Early diagnosis of fetal bladder outlet obstruction

Prenatal ultrasonography has facilitated early diagnosis of in utero bladder outlet obstruction. This represents one of the earliest diagnoses of prune-belly syndrome and sheds light on the natural history of the bladder outlet obstruction in the fetus.     

Bladder development following bladder outlet obstruction in fetal lambs: optimal timing of fetal therapy

Background

Lower urinary tract obstruction causes both renal failure and bladder dysfunction after birth. This study examined the early bladder wall changes after creating an obstructive uropathy focusing on bladder wall thickness and muscle integrity.

Methods

We created obstructive uropathy in fetal lambs at 60 days' gestation, ligating the urethra and urachus. The fetuses (n = 28) were delivered at 48 hours and 3, 4, 5, 7, and 14 days after obstruction and at term (145 days' gestation). Sham-operated lambs were used as controls (n = 20). Histology samples were stained using α-smooth muscle actin) immunohistochemistry and also hematoxylin-eosin, Masson trichrome, and colloidal Fe stain.

Results

The bladder wall initially expanded and stretched. By day 4, the bladder wall became thicker. Histologically, the bladder in obstructed lambs demonstrated a prominent submucosal fibrotic change by 7 days. The mean bladder wall thickness at 14 days after obstruction was thicker than controls, and fibrosis was prominent.

Conclusion

The initial changes in the bladder wall were expansion of the muscle component followed by fibrosis. The bladder wall thickness dramatically increased 4 to 7 days after obstruction. We conclude that shunting operations to preserve bladder function may be needed earlier than expected.     

膀胱出口梗阻大鼠膀胱过度活动的研究

目的:建立膀胱出口梗阻大鼠模型,诱发逼尿肌不稳定(DI),研究膀胱出口梗阻伴发膀胱过度活动的病理生理学特征。方法:选择38只成年SD雌性大鼠,随机分为模型组和对照组,结扎膀胱颈部建立膀胱出口梗阻模型。建模后3、6、9、12周采用BL-410生物机能实验系统测定膀胱压,以充盈期出现DI作为膀胱过度活动存在的标准,记录并计算DI阳性率和频率、最大排尿压(MVP)、最大膀胱容量(MCC)、膀胱顺应性(BC)和剩余尿量(PVR)。用光镜观察建模不同时期膀胱组织的病理学改变。结果:模型组大鼠3、6、9、12周DI阳性率分别为37.50%、75.00%、75.00%、62.50%。MVP、MCC、BC、PVR和DI频率较对照组增高(P<0.01),第9周大鼠PVR、MVP、MCC高于第3、6和12周。不同时期病理学改变呈现出膀胱容量增加、肌层逐渐增厚和纤维化的过程。结论:膀胱出口梗阻与逼尿肌不稳定的发生具有潜在的相关性,其病理学改变和尿流动力学参数反映了膀胱的病理生理学特点。     

The response of fetal sheep bladder tissue to partial outlet obstruction

PURPOSE: We characterized the response of fetal ovine bladder strips to stimulated contraction and relaxation, and compared this response to that of strips from the pregnant mother and those obtained after a short duration of fetal bladder outlet obstruction. MATERIALS AND METHODS: Sham surgery or bladder obstruction was performed in fetal sheep at 90 days of gestation (term 147 days). Bladder tissue was obtained 3 and 5 days later. Isolated strips of full-thickness bladders from fetuses and pregnant females were mounted individually in Tyrode's solution containing glucose. The strips were subjected to electrical field stimulation. Alternate strips were stimulated by adding carbachol, adenosine triphosphate and KCl. Each strip stimulated by carbachol also underwent field stimulation in the presence of carbachol. Relaxation was also tested using isoproterenol and nitroprusside. RESULTS: The response of isolated strips to field stimulation showed phasic contraction or biphasic response, consisting of initial phasic contraction followed by phasic relaxation and a return to control tension after the end of stimulation. In fetal bladder strips field stimulation at all frequencies after carbachol stimulation produced phasic relaxation or a biphasic response with an initial relaxation phase followed by phasic contraction. This field stimulated relaxant response was not present in adult female bladder strips. In addition, field stimulation stimulated relaxation was completely eliminated by pretreatment with N-nitro-L-arginine-methyl ester, indicating that relaxation was nitric oxide mediated. The fetal responses to all forms of stimulation and relaxation were significantly greater than those of pregnant females. After 5 days or greater of obstruction the responses to field stimulation were reduced significantly. In contrast, there were no significant differences in contractile responses to adenosine triphosphate, carbachol or KCl, or the relaxant response to field stimulation after obstruction. However, there was a significant reduction in relaxant responses to isoproterenol and nitroprusside. CONCLUSIONS: In mid gestation sheep fetus contractile responses to field stimulation, adenosine triphosphate, carbachol and isoproterenol are well developed. The fetal ovine bladder shows a strong neuronal nitric oxide response that is not present in the pregnant mother and is maintained after short-term obstruction.     

