Bladder functional disorders are common health problems; however, their pathologies are poorly understood. Adenosine triphosphate (ATP) released from the urothelium has been suggested to have an essential role in the micturition reflex, and its involvement in bladder functional disorders has been intensively investigated. Here, we review the latest advances in research on urothelial ATP signaling.
We reviewed research articles on the role of the urothelium and urothelial ATP release in bladder function.
Mice lacking purinergic receptors have been reported to exhibit marked bladder hyporeflexia. Based on this observation, it was commonly believed, according to the widely held ATP urothelial signaling theory, that stretch-induced urothelial ATP release mediates the sensation of bladder filling via purinergic receptors. However, recent studies employing novel experimental methods and approaches have demonstrated that there are no significant differences in bladder function between wild-type and purinergic receptor knockout mice under physiological conditions. Nonetheless, under pathological conditions, inhibition of purinergic receptors has been shown to improve bladder hyperactivity. Moreover, enhanced urothelial ATP release has been reported in patients with bladder functional disorders.
Recently, conflicting evidence has led us to question the role of urothelial ATP signaling in normal micturition reflex. In contrast, under pathological conditions, it seems likely that enhanced urothelial ATP signaling mediates bladder hyperactivity. These recent findings suggest that the urothelial ATP signaling pathway is a potential therapeutic target for bladder functional disorders.
Abstract AIMS: This is a pilot study to evaluate the feasibility of using diagnostic cardiac electrophysiology catheters for recording intrinsic urinary bladder electrical activity and for electrical pacing capture of bladder tissue. METHODS: During cystoscopy, a curved quadripolar catheter was introduced and contact was made with the right and left halves of the dome and trigone in adult female patients undergoing cystoscopy. Electrical activity was recorded, using a commercially available cardiac electrophysiologic recording system, before and during pacing at 0.5-3.0 Hz. RESULTS: Apparent spontaneous electrical depolarizations were detected in both the trigone and the dome. The amplitude of these depolarizations was in the microVolt range. During pacing, local electrical capture was noted in the trigone, but not in the dome. CONCLUSIONS: Spontaneous low-amplitude electrical activity was detected in the bladder through the use of commercially available cardiac electrophysiology equipment. While these low-level signals could represent noise, the voltage, and morphology resemble detrusor muscle action potentials previously seen in animal studies. Pacing induced local electrical capture in the trigone but not the dome.
PMID: 27494644 [PubMed - as supplied by publisher]
Hollander, J.B. Int Urol Nephrol (2016). doi:10.1007/s11255-016-1374-0
Urology - Book review
There is a great need in the world for skilled urologic practitioners. Urology physician extenders such as nurse practitioners, physician assistants and specialty trained medical assistants will be needed more and more in order to deliver timely and appropriate care to urologic patients. The office practice manual “The Nurse Practitioner in Urology” is now available and has the potential to become a main resource for office practice in urology. Written by urology nurse practitioners with over 32 years of urologic experience between them, the book serves as a guide for physician extenders in order to provide expert high quality cost effective care for adult urology patients. The book to me is so well written and practical that it may serve as a resource for office urologists themselves. The chapter highlights pertinent pathophysiology, assessment and diagnostics specific to GU conditions and promotes advanced critical thinking for physician extenders specializing in urology. The chapters are written with clinical pearls and practical resources that may be of value not only to physician extenders, but clinicians and patients themselves. In addition to standard outpatient management of both benign and malignant urological conditions, there are chapters on transitioning pediatric urology patients to adult environments, men’s health including low testosterone, erectile dysfunction and infertility, and newer concepts with regard to urinary retention and underactive bladder. The book emphasizes evidence based medicine and the resources necessary to practice in that fashion. The book is user friendly and easy to navigate. “The Nurse Practitioner in Urology” will be a valued asset to all mid-level providers, physician extenders and specialists in the office based practice in urology. I suspect it will be a valued asset to busy state-of-the-art urological offices.
Abstract PURPOSE: To assess the prevalence, awareness, and quality of life (QOL) impact of symptoms suggestive of underactive bladder (UAB) in the USA. METHODS: A thirteen-item paper survey was mailed to 25,000 individuals 60 years or older living in the USA. It aimed to collect information relating to demographics, familiarity with UAB, patient urinary symptoms, and QOL concerns. RESULTS: Nine hundred and seventy-seven survey participants were stratified into four groups based on the number of UAB symptoms (straining, retention, and difficulty emptying) present: zero, one, two, and three. As the number of reported UAB symptoms increased, there was an increase prevalence in nocturia, urge, and urinary frequency (p < 0.0001). Increased UAB symptoms were associated with an increased prevalence of concerns related to urgency, urge incontinence, nocturia, and overall urinary status (p < 0.0001). Urology visits were most common in individuals who reported the most UAB symptoms (p < 0.0001); however, there was no difference among groups with regard to UAB awareness. Women were less likely to report any UAB symptoms (p < 0.0001), symptoms of urge (p = 0.001), retention (p = 0.002), difficulty emptying their bladder (p < 0.0001), a history of catheter use for retention (P = 0.002), and urology visits in the past 3 years (p < 0.0001). This study is limited in its inability to differentiate UAB from disorders that may mimic UAB clinically, based on the survey questions asked. CONCLUSIONS: Underactive bladder symptoms are common and can have a significant impact on ones QOL, although awareness is still lacking among potentially affected individuals. More must be done to allow one to better differentiate between UAB and conditions that are clinically similar.
PMID: 27473156 [PubMed - as supplied by publisher]
Functional and Molecular Characterization of Hyposensitive Underactive Bladder Tissue and Urine in Streptozotocin-Induced Diabetic Rat.
PLoS One. 2014;9(7):e102644
Authors: Nirmal J, Tyagi P, Chuang YC, Lee WC, Yoshimura N, Huang CC, Rajaganapathy B, Chancellor MB
Abstract BACKGROUND: The functional and molecular alterations of nerve growth factor (NGF) and Prostaglandin E2 (PGE2) and its receptors were studied in bladder and urine in streptozotocin (STZ)-induced diabetic rats. METHODOLOGY/PRINCIPAL FINDINGS: Diabetes mellitus was induced with a single dose of 45 mg/kg STZ Intraperitoneally (i.p) in female Sprague-Dawley rats. Continuous cystometrogram were performed on control rats and STZ treated rats at week 4 or 12 under urethane anesthesia. Bladder was then harvested for histology, expression of EP receptors and NGF by western blotting, PGE2 levels by ELISA, and detection of apoptosis by TUNEL staining. In addition, 4-hr urine was collected from all groups for urine levels of PGE2, and NGF assay. DM induced progressive increase of bladder weight, urine production, intercontraction interval (ICI) and residual urine in a time dependent fashion. Upregulation of Prostaglandin E receptor (EP)1 and EP3 receptors and downregulation of NGF expression, increase in urine NGF and decrease levels of urine PGE2 at week 12 was observed. The decrease in ICI by intravesical instillation of PGE2 was by 51% in control rats and 31.4% in DM group at week 12. CONCLUSIONS/SIGNIFICANCE: DM induced hyposensitive underactive bladder which is characterized by increased inflammatory reaction, apoptosis, urine NGF levels, upregulation of EP1 and EP3 receptors and decreased bladder NGF and urine PGE2. The data suggest that EP3 receptor are potential targets in the treatment of diabetes induced underactive bladder.
PMID: 25050870 [PubMed - as supplied by publisher]
Differences in urodynamic variables for vesicoureteral reflux depending on the neurogenic bladder type.
Ann Rehabil Med. 2014 Jun;38(3):347-52
Authors: Lee JS, Koo BI, Shin MJ, Chang JH, Kim SY, Ko HY
Abstract OBJECTIVE: To compare the urodynamic study variables at the onset of vesicoureteral reflux (VUR) between the overactive and underactive bladders in patients with spinal cord injury who presented with VUR. METHODS: A total of 28 (13 cases of detrusor overactivity and 15 detrusor underactivity) men were enrolled. We compared the urodynamic variables between the two groups; detrusor pressure and bladder compliance, the infused volume at the onset of VUR measured on a voiding cystourethrography and cystometric capacity, maximum detrusor pressure, and bladder compliance during filling cystometry were recorded. RESULTS: At the onset of VUR, the bladder volume and compliance, except for the detrusor pressure, showed a significant difference between the two groups. The detrusor pressure, bladder volume, and bladder compliance relative to the cystometric capacity showed a significant difference between the two groups. The detrusor pressure, bladder volume, and bladder compliance at the onset of VUR relative to the cystometric bladder capacity did not show any significant difference between the two groups. CONCLUSION: There were differences in some variables at the onset of VUR depending on the type of neurogenic bladder. The VUR occurred at a lower capacity in neurogenic bladder with detrusor overactivity than in neurogenic bladder with detrusor underactivity at the same pressure. VUR occurred at a lower intravesical pressure compared to that known as the critical detrusor pressure (≥40 cm H2O) required for the development of VUR. The results of our study demonstrate that the detrusor pressure should be maintained lower than the well known effective critical detrusor pressure for the prevention and treatment of VUR.