Bladder under stress: Pathological and adaptive shifts in channel expression

Re: Karl H. Pang, Riccardo Campi, Salvador Arlandis, et al. Diagnostic Tests for Female Bladder Outlet Obstruction: A Systematic Review from the European Association of Urology Non-neurogenic Female LUTS Guidelines Panel. Eur Urol Focus 2022;8:1015–30

Urothelial dysfunction and sensory protein expressions in patients with urological or systemic diseases and hypersensitive bladder

Changes in the Function and Expression of T-Type and N-Type Calcium Channels in the Rat Bladder after Bladder Outlet Obstruction

Vector Flow Visualization of Urinary Flow Dynamics in a Bladder Outlet Obstruction Model

IntroductionAssessment of bladder wall thickness by ultrasound is influenced by bladder distension and body weight, complicating interpretation. In the author’s experience, cranial or cranio-ventral bladder wall thickening is commonly observed in dogs without lower urinary tract disease. One of our main hypotheses is that this thickening reflects physiological mucosal folding, which becomes more pronounced as bladder distension decreases. However, bladder thickening remains poorly documented in healthy dogs. This study aimed to investigate the prevalence and characteristics of bladder wall thickening in dogs without lower urinary tract disease.MethodsMedical data of 136 dogs without lower urinary tract disease signs, undergoing abdominal ultrasound and urinalysis, were retrospectively reviewed. Ultrasound data included bladder wall thickening presence and localization (cranial, ventral, cranio-ventral, …, generalized), aspect of the luminal surface (smooth-irregular) and the urine, and bladder distension (empty, mild, moderate, severe). A wall thickness ratio (maximum/minimum thickness) was calculated in cases of asymmetrical thickness. Multivariate logistic regression (p < 0.05) assessed associations between bladder wall thickening and other medical and ultrasound data.ResultsBladder wall thickening was observed in 42.6% of cases, predominantly in the cranio-ventral region (22.1%), followed by the cranial (11%), generalized (8%), and ventral (5%) regions. Thickening was more frequent in mildly (29.4%) and moderately (10.3%) distended bladders. Significant associations were found between thickening and age (OR = 1.16), gastrointestinal (OR = 5.49), and renal diseases (OR = 5.57). Sterilized dogs were less likely to exhibit cranio-ventral thickening (OR = 0.36). The median thickness ratio was not statistically significant across bladder sizes (p = 0.82): 2.0 for mildly, 1.95 for moderately, and 1.9 for severely distended bladder.ConclusionThese findings suggest that mild cranio-ventral/cranial bladder thickening is common in dogs without lower urinary tract disease with a median thickness ratio ≤ 2.0 and should not be confound with cystitis.

The use of onabotulinumtoxinA (BoNT-A) for the treatment of lower urinary tract diseases (LUTD) has increased markedly in recent years. The indications for BoNT-A treatment of LUTD now include neurogenic or idiopathic detrusor overactivity, interstitial cystitis/bladder pain syndrome and voiding dysfunction. The mechanisms of BoNT-A action on LUTDs affect many different aspects. Traditionally, the effects of BoNT-A were believed to be attributable to inhibition of acetylcholine release from the presynaptic efferent nerves at the neuromuscular junctions in the detrusor or urethral sphincter. BoNT-A injection in the bladder also regulated sensory nerve function by blocking neurotransmitter release and reducing receptor expression in the urothelium. In addition, recent studies revealed an anti-inflammatory effect for BoNT-A. Substance P and nerve growth factor in the urine and bladder tissue decreased after BoNT-A injection. Mast cell activation in the bladder also decreased. BoNT-A-induced improvement of urothelium function plays an important mitigating role in bladder dysfunction. Vascular endothelial growth factor expression in urothelium decreased after BoNT-A injection, as did apoptosis. Studies also revealed increased apoptosis in the prostate after BoNT-A injection. Although BoNT-A injection has been widely used to treat different LUTDs refractory to conventional treatment, currently, onabotulinumtoxinA has been proven effective only on urinary incontinence due to IDO and NDO in several large-scale clinical trials. The effects of onabotulinumtoxinA on other LUTDs such as interstitial cystitis, benign prostatic hyperplasia, dysfunctional voiding or detrusor sphincter dyssynergia have not been well demonstrated.