Diagnosing bladder outlet obstruction in women

PURPOSE: There are no universally accepted urodynamic criteria for diagnosing female bladder outlet obstruction. When accepted criteria for men are applied to women, the diagnosis of obstruction may often be missed, which is most likely due to differences in voiding dynamics. We propose video urodynamic criteria for diagnosing obstruction in women, and describe the urodynamic findings in those with and without obstruction. MATERIALS AND METHODS: We reviewed the charts of 331 women who underwent multichannel video urodynamics for nonneurogenic voiding dysfunction. Of these women 261 (mean age 55.8 years) had evaluable voiding pressure flow studies with simultaneous video fluoroscopy of the bladder outlet during voiding. At video urodynamics cases were classified as obstructed if there was radiographic evidence of obstruction between the bladder neck and distal urethra in the presence of a sustained detrusor contraction. Strict pressure flow criteria were not used. Maximum flow rate, detrusor pressure at maximum flow rate, post-void residual, bladder capacity and the incidence of detrusor instability were compared between obstructed and unobstructed cases. RESULTS: A total of 76 women met the criteria for obstruction (mean age 57.5 years), while 184 (mean age 55) did not. Causes of obstruction were dysfunctional voiding in 25 cases, cystocele in 21, primary bladder neck obstruction in 12, iatrogenic from incontinence surgery in 11, urethral stricture in 3, uterine prolapse in 2, urethral diverticulum in 1 and rectocele in 1. Obstructed cases had lower mean maximum flow rate (9 versus 20.2 ml. per second, p <0.0001), higher mean detrusor pressure at maximum flow rate (42.8 versus 22.1 cm. water, p <0.0001) and higher mean post-void residual (157 versus 33 ml., p <0.0001). There was no difference in bladder capacity (381 versus 347 ml.) or incidence of detrusor instability (45 versus 41%). CONCLUSIONS: Using the proposed video urodynamic criteria obstructed cases had significantly higher voiding pressures, lower flow rates and higher post-void residual than unobstructed cases, as expected. However, absolute values, especially for voiding pressure, are not as dramatic in women as in men. Pressure flow studies alone may fail to diagnose obstruction but simultaneous imaging of the bladder outlet during voiding greatly facilitates diagnosis.     

Detrusor instability and bladder outlet obstruction

Detrusor instability is found in a high percentage of children with voiding disorders and in elderly patients both with and without bladder outlet obstruction. An assumption that outlet obstruction leads to detrusor instability has arisen largely from the findings that prostatectomy results in a marked reduction in the incidence of instability. However, studies have shown that the incidence of instability is related to age both by virtue of a decreasing incidence in childhood and an increasing incidence in later life. In later life the increase reflects advancing age and is not related to the severity of any coexisting outlet obstruction. The reduction in instability following prostatectomy may be due to an interruption of sensory afferent impulses due to resection of prostatic, urethral, and bladder neck nerve tissues. In children, instability is likely to represent delayed maturation of cerebral control over the micturition reflex, or to be due to neurological disease such as meningomyelocele. More data are required for all groups of patients, both children and adults, to determine the influence of the relief of obstruction on the incidence of instability. Furthermore, additional data are required on the incidences of instability and obstruction in the “normal” population.     

Partial bladder outlet obstruction induces urethral smooth muscle hypertrophy and decreased force generation

PURPOSE: PBOO leads to increased urinary frequency, decreased void volume, hypertrophy of the detrusor SM, and alterations in contractile and regulatory proteins. This study was done to determine whether PBOO induced increases in urinary frequency and detrusor SM hypertrophy are associated with an alteration in the contractility and expression of myosin isoforms in urethral SM. MATERIALS AND METHODS: PBOO was surgically induced in male New Zealand White rabbits, and sham operated rabbits served as controls. After surgery, rabbits were kept 12 days, and prior to sacrifice, urine output and voiding frequency were monitored by keeping the animals in metabolic cages for 24 hours. Animals with increased urinary frequency (mean +/- SEM 43 +/- 12 voids per 24 hours) and sham operated rabbits (6 +/- 3 voids per 24 hours) were used for this study. Morphology of the urethra was studied using light and immunofluorescence microscopy. The expression of myosin isoforms was analyzed at the mRNA and protein levels by RT-PCR and Western blotting. RESULTS: The urethral wall and SM of PBOO rabbits showed hypertrophy. The force produced by the longitudinal muscle strips of PBOO animals in response to phenylephrine, KCl, or electrical field stimulation was decreased 50%, 37% and 40%, respectively. Immunofluorescence microscopy revealed a decrease in nerve density. RT-PCR and Western blotting showed a decrease in the expression of myosin isoform SM-B with a concomitant increase in SM-A at the mRNA and protein levels. CONCLUSIONS: Our data show hypertrophy of the urethral wall and SM, and alterations in contraction, innervation, and myosin isoforms in PBOO induced detrusor hypertrophy.     

