The Effect of Urothelial Damage on Ureteric Motility An Ultrastructural and Functional Study

Abstract

Evidence of a leaky urothelial barrier in bilharzial uropathy is presented. The ultrastructural basis of this concept is demonstrated together with its functional consequences. The study was conducted on 4 ureters obtained at surgery from patients with non-functioning kidneys due to chronic bilharzial infections. Six normal ureters from kidney donors served as controls. Light and electron microscopic studies showed a reduced thickness of the transitional epithelium together with localised disruption of intercellular junctions and infiltration of red blood cells. The functional studies involved in vitro demonstration of stable phasic peristaltic contractions which were fundamentally altered by the addition of urine. The changes in motility included increase in contractile frequency and elevation of basal tone, inducing a state of hypermotility which could be equated with ureteric spasm. These changes were partly reversible upon administration of the histamine l-blocker, mepyramine. Evidence is presented to show that these changes might be induced in vivo by histamine released from mast cells triggered by urine leaking through a damaged urothelial barrier. The functional consequences (pain, spasm) are discussed.

Distinctive Ultrastructural Pathology of Nonulcerative Interstitial Cystitis

“…84], It is doubtful, however, that such focal leakiness is more than a subsidiary or sup plementary cause of the generalized fluid clogging of uro thelium in 1C described in the present study. Nor is it like ly to be the primary pathogenetic factor in 1C [84], An ultrastructural appearance of urothelium very similar to that we observed in IC has been described in the bilharzial ureter [101]. The vesical urothelium of the elderly also has a discohesive, fluid-clogged appearance and focally dis rupted umbrella cells components of the permeability bar rier [43], but lacks the other ultrastructural changes in blood vessels, nerves, and muscularis described in the present study [Hailemariam et ah.…”

“…Urine gaining access into the bladder wall through a locally leaky urothclium would create a hyper osmolar, ion-rich environment that can modify neurally triggered muscle cell responses or trigger responses inde pendent of neural activity. Parenthetically, such a hyper osmolar environment can release mediators from mast cells, stimulate pain fibers, and activate matrix synthesis by fibroblasts [101], Edema of muscle cells together with their tight crowding and occasional ultraclosc abutment junctions, providing the medium for both mechanical and much faster electrical coupling of muscle cell contraction [54], in addition to altered neuroeffector transmission, would create a detrusor that is hvpcrirritable and highly responsive to reflex excitatory neural stimuli, resulting in extreme frequency and urgency.…”

Deficiency of Pdcd10 causes urothelium hypertrophy and vesicle trafficking defects in ureter

“…In bladder, exocytosis is essential for the regulation of cell surface area during bladder filling and voiding cycles [7,9]. While characterization of the ultrastructure and membrane trafficking within the bladder urothelium is well documented [7,8,[10][11][12][13], there remains a paucity of equivalent information for the ureter urothelium [14][15][16].…”