The purpose of the lower urinary tract is to allow for low-pressure bladder filling and storage of urine without incontinence and voluntary complete expulsion of urine. This is made possible by an intricate balance of neural control, numerous neurotransmitters, subtle anatomic relations, and a variety of pharmacological and mechanical properties. This complex system can be simplified into the two phases of the micturition cycle: bladder filling with urine storage and bladder emptying or voiding.1 The focus of this chapter will be on problems that women face in regard to their ability to successfully empty their bladder, termed voiding phase dysfunction.
In the simplest terms, the micturition/voiding phase requires a detrusor contraction that is of sufficient strength and of sufficient duration to overcome the resistance of the bladder outlet. Any alterations, or combinations of alterations, that affect the strength/duration of the detrusor contraction, that increase the resistance of the outlet, or that affect the coordination of these actions, are potential causes of impaired emptying. Ineffective or incomplete emptying can be caused by a problem with the bladder (impaired or absent contractility) or a problem with the outlet (obstruction—anatomic or functional). Table 8-1 shows a list of possible physiological causes of impaired emptying based on this functional classification. One must be careful in making a clinical diagnosis of “acontractile” or “hypocontractile” bladder, as behavior during urodynamics may not mimic that of daily living. For example, if a patient normally voids yet cannot do so during a urodynamics study, she may not truly have an acontractile bladder.
Etiology of Voiding Phase Dysfunction
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Key Points
The micturition/voiding phase requires a detrusor contraction that is of sufficient strength and duration to overcome the resistance of the bladder outlet.
Ineffective or incomplete emptying can be caused by a problem with the bladder (impaired contractility) or a problem with the outlet (obstruction).
This chapter will review the pathophysiology underlying the different etiologies for common conditions causing ineffective emptying, general evaluation of voiding dysfunction, followed by treatment options for each condition.
Detrusor underactivity is defined by the International Continence Society (ICS) as a contraction of reduced strength and/or duration, resulting in prolonged emptying and/or a failure to achieve complete bladder emptying within a normal time span.2 This condition has various causes that can be divided into neuropathic, myogenic, and pharmacologic etiologies.
Neuropathic etiologies of detrusor underactivity include pathology involving lower motor neurons and decentralizations. A review of the neural innervation responsible for normal micturition will allow the clinician to determine the effect a nerve injury may have on voiding. During normal bladder emptying, a signal to void comes from the efferent output of the pelvic plexus (S2–S4). From the spinal cord, this message is sent to the bladder via the pelvic nerve. At the same time, inhibitory messages are sent through the hypogastric and pudendal pathways to allow for relaxation of the sphincter mechanism and coordination of voiding.3 Most iatrogenic pelvic nerve injuries come from injury of the pelvic plexus or pelvic nerve.
The incidence of neurologic injury from radical pelvic surgery is based mostly on older literature, and consequently may reflect older surgical techniques. For patients undergoing abdominal perineal resection, for example, rates of injury have been reported ranging between 7.5% to 70%.4 Radical hysterectomy is another commonly encountered cause for pelvic plexus/pelvic nerve injury in women. Following radical hysterectomy, the number of clinically significant lower urinary tract symptoms (LUTS) range from 8% to 80%. A minority of this dysfunction is attributed to issues with bladder contractility and a majority of symptoms are storage-related.5 Voiding phase dysfunction following radical surgery is not always permanent and some function may return. However, need for urethral catheterization immediately after radical hysterectomy was a risk factor for developing long-term (defined as two years) dysfunction in the form of elevated postvoid residual (PVR) and voiding by abdominal straining.
Long-term data following radical surgery are sparse. A retrospective study of patients referred for LUTS, or other lower urinary tract abnormalities, examined urodynamic findings at least ten years after radical hysterectomy and this study should be interpreted in light of these limitations. All patients evaluated did void with abdominal straining, and no detrusor contractions were seen.6 A large proportion of these women also had concomitant pelvic radiation. Anterior resections and proctocolectomy are other pelvic procedures that carry risk of injury to the voiding mechanism.
Spinal cord surgery is also implicated in voiding phase dysfunction. A recent retrospective review of cervical and lumbar surgeries found a urinary retention rate up to 38%. Although this study reports a higher rate of retention than other reports, gender was not a risk factor for retention. The authors did not propose a mechanism of the self-limited retention, but given that they observed no difference between cervical and lumbar procedures, they suggest that the factors leading to voiding dysfunction are not related to spinal cord or root-mediated effects.7
Other spinal pathology has been implicated in neuropathic detrusor underactivity. A study of one hundred women with urinary retention, mean age 58 years, revealed that cervical/thoracic tumors were the underlying pathology in 8%, lumbar spondylosis in 5%, posterior longitudinal ligament ossification in 5%, and cauda equina/spinal conus tumor in 5%. Multiple system atrophy was the most common underlying disease (19%) followed by multiple sclerosis (MS) (13%).8
Myogenic detrusor underactivity occurs from disorders directly or indirectly affecting the bladder muscle. Two common causes of myogenic detrusor underactivity are diabetic cystopathy, chronic obstruction and other causes of chronic bladder overdistention. Diabetic cystopathy has a historical prevalence of approximately 25% among patients on oral hypoglycemic agents and upward of 87% in patients on insulin, with most of these numbers from publications in the 1960s and 1970s.9-10 The mechanism of diabetic cystopathy is multifactorial including alterations not only in detrusor smooth muscle, but also urothelial function, and innervation.11-12 Diabetes likely contributes directly to alterations in detrusor smooth muscle dysfunction, but the effect on urothelial function and nerve function may also contribute to the clinical picture, which can include impaired emptying secondary to a weak detrusor contraction. Patients with diabetic cystopathy may progress to develop acontractile bladders with diminished urinary flow, discussed further below. The classic description of diabetic cystopathy is that of impaired of bladder sensation leading to increased bladder capacity, increased PVR volume, and decreased detrusor contractility. However, these are not the most common findings among patients with diabetes and voiding symptoms. In a study of 182 patients with diabetes who underwent urodynamic testing, 55% had detrusor overactivity compared to the 23% that had impaired detrusor contractility;10% had acontractile bladders.10
Chronic obstruction and overdistension can also cause alterations in the detