DISRUPTION OF GUINEA-PIG URINARY-BLADDER PERMEABILITY BARRIER IN NONINFECTIOUS CYSTITIS

Although most cell membranes permit rapid flux of water, small nonelec trolytes, and ammonia, the apical membranes of bladder epithelial umbr ella cells, which form the bladder permeability barrier, exhibit strik ingly low permeabilities to these substances. In cystitis, disruption of the bladder permeability barrier may irritate the bladder wall laye rs underlying the epithelium, causing or exacerbating inflammation, an d increasing urinary frequency, urgency, and bladder pain. To determin e the effects of inflammation on the integrity of the permeability bar rier, guinea pigs were sensitized with ovalbumin, and the bladders wer e exposed subsequently to antigen by instillation on the urinary side. Inflammation of the bladder wall markedly reduced transepithelial res istance of dissected epithelium mounted in Ussing chambers and increas ed water and urea permeabilities modestly at 2 h and more strikingly a t 24 h after induction of the inflammation. Transmission and scanning electron microscopy of bladders at 30 min and 24 h after antigen expos ure revealed disruption of tight junctions, denuding of patches of epi thelium, and occasional loss of apical membrane architecture. These pe rmeability and structural effects did not occur in nonsensitized anima ls in which the bladders were exposed to antigen and in sensitized ani mals exposed to saline vehicle rather than antigen. These results demo nstrate that inflammation of the underlying muscle and lamina propria can disrupt the bladder permeability barrier by damaging tight junctio ns and apical membranes and causing sloughing of epithelial cells. Lea kage of urinary constituents through the damaged epithelium may then e xacerbate the inflammation in the underlying muscle layers.