Is the urothelium intelligent?

Abstract

The urothelium separates the urinary tract lumen from underlying tissues of the tract wall. Previously considered as merely an effective barrier between these two compartments it is now recognized as a more active tissue that senses and transduces information about physical and chemical conditions within the urinary tract, such as luminal pressure, urine composition, etc. To understand this sensory function it is useful to consider the urothelium and suburothelium as a functional unit; containing uroepithelial cells, afferent and efferent nerve fibers and suburothelial interstitial cells. This structure responds to alterations in its external environment through the release of diffusible agents, such as ATP and acetylcholine, and eventually modulates the activity of afferent nerves and underlying smooth muscles. This review considers different stresses the urothelium/suburothelium responds to; the particular chemicals released; the cellular receptors that are consequently affected; and how nerve and muscle function is modulated. Brief consideration is also to regional differences in the urothelium/suburothelium along the urinary tract. The importance of different pathways in relaying sensory information in the normal urinary tract, or whether they are significant only in pathological conditions is also discussed. An operational definition of intelligence is used, whereby a system (urothelium/suburothelium) responds to external changes, to maximize the possibility of the urinary tract achieving its normal function. If so, the urothelium can be regarded as intelligent. The advantage of this approach is that input–output functions can be mathematically formulated, and the importance of different components contributing to abnormal urinary tract function can be calculated.

Intakes of Vitamins and Minerals in Relation to Urinary Incontinence, Voiding, and Storage Symptoms in Women: A Cross-Sectional Analysis from the Boston Area Community Health Survey

“…Highly acidic urine, such as could result from high-dose vitamin C [24], plausibly could affect the urothelium and contribute to LUTS. The urothelium responds to changes in its environment, including urine composition and pH, by releasing diffusible agents and modulating the activity of afferent nerves and underlying smooth muscles [25]. A study of the effects of urinary pH on bladder sensitivity in asymptomatic women found that increased urine acidity led to increased micturition desire [26].…”

Idiopathic Cystitis in Domestic Cats—Beyond the Lower Urinary Tract

“…The urothelium is composed of a basal cell layer attached to a basement membrane, an intermediate layer, and a superficial apical layer 66 . Although healthy urothelium maintains a tight barrier to ion and solute flux, factors such as altered pH or electrolyte concentrations, mechanical, chemical, or neurally mediated stimulation, and infectious agents all can impair the integrity of the barrier 67 …”

Sophisticated models and methods for studying neurogenic bladder dysfunction

“…It is hypothesized that there is communication between the different cell layers in the bladder wall during filling, with transduction of signals from the urothelium to interstitial cells, afferent nerves, and smooth muscle 17. Alterations in this signaling pathway are believed to be an underlying cause of detrusor overactivity.…”