Permeability and Ultrastructure of Human Bladder Epithelium

Eldrup, J; Thorup, Jørgen; Nielsen, Steen Levin; Hald, T; Hainau, Bo

doi:10.1111/j.1464-410x.1983.tb03354.x

Cited by 97 publications

(70 citation statements)

References 11 publications

(8 reference statements)

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“…The herein observed changes in urothelium confirm and considerably supplement those described previously in a few studies [29,40,41], The combined architectural and cytologic nature of these changes strongly suggests break of the urothelial permeability barrier. i.e" a leaky urothe lium.…”

Section: Discussionsupporting

confidence: 78%

Distinctive Ultrastructural Pathology of Nonulcerative Interstitial Cystitis

Jk²

1996

Urol Int

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Ultrastructural study of the bladder in interstitial cystitis has, so far, been limited, mainly to the urothelium. The present study was conducted first to study in detail the ultrastructural features of all tissue components of the bladder wall in nonulcerative interstitial cystitis and second to derive clues from the observed changes to pathogenesis of the disease. Endoscopic biopsies of urothelium with attached suburothelium, and muscularis, were obtained from both lesional and nonlesional areas in 5 female patients with unequivocal clinical diagnosis of interstitial cystitis. The specimens were processed for electron microscopic study by standard methods and subjected to comprehensive ultrastructural study of urothelium, suburothelium, detrusor muscle cells, intrinsic blood vessels, and intrinsic nerves. A distinctive combination of peculiar muscle cell profiles, injury of intrinsic vessels and nerves in muscularis and suburothelium, and discohesive urothelium was observed in lesional and less markedly in nonlesional samples of all specimens. Marked edema of various tissue elements and cells appeared to be a common denominator of many observed changes. Edema of muscle cells resulted in characteristic querciphylloid profiles, so designated because of peripheral bosselation of cell sarcoplasm with a lobed perimeter resembling that of an oak leaf. Urothelial changes disrupted the true permeability barrier, consisting of asymmetric unit membrane and triple epithelial junctions of surface (umbrella) cells. Vascular lesions included endothelial cell injury and suggested sluggishness of intrinsic microcirculation. Neural changes included a combination of degenerative and regenerative features, some expressing neural plasticity. The observed ultrastructural changes appear to be sufficiently distinctive to be diagnostic in specimens submitted for pathologic confirmation of nonulcerative interstitial cystitis. The changes do not support a primary pathogenetic role of mast cells or a selectively deficient glycosaminoglycan layer. They do suggest, however, a pathogenesis based on a potentially self-perpetuating process of neurogenic inflammation that can trigger a biologically potent cascade of events, including a leaky urothelium and mast cell activation. As proposed, neurogenic inflammation consolidates various proposals advanced as the pathogenesis of interstitial cystitis and can readily accommodate infectious, immunologic, and autoimmunologic mechanisms as factors that contribute to development or chronicity of the disease.

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Section: Discussionsupporting

confidence: 78%

Distinctive Ultrastructural Pathology of Nonulcerative Interstitial Cystitis

Jk²

1996

Urol Int

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“…Parsons (22) demonstrated that IC patients absorbed over six times as much urea instilled into the bladder compared with controls. Eldrup and coworkers (5) showed consistent leakage through tight junctions in IC patients. Buffington (2) showed abnormal excretion of injected fluorescein by IC patients suggestive of recycling due to absorption of the dye through the bladder.…”

mentioning

confidence: 93%

“…Much controversy has resulted over what structures or molecules are responsible for the impermeability of the bladder and what happens in IC to increase permeability and whether it is a cause or an effect (16). Candidates include the uroplakin layer (11) and the GAG layer (5) on the luminal surface and tight junctions (5).…”

mentioning

confidence: 99%

In the absence of overt urothelial damage, chondroitinase ABC digestion of the GAG layer increases bladder permeability in ovariectomized female rats