Partial outlet obstruction induces chronic distension and increased stiffness of rat urinary bladder

In order to identify the passive properties of the bladder during filling, we measured cystometrograms (CMGs) of rat urinary bladders that had been outlet obstructed for 6 weeks and age-matched controls in conscious, unrestrained animals and in fully relaxed whole bladders in an organ bath. In the organ bath, each bladder was allowed to empty passively at zero transmural pressure. The volume remaining was labelled zero pressure volume (ZPV) and was used as the reference volume to normalize contained volume, deriving wall stretch. Increased ZPV implies that the bladder contains more urine at low stresses and therefore is more distended. In awake animals, the obstructed bladder CMGs showed spontaneous contractions. The pressures between contractions were similar to those in CMGs performed in the organ bath, suggesting that passive properties determine the minimum pressures during filling in vivo. The ZPV of the obstructed and control bladders was 1.07 ± 0.12 ml and 0.07 ± 0.01 ml, respectively. The differences were significant (P < 0.01). The ZPV correlated with bladder weight and thus with degree of hypertrophy. Under conditions when weight cannot be determined, e.g., clinically, ZPV may provide a useful measure of the degree of chronic distension and bladder hypertrophy. The pressure-volume curves of the obstructed bladder CMGs in vitro varied between preparations. However, when pressure-volume was converted to stress-stretch using the law of Laplace, the obstructed bladders were all significantly stiffer than the controls. We confirmed this result by step-stretching relaxed bladder strips. The obstructed bladder strips again demonstrated stiffer stress-stretch curves than the controls. © Wiley-Liss, Inc.     

Detrusor pressure in bladder outlet obstruction.

Synchronous urinary flow and pressure studies were done on 51 male adults consiting of 12 normal subjects and 39 patients with varying degrees of bladder outlet obstruction due to benign prostatic hypertrophy. Mean maximum detrusor pressure levels of 50 mm. Hg and above were found to be indicative of bladder outlet obstruction. Elevated mean maximum detrusor pressure fell preoperatively within normal limits after prostatecomy. Chronic retention of urine was not associated with poor contraction of the detrusor muscle. Clinical findings of obstruction were shown to be inadequate for estimation of maximum detrusor pressure. Recording the detrusor pressure was found to be a better urodynamic test for bladder outlet obstruction than recording the urinary flow rate. Recording urinary flow is, however, a simple test and should remain a screening test for impaired drainage of the bladder outlet.     

Partial outlet obstruction of the rat bladder induces a stimulatory response on proliferation of the bladder smooth muscle cells

Outlet obstruction of the ratbladder induces hypertrophy/hyperplasiacharacterized by increases in bladder mass,smooth muscle content, and collagen deposition.In order to understand the mechanism of theoutlet obstruction-induced hypertrophy andhyperplasia, we first determined the temporalpattern of changes in bladder mass afterinducing the outlet obstruction. Histologicalanalysis revealed that the smooth muscle cellswith hypertrophy and hyperplasia, fibroblastsand connective tissue were increased in atime-dependent manner, corresponding to thetemporal pattern observed in the changes inbladder mass, although the phase of changes inthese tissue components was somewhat different.In order to further determine whether anyproliferation-stimulatory factors were releasedfrom the bladder with obstruction incorrespondence with increased bladder mass,soluble fractions were prepared from thebladders with outlet obstruction for 3–30weeks, and their effects on proliferation ofsmooth muscle cells were examined. The solublefractions prepared from the bladders at 3 to 14weeks after obstruction slightly butsignificantly facilitated the proliferation ofcultured smooth muscle cells, while the solublefractions released after 20 weeks rathersuppressed the proliferation. These resultssuggest that the initial increase in bladdermass might be in part due to the facilitatedproliferation of smooth muscle cells of thebladder body induced by growth factors releasedinto the soluble fractions, and thathypertrophy might then play a role in theincreased bladder mass at later phases.     

