Evidence for Bladder Urothelial Pathophysiology in Functional Bladder Disorders

Abstract

Understanding of the role of urothelium in regulating bladder function is continuing to evolve. While the urothelium is thought to function primarily as a barrier for preventing injurious substances and microorganisms from gaining access to bladder stroma and upper urinary tract, studies indicate it may also function in cell signaling events relating to voiding function. This review highlights urothelial abnormalities in bladder pain syndrome/interstitial cystitis (BPS/IC), feline interstitial cystitis (FIC), and nonneurogenic idiopathic overactive bladder (OAB). These bladder conditions are typified by lower urinary tract symptoms including urinary frequency, urgency, urgency incontinence, nocturia, and bladder discomfort or pain. Urothelial tissues and cells from affected clinical subjects and asymptomatic controls have been compared for expression of proteins and mRNA. Animal models have also been used to probe urothelial responses to injuries of the urothelium, urethra, or central nervous system, and transgenic techniques are being used to test specific urothelial abnormalities on bladder function. BPS/IC, FIC, and OAB appear to share some common pathophysiology including increased purinergic, TRPV1, and muscarinic signaling, increased urothelial permeability, and aberrant urothelial differentiation. One challenge is to determine which of several abnormally regulated signaling pathways is most important for mediating bladder dysfunction in these syndromes, with a goal of treating these conditions by targeting specific pathophysiology.

Diagnosticando a cistite idiopática felina: Revisão

“…A forma ulcerativa é evidenciada pela presença das chamadas úlceras de Hunner (Dibartola, 2015). O tipo II parece ser mais inflamatório, enquanto o tipo I pode estar associado às anormalidades neuroendócrinas, sugerindo que a inflamação pode ocorrer "em resposta a" em vez de ser "uma causa de" dano ao urotélio da bexiga (Keay et al, 2014). Foi demonstrado em pesquisa na bexiga de gatos com CIF crônica, que alterações histológicas são geralmente inespecíficas e podem incluir um urotélio intacto ou danificado com edema submucoso, dilatação de vasos sanguíneos submucosos com neutrófilos marginais, hemorragia submucosa e, por vezes, aumento da densidade de mastócitos (Buffington et al, 1997).…”

“…Pereira et al, (2004) encontraram sulfato de condroitina no plasma de gatos com síndrome urológica felina (SUF), levando-os a concluir que a diminuição da concentração de condroitina encontrada na urina poderia resultar da eabsorção por um urotelio mais permeável. Essas alterações na barreira urotelial também podem permitir que a água, a ureia e as substâncias nocivas presentes na urina passem para o tecido subjacente (camadas neurais e outras), resultando em STUI (Keay et al, 2014).…”

“…A NE circulante no organismo do gato com CIF, por sua vez, apresenta-se aumentada tanto em estados de repouso quanto excitatórios (Anjos, 2014). O que poderia explicar altos níveis contínuos de NE seriam eventos de stress, inflamação e dor igualmente contínuos, ativando o sistema nervoso simpático (SNS) e seus mediadores, tal como o fator liberador de corticotrofina (CRF) (Keay et al, 2014) e a enzima tirosina-hidroxilase (TH) (Sands et al, 2000).…”

Transient Receptor Potential Vanilloid 1 in animal tissues: An overview to highlight similarities and differences with human species

“…The research group of Keay in 2014 [32] , studied the role of urothelium in regulating bladder function during pathological conditions such as bladder pain syndrome/interstitial cystitis (BPS/IC), FIC and non-neurogenic idiopathic overactive bladder (OAB). All the mentioned pathologies are characterized by symptoms concerning lower urinary tract, such as urgency, incontinence, nocturia, and pain.…”

“…All the mentioned pathologies are characterized by symptoms concerning lower urinary tract, such as urgency, incontinence, nocturia, and pain. Keay and co-workers [32] compared symptomatic and asymptomatic humans and cats, discovering that all symptomatic patients share some common features, including increased purinergic, TRPV1, and muscarinic signalling, increased urothelial permeability, and aberrant urothelial differentiation.…”