at the upper extremity of the trigone just above the ureteric orifice as a transhiatal herniation of the bladder mucosa. Some are congenital, because they are found in the fetus and are not necessarily associated with obstruction. Deficient development of the hiatus and of the muscle of the superficial trigone is the probable cause in infants. Many are probably secondary to a weak inner longitudinal layer of the bladder musculature at the ureterovesical angle and to poor support from the outer longitudinal layer ( Fig. 13-13 ).
With obstruction or neurogenic bladder, increased detrusor pressure may cause transhiatal herniation of the vesical mucosa to form the so-called saccule of mucosa forced through an overstretched hiatus. Hiatal diverticula disturb the submucosal course of the terminal ureter and, therefore, are associated with reflux.
True diverticula may be present on a purely congenital basis; these will have some muscle strands in the wall.
Ureterocele
A ureterocele is a cystic dilation of the terminal ureter. How it develops is not well understood. One explanation is delayed rupture of the occluding epithelial membrane normally lying at the junction of the ureter and the urogenital sinus in the sixth week of gestation, when nephrogenic function is in abeyance; persistence of the membrane leads to obstruction at that site. Another explanation is delay in the absorption of the immature ureter into the vesicourethral canal (see Fig. 13-10 ). A third theory is that arrest in muscular development of a ureter situated too far caudally results in distention of the terminal portion.
A simple ureterocele, in which the cystic formation occurs at the site of the normal orifice, is rare in children and may actually be acquired rather than congenital ( Fig. 13-14 ).
With ectopic ureterocele, the orifice lies between the normal position and the urethral sphincter, an anomaly that is five times more common in girls ( Figs. 13-15 , 13-16 , 13-17, and 13-18 ). A distinction is made between an intravesical ureterocele, in which the orifice is within the bladder, and an ectopic ureterocele extending distal to the bladder neck, although its orifice may lie in the bladder. Three types have been described. The simple stenotic type is intravesical and has a muscular wall with a narrow orifice on its summit. In the sphincteric type of ureterocele, the orifice lies within the internal vesical sphincter and empties only during voiding. A sphincterostenotic orifice forms the third type, having features common to the other two types.
Illustrated in Fig. 13-19 are a simple ureterocele (stenotic type) and an ectopic ureterocele (sphincteric type) draining a dilated upper renal segment. The opening of the ectopic ureter into the ureterocele is, as expected, distal to that of the orthotopic ureter. The orifice of the ureterocele in this case lies in the bladder neck.
Ureteral duplication
The ureter may be duplicated with both orifices lying together in an essentially normal position or one orifice may be ectopic. A single ureter with a single orifice may be displaced into an ectopic position by the same embryologic mechanism associated with a second duplicated ureter. The important factor is the time of arrival of the ureteral orifices at the vesicourethral canal and the differential growth of the wolffian mesoderm of the posterior wall of the canal.
Use of the terminology proposed by the Committee on Terminology, Nomenclature and Classification, Section on Urology, American Academy of Pediatrics avoids confusion in describing duplication anomalies. A duplex kidney has two pyelocaliceal systems. A bifid renal system has two pelves joined at the ureteropelvic junction, forming a bifid pelvis . A bifid ureter consists of two ureters joined above the ureterovesical junction. Double ureters are two completely duplicated ureters ( Figs. 13-20 and 13-21 ). A lower pole ureter drains the lower pole of a duplex kidney through a lower pole orifice that is in the normal ( orthotopic ) position at the lateral corner of the trigone. An upper pole ureter drains the upper pole via an upper pole orifice that is ectopic , draining onto the trigone distal to the site of the orthotopic orifice or beyond the proximal lip of the vesical neck. In the male, the most distal position of an ectopic orifice is the verumontanum; in the female, it is the introitus ( Figs. 13-22 and 13-23 ). Ectopic ureters initially follow the same course as the orthotopic one through the bladder wall and pass through the usual submucosal tunnel but take an abnormal course more distally.
Ureteral duplication with ectopic orifice
The final site of the ureteral orifice depends on the original site of the bud from the wolffian duct. Typically, the ectopic orifice of a double system will lie in the bladder or urethra distal to the orthotopic one. Stephens has shown that there is an “ectopic pathway” that includes not only sites distal to the normal orifice but medially and superiorly to it. However, orifices in the latter positions would violate the Weigert-Meyer rule (see later section).