In men, lower urinary tract symptoms (LUTS) similar to interstitial cystitis/bladder pain syndrome (IC/BPS) are difficult to diagnose, and treatment outcomes are poor. This study investigated clinical characteristics and videourodynamic study (VUDS) parameters, pathophysiology, and treatment outcomes in men with IC-like LUTS. Men with frequency, urgency, dysuria, and bladder pain initially diagnosed as IC/BPS by ESSIC criteria were assessed to rule out other lower urinary tract diseases (LUTD) by voiding diary, digitorectal examination, urinalysis, VUDS, and cystoscopic hydrodistention. Subsequent treatments for LUTD and specific treatment for IC/BPS were based on VUDS and cystoscopic findings. Clinical VUDS characteristics and treatment outcomes were compared with those of women with IC/BPS. Seventy consecutive men (median age 54.5years) were enrolled. The median maximum bladder capacity under cystoscopic hydrodistention was 650mL (IQR 495-763) and glomerulation grade was 2 (1.0-2.0). The patients had moderate anxiety and depression severity; 49% had improved treatment outcomes. On VUDS, 42 (60%) patients had variable LUTD, including detrusor overactivity (n = 14), bladder neck dysfunction (n = 15), dysfunctional voiding (n = 3), and poor relaxation of the external sphincter (n = 24); also, 22 (31.4%) had a previous bladder outlet procedure. The self-reported treatment outcome was significantly better for patients with vs. without LUTD (p = 0.014). Men with IC-like LUTS diagnosed as IC/BPS may have bladder outlet dysfunction as well as bladder dysfunction, causing a hypersensitive and painful bladder. The IC-like symptoms in the patients with LUTD might, in part, originated from bladder outlet dysfunction rather than the bladder alone.

Urodynamic Differences Between Dysfunctional Voiding and Primary Bladder Neck Obstruction in Women

Ultrasound Measurement of Bladder Wall Thickness in the Assessment of Voiding Dysfunction

To analyze the lower urinary tract symptoms (LUTS) and video-urodynamic characteristics of women with clinically unsuspected bladder outlet obstruction (BOO). From 1997 to 2010, a total of 1605 women with bothersome LUTS received video-urodynamic study in our unit. We reviewed the charts of 212 women diagnosed with BOO based on video-urodynamic criteria and 264 women without abnormal findings. LUTS and urodynamic parameters were compared between obstructed and unobstructed cases and among the BOO subgroups. The mean ages of the BOO (58.2 years) and control groups (58.8 years) were similar. The mean values of detrusor pressure at maximum urinary flow rate (Pdet Qmax )/maximum flow rate (Qmax ) of the BOO and control groups were 51.83 cm H2 O/10.22 mL/s versus 18.81 cm H2 O/20.52 mL/s. In the BOO group, cinefluoroscopy revealed dysfunctional voiding in 168 patients (79.2%), urethral stricture in 17 (8.0%), and bladder neck dysfunction in 27 (12.7%). Patients with dysfunctional voiding had significantly lower urethral resistance compared with the other two BOO subgroups. Combined lower urinary tract symptoms were present most often in all BOO patients (69.3%), followed by isolated storage symptoms (30.2%) and isolated voiding symptoms (0.5%). Seventy-seven patients (37.3%) had dysuria and 79 patients (36.3%) had frequency as their main symptom. Women with BOO usually have nonspecific LUTS. Dysfunctional voiding was the most common form among women with clinically unsuspected BOO, but the degree of obstruction was less severe than with primary bladder neck obstruction and urethral stricture.

