The morphology of normal human bladder urothelium

A comprehensive study of human bladder urothelium was undertaken to define the normal histological and fine structural features of this tissue. Urothelial biopsies from consenting male and female patients undergoing diagnostic or review cystoscopies were analysed. In 31 patients there was an apparently normal urothelium lining the bladder, and in 3 patients the trigone appeared normal. Normal urothelium was not observed to contain lymphocytes, lymphoid follicles, mast cells, Brunn's nests or cysts. No mitoses were seen despite examining about 50,000 urothelial cells. Trigonal and bladder urothelium normally consisted of 3 and 3-6 cell layers, respectively, but they shared the same basic architecture of basal, intermediate and superficial (or surface) cell types. The urothelium possessed a regular, polarised architecture of increasing morphological complexity and differentiation from base to surface. Occasional, slender, cytoplasmic projections were observed to reach the basal lamina from the intermediate cell layer, but not from the surface cell layer. Human urothelium should therefore be considered a stratified, not a pseudostratified, epithelium. The nuclear shape in cross-section was indented in the basal layer, and rounded in the superficial layer. Correspondingly, chromatin configurations of urothelial nuclei were evenly and finely granular in the superficial layer and condensed in the basal layer, suggesting a greater degree of transcriptional activity in the former. Intermediate cell nuclei assumed intermediate degrees of shape and chromatin configuration. Prominent nucleoli were found in the nuclei of all cell layers. Both basal and intermediate cell nuclei and superficial cell nuclei contained characteristic nuclear bodies. Urothelial cells of all layers were connected by interdigitations of cytoplasmic processes and by desmosomes. Clusters of mitochondria were seen throughout the urothelium. Elaborate Golgi membranes and rough endoplasmic reticulum, although rare in the basal layer, were observed in the remainder of the urothelium. Large, prominent lysosomes were identified with the electron microscope and histochemically in the surface layer. The superficial aspect of the urothelium was lined, at least in some regions, by an asymmetric luminal membrane. Tight junctions linked adjacent urothelial surface cells. Such junctions were not observed anywhere else in the urothelium. Fine cytoplasmic filaments, probably of the intermediate type, were most conspicuous in the surface layer. Overall, normal human bladder urothelium is arranged in increasing complexity from base to surface.