大鼠膀胱出口梗阻致膀胱重构的形态结构研究

目的观察大鼠膀胱出口部分梗阻不同时期的膀胱逼尿肌细胞增生、凋亡及间质中胶原纤维的变化情况。方法 Wistar大鼠40只,采用经会阴途径球部尿道部分结扎的方法建立膀胱出口部分梗阻模型,随机分为假手术组10只,梗阻2周组15只,梗阻4周组15只。采用免疫组化方法分析增殖细胞核抗原(PCNA)表达情况;通过末端转移酶标记(TUNEL)法测逼尿肌细胞凋亡指数;运用VG染色分析胶原纤维占膀胱逼尿肌面积比例变化情况。结果假手术组、梗阻2周组和梗阻4周组PCNA阳性表达率分别为(17.19±1.37)%、(50.74±3.15)%、(33.58±2.80)%,梗阻组之间差异有统计学意义(P0.05),梗阻组与假手术组之间差异有统计学意义(P0.05)。假手术组、梗阻2周组和梗阻4周组逼尿肌细胞凋亡指数分别为(20.22±1.70)%、(33.90±1.86)%、(51.18±3.30)%,梗阻组之间差异有统计学意义(P0.05),梗阻组与假手术组之间差异有统计学意义(P0.05)。假手术组、梗阻2周组和梗阻4周组胶原纤维占膀胱逼尿肌面积比例分别为(7.07±0.67)%、(13.19±1.50)%、(22.98±2.89)%,梗阻组之间差异有统计学意义(P0.01),梗阻组与假手术组之间差异有统计学意义(P0.01)。结论不同时期大鼠膀胱出口梗阻的膀胱逼尿肌形态结构的变化,可能是膀胱逼尿肌细胞增生、凋亡以及间质中胶原纤维占膀胱逼尿肌比例变化的综合作用结果。     

Ultrasound diagnosis of bladder outlet obstruction in rabbits

One of the primary characteristics of partial outlet obstruction secondary to BPH is an increase in bladder mass commonly referred to as bladder hypertrophy. This condition has been simulated in rabbits by the partial ligation of the catheterized urethra. Ultrasonography has been utilized in both adult and pediatric urology to visualize the bladder and diagnose specific bladder disorders. The aim of the present study is to determine if ultrasonography can visualize bladder wall hypertrophy induced by obstruction. Partial outlet obstructions were created in NZW rabbits using standard methodologies, and then 5 to 7 days later, sonography was performed. The films were read by both the principal investigator and blinded investigators instructed to determine bladder wall thickness and from this predict the bladder weight. Then results were correlated with cystometrograms (CMGs) and whole bladder weights. Both the principal investigator and the blinded investigators were consistently able to distinguish obstructed from control bladders based solely on sonographic depictions of relative bladder wall thickness. In addition, the investigators were able to distinguish between low (control), medium, and high bladder weights based on sonography. The accuracy of predicting the bladder weights increased when cystosonograms were correlated with CMC studies. Thus, the degree of bladder hypertrophy can be accurately estimated by the combination of cmg and ultrasonography. © 1994 Wiley-Liss, Inc.     

排尿期尿道压力测定在膀胱出口梗阻疾病诊断中的应用

目的　研究排尿期尿道压力测定 (MUPP)在膀胱出口梗阻 (BOO)疾病诊断中的应用。方法　下尿路梗阻患者 4 5例 ,其中良性前列腺增生 (BPH) 38例 ,前尿道狭窄 3例 ,女性尿道狭窄 4例。对照组为健康志愿者 4例。按常规方法行压力 流率测定 ,静态尿道压力测定 (UPP)及MUPP。以压力下降梯度计算梗阻程度。数据分析采用t检验。研究不同疾病梗阻患者尿道压力下降点及下降梯度 ,MUPP对梗阻部位的诊断价值 ,MUPP与压力 流率研究对可疑梗阻诊断的比较 ,MUPP与压力 流率研究判断梗阻程度的比较。　结果　对照组 2例男性 ,外括约肌以上尿道内压与膀胱内压力相等 ,尿道压在外括约肌处快速下降 ;2例女性 ,膀胱压与全部尿道压几乎相等 ,尿道末端 1cm处尿道压下降。 38例BPH患者最大排尿压增高 ,平均为 (99.33± 4 1.0 9)cmH2 O(1cmH2 O =0 .0 98kPa) ,尿道压力在膀胱颈或前列腺尖部下降。 3例前尿道狭窄患者后尿道近端压力与膀胱压相等 ,球部及远端尿道压力下降。 4例女性远端尿道狭窄患者尿道压力在狭窄远端区域下降。BPH、前尿道狭窄、女性远端尿道狭窄平均MUPP压力下降梯度分别为 (71.6 3± 37.4 1)cmH2 O、(43.5 1± 15 .71)cmH2 O、(41.4 8± 17.34)cmH2 O ,与正常对照组的 (2 4 .2 5± 2 .99)cmH2 O相比 ,差别有