Embryology and anatomy of the vesicoureteric junction with special reference to the etiology of vesicoureteral reflux

Abstract

Concerning the ureterovesical junction - the region most important for the anti-reflux mechanism - there is still a lot of misunderstanding and misinterpretation with regard to normal fetal development. Data are scarce on possible causes of primary vesicoureteral reflux and on involved mechanisms of the so-called maturation process of refluxing ureteral endings. The ratio of the intravesical ureteral length to the ureteral diameter is obviously lower than assumed so far, as clearly revealed by some studies. Therefore it can be doubted that the length and course of the intravesical ureter is of sole importance in the prevention of reflux. Additionally refluxing intravesical ureteral endings present with dysplasia, atrophy, and architectural derangement of smooth muscle fibers. Besides, a pathologically increased matrix remodeling combined with deprivation of the intramural nerve supply has been confirmed. Consequently, symmetrical narrowing of the very distal ureteral smooth muscle coat creating the active valve mechanism to defend reflux is not achievable. It is apparent that primary congenital vesicoureteral reflux seems to be the result of an abnormality within the ureterovesical junction with an insufficient muscular wrap. Nature is believed to establish much more sophisticated mechanisms than the so-called passive anti-reflux mechanism. Remodeling processes within the ureterovesical junction of refluxing ureteral endings support that maturation itself is nothing else than wound or defect healing and not a restitution of a morphological normal ureterovesical junction. Lacking the nerve supply a restoration of any muscular structure can not be achieved.

Keywords: children; extracellular matrix; human fetal development; nerve supply; ureterovesical junction; vesicoureteral reflux.

Figure 1.

An example of a plastination specimen clearly revealing the advantages of architectural integrity.

Figure 2.

Dimensions of distal ureter wall thickness, intravesical ureter wall thickness and length of intravesical ureter according to age groups.

Figure 3.

Ratio of tunnel length to ureteral diameter according to gestational age.

Figure 4.

Alpha-actin staining of a normal ostial ureter with predominantly inner longitudinal and slight outer circular layers of smooth muscle.

Figure 5.

Massive derangement of refluxive intravesical ureter showing severe absent smooth muscular wall (alpha-actin SM staining).

Figure 6.

Smooth muscle fascicle showing replacement of detoriated smooth muscle by connective tissue in perimysial and endomysial regions (myosin SM staining).

Figure 7.

Immunohistochemical staining for desmin demonstrating massive derangement of smooth muscle wall with disintegration and dissolving muscles fascicles.

Figure 8.

Illustration of MMP1, CD68 and S100 production in refluxing and normal ureteral endings including statistical significance at p < 0.05 (Mann-Whitney U test).