In Fig. 13-24 , the dotted line indicates the level at which the wolffian duct joined the urogenital sinus. It marks the junction of the vesicourethral canal with the urogenital sinus.
With two separate ureteral buds developing from the common excretory duct (dark cross-hatched area), one ureteral bud (black) branches proximally from the duct and makes connection with the upper pole of the nephrogenic blastema as the upper pole ureter ( Fig. 13-24 A). The second bud (hatched area) branches from the common excretory duct distally, nearer the vesicourethral canal, and enters the lower pole of the blastema as the lower pole ureter.
As the common excretory duct (dark cross-hatched area) becomes incorporated into the vesicourethral canal to form the superficial trigone, the more distal portion of the common excretory duct to which the lower pole ureter (hatched area) is attached is the first to join the canal ( Fig. 13-24 B). As it becomes implanted lateral to the wolffian duct orifice, it is the first of the two ureteral orifices to be carried proximally and laterally on the expanding trigone.
The upper pole ureter arrives late because it remained attached to the duct for a longer time and has farther to go ( Fig. 13-24 C). When it joins the canal, much of the superficial trigone has been formed and the orifice of the lower pole ureter has already been moved proximally.
As the common excretory duct becomes totally incorporated and the formation of the trigone is completed, the orifice of the upper pole ureter remains distal to that of the lower pole ureter because it arrived too late to be carried cephalad by the growth of the ductal mesoderm ( Fig. 13-24 D).
This reversal of the upper-lower relationship vis-à-vis the kidney and bladder is incorporated in the Weigert-Meyer rule: with duplication, the ureter from the upper pole terminates more distally than that from the lower pole. Rare exceptions to the rule can be explained by the premature division of a single bud, so that both buds arrive at the sinus at the same time.
Should the second ureteral bud not separate but remain attached to the duct, it will empty with it at the verumontanum. It cannot terminate in the urethra more distally than at this site, although it may end in one of the wolffian duct derivatives, such as the ejaculatory duct or seminal vesicle. If the wolffian duct fails to separate from the ureteric bud as the ureter is incorporated into the vesicourethral canal, an ectopic vas deferens may empty into the ureter.
In the female, the wolffian duct is represented by the Gartner duct, which becomes incorporated into the vaginal wall. The “verumontanum” may be visualized as lying beyond the introitus, which is the homologue of the prostatic utricle. Thus the ureteral orifice may empty into the urethra along the course of the Gartner duct distal to the sphincter. It may also end in a derivative of the müllerian duct (uterus, cervix, or vagina), with resulting incontinence. These connections to the female genital tract are explained by the close association of the müllerian and wolffian ducts during development of the urogenital sinus. It has been postulated that the ureter at first ends blindly in these structures and that the accumulation of urine then forces an opening to the exterior, with resulting urinary incontinence.
Ectopic ureteral orifice with a single system
The ureteral bud forming the ureter (black) has branched from the common excretory duct (dark cross-hatched area) more proximally than normal, in a position similar to that of the upper pole ureter in a duplication anomaly ( Fig. 13-25 A; see also Fig. 13-24 ).
As the common excretory duct is incorporated into the vesicourethral canal, the ureter will arrive late. Losing the opportunity to ascend with the generating wolffian tissue, it will open through an ectopic orifice into the canal at a site distal to the orthotopic orifice ( Fig. 13-25 B).
Primary reflux
Primary reflux may be explained by a ureteral bud that arises abnormally low from the wolffian duct, producing a short common excretory duct , which is just the opposite of what occurs in ureteral ectopy ( Fig. 13-26 A).
The early arrival of the bud at the vesicourethral canal allows extra time for craniolateral migration of the ureter in the enlarging wolffian mesoderm. The result is a large trigone and a lateral ectopic orifice that is displaced proximally and laterally ( Fig. 13-26 B). Because the common excretory duct was short and so contributed less mesoderm to the formation of the trigone, the superficial trigone, as well as the intramural ureter, may be less well developed and consequently less able to maintain ureteral obliquity during voiding ( Fig. 13-27 ).