Hurst

Gordon

Tyler

et al. 2016

American Journal of Physiology-Renal Physiology

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In the absence of overt urothelial damage, chondroitinase ABC digestion of the GAG layer increases bladder permeability in ovariectomized female rats. Am J Physiol Renal Physiol 310: F1074 -F1080, 2016. First published February 24, 2016 doi:10.1152/ajprenal.00566.2015.-Loss of integrity of the protective impermeability barrier in the urothelium has been identified as significant in bladder dysfunction. In this study, we tested the theory that the luminal layer of glycosaminoglycans (GAG) serves as an important component of barrier function. The peptide polycation protamine sulfate (PS), 1 mg/ml, was instilled intravesically for 10 min into rat bladders. Chondroitinase ABC (ChABC), 63 IU/ml, was instilled into an additional six rats for 30 min to digest the GAG layer. Unmanipulated controls and sham-injected controls were also performed. After 24 h, the rats were euthanized, the bladders were removed, and permeability was assessed in the Ussing chamber and by diffusion of FITC-labeled dextran (4 kDa) to measure macromolecular permeability. The status of tight junctions was assessed by immunofluorescence and electron microscopy. In control and sham treated rat bladders, the transepithelial electrical resistance were means of 2.5 Ϯ 1.1 vs. 2.6 Ϯ 1.1 vs 1.2 Ϯ 0.5 and 1.01 Ϯ 0.7 k⍀·cm 2 in the PS-treated and ChABC-treated rat bladders (P ϭ 0.0016 and P ϭ 0.0039, respectively). Similar differences were seen in dextran permeability. Histopathology showed a mild inflammation following PS treatment, but the ChABC-treated bladders were indistinguishable from controls. Tight junctions generally remained intact. ChABC digestion alone induced bladder permeability, confirming the importance of the GAG layer to bladder barrier function and supports that loss of the GAG layer seen in bladder biopsies of interstitial cystitis patients could be a significant factor producing symptoms for at least some interstitial cystitis/painful bladder syndrome patients. urinary bladder; administration; intravesical; cystitis; interstitial; permeability; models; animal INTERSTITIAL CYSTITIS (IC) is a disease of the bladder diagnosed by exclusion on the basis of urgency, frequency, and pain (6). Although the etiology of this disease remains unknown, the evidence suggests that there is disruption of the urothelium that could result in enhanced bladder permeability (9,17,22,31). For the IC patient, the presence of urine is responsible for inflammation and pain in addition to promoting thinning and sloughing of the urothelium and distinct changes in the muscle (21,27,30). A high proportion of IC patients show loss of chondroitin sulfate from the luminal surface of the urothelium as well as abnormalities in uroplakin, the cell adherence protein E-cadherin, and ZO-1, the molecule in the zona occludens that links cells together (9). The identification of comorbitities that appear frequently with IC has suggested that the bladder symptoms are part of a wider spectrum of symptoms denoted by chronic pelvic pain (CPP) or IC/painful bladder syndrome (IC/...

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“…In the current study we observed focal loss of the urothelial layer, and loss and irregularity of the GAG layer in most areas, similar to the studies of Parsons et al [3,30,32] and Quinton and Philpott [3] . Other studies in patients with IC showed an increased epithelial permeability, explained by the defect in tight junctions [33] . SEM observations in patients with IC showed a decrease in the mucous layer, degeneration of cell junctions and increase in the number of microvilli [33] .…”

Section: Discussionmentioning

confidence: 99%

“…Other studies in patients with IC showed an increased epithelial permeability, explained by the defect in tight junctions [33] . SEM observations in patients with IC showed a decrease in the mucous layer, degeneration of cell junctions and increase in the number of microvilli [33] . Our light microscopy and SEM observations showed a decrease in the mucous layer, dilatation of the superficial cells and ulcerated areas at the apical surface.…”

Section: Discussionmentioning

confidence: 99%

Aqueous Garlic Extract Inhibits Protamine Sulfate-Induced Bladder Damage

Zeybek

Çikler²,

Sağlam³

et al. 2006

Urol Int

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This morphological and biochemical study aims to investigate the antioxidant effects of chronic administration of aqueous garlic extract (AGE) on protamine sulfate (PS)-induced bladder injury. Wistar albino female rats were catheterized and intravesically infused with phosphate-buffered solution (control group) or PS (PS group) dissolved in phosphate-buffered solution. In the PS + AGE group after the PS instillation, AGE (1 ml/kg, i.p., corresponding to 250 mg/kg) was injected intraperitoneally for 3 days. Bladder morphology was investigated by light and scanning electron microscopy. Tissue samples were also obtained to determine bladder malondialdehyde (MDA) and glutathione levels. In the PS group, ulcerated areas, an irregular mucus layer, inflammatory cell infiltration and an increased number of mast cells were observed. In the PS + AGE group a relatively normal urothelial topography, glycosaminoglycan layer and a decreased number of mucosal mast cells and inflammatory cells were observed. Increased MDA levels as a result of PS induction led us to propose that free radicals may have a critical role in this injury. The significant decrease in MDA and increase in glutathione levels in the PS + AGE group was in accordance with morphological findings. Based on the results, AGE treatment significantly prevented PS-induced degenerative morphological and biochemical changes of urinary bladder mucosa.

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Permeability and Ultrastructure of Human Bladder Epithelium

Cited by 97 publications

References 11 publications

Distinctive Ultrastructural Pathology of Nonulcerative Interstitial Cystitis

Distinctive Ultrastructural Pathology of Nonulcerative Interstitial Cystitis

In the absence of overt urothelial damage, chondroitinase ABC digestion of the GAG layer increases bladder permeability in ovariectomized female rats

Aqueous Garlic Extract Inhibits Protamine Sulfate-Induced Bladder Damage

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