How does the urothelium affect bladder function in health and disease? ICI-RS 2011

Abstract

The urothelium is a multifunctional tissue that not only acts as a barrier between the vesical contents of the lower urinary tract and the underlying tissues but also acts as a sensory organ by transducing physical and chemical stresses to the attendant afferent nervous system and underlying smooth muscle. This review will consider the nature of the stresses that the urothelium can transduce; the transmitters that mediate the transduction process; and how lower urinary pathologies, including overactive bladder syndrome, painful bladder syndrome and bacterial infections, are associated with alterations to this sensory system. In particular, the role of muscarinic receptors and the TRPV channels system will be discussed in this context. The urothelium also influences the contractile state of detrusor smooth muscle, both through modifying its contractility and the extent of spontaneous activity; potential pathways are discussed. The potential role that the urothelium may play in bladder underactivity is introduced, as well as potential biomarkers for the condition that may cross the urothelium to the urine. Finally, consideration is given to vesical administration of therapeutic agents that influence urinary tract function and how the properties of the urothelium may determine the effectiveness of this mode of delivery.

Figure 1

A diagram of the bladder wall and some of the external factors that influence urothelial function. The mucosa consists of a true urothelium and suburothelium and is in contact with an external proteoglycan layer facing the urine. The urothelium includes an outer layer of umbrella cells facing the urine and coupled by tight junctions thus reducing the ability of solutes to penetrate the urothelium. The suburothelium contains afferent nerve fibres, blood vessels and interstitial cells and at the inner face some muscle cells. Upon exposure to external stresses the urothelium releases a number of transmitters including that may influence afferent nerve activity or diffuse to the detrusor layer and alter contractile function, these include: ATP, acetylcholine (ACh), nitric oxide (NO) and prostaglandins (PG). External factors affecting transmitter release include physical factors, such as change of transmural pressure, ΔP, or lateral or tortional strain, or changes to the chemical composition of urine or the blood.