2279 URODYNAMIC FINDINGS IN WOMEN WTH OBSTRUCTIVE VOIDING SYMPTOMS

Background Parkinson's disease (PD) is an extrapyramidal neurological disorder. Urinary symptoms are frequently present in patients affected by PD. Symptoms such as urgency, frequency, nocturia, and urge incontinence significantly impact the patient's quality of life. We attempted to investigate the urodynamic changes and treatment of male PD patients with voiding dysfunction by means of a review. Methods Comprehensive urodynamic examinations were performed in 141 male patients with PD associated with voiding dysfunction. Appropriate treatments were given to subgroups that were divided based on test results, and the changes in urodynamic parameters as well as the treatment efficacy were observed. Results Detrusor hyperreflexia without bladder outlet obstruction (BOO) was observed in 35 patients, who exhibited significant improvements in the international prostate symptom score (IPSS), maximum flow rate (Qmax), bladder volume at the first desire to void, post-void residual (PVR), and bladder compliance. Detrusor hyperreflexia associated with BOO was observed in 59 patients. The patients exhibited significant improvements in IPSS, Qmax, PVR, and bladder compliance. Detrusor dysfunction without BOO was observed in 19 patients, for whom the IPSS and the bladder volume at the first desire to void were improved after treatment. Detrusor dysfunction with BOO was found in 28 patients, with no significant improvement in the urodynamic parameters after the treatment. Conclusions Urodynamic examination is recommended for male Parkinson's disease patients with voiding dysfunction. Early and effective treatment can improve the bladder function and quality of life of these patients.

To assess the value of video-urodynamic study (VUD) in the identification of lower urinary tract voiding dysfunction in female. A total of 126 female patients with sign and symptoms of lower urinary tract voiding dysfunction underwent VUD from December 2008 to January 2011 in Beijing Chaoyang Hospital. The causes of voiding dysfunction were analyzed based on VUD findings. Neurogenic voiding dysfunction was found in 30 patients (23.8%), non-neurogenic voiding dysfunction was found in 96 patients (76.2%). The 72 patients suffered from recurrent urinary tract infection (57.1%) and 23 patients suffered from hydronephrosis (18.3%). Based on special characteristics of video-urodynamic study, a total of 126 patients were classified as: (1) Bladder outlet obstruction (BOO) was found in 65 patients. Of them, bladder neck obstruction in 40 patients (61.5%), their VUD showed "high pressure-low flow" obstructive curve and synchronic image showed bladder neck did not open in a funnel shape and no contrast was found in urethra. Distal urethral stricture in 22 patients (33.8%), VUD showed "high pressure-low flow" obstructive curve and synchronic image showed bladder neck open in a funnel shape, proximal urethra dilated and no contrast was found in distal urethral. Urethral sphincter obstruction in 3 patients (including detrusor-sphincter dyssynergia in 1 and sphincterismus in 2 patients), VUD showed "high pressure-low flow" obstructive curve and synchronic image showed bladder neck open in a funnel shape, sphincteric urethra did not open, proximal urethra dilated and no contrast was found in distal urethral. (2) Detrusor areflexia (DA) was found in 39 patients (2 patients with hydronephrosis), the VUD finding was: no voluntary detrusor contraction in voiding phase, and abdominal pressure voiding pattern. (3) OAB was found in 3 patients, which VUD findings was frequent involuntary detrusor contraction at storage period with or without urine leakage. (4) Low compliance bladder was found in 17 patients (13.5%), 16 patients with hydronephrosis, the VUD showed that increased bladder storage pressure with significantly decreased bladder safe capacity and compliance, appearance of the bladder as "Christmas tree", with or without ureteral reflux. (5) And stress urinary incontinence (SUI) was in 2. The main causes of female BOO may be non-neurogenic conditions or organic obstruction. VUD would offer valuable information for confirmed diagnosis of voiding dysfunction in female patients.

THE DECOMPENSATED DETRUSOR III: IMPACT OF BLADDER OUTLET OBSTRUCTION ON SARCOPLASMIC ENDOPLASMIC RETICULUM PROTEIN AND GENE EXPRESSION

Voiding dysfunction in women: How to manage it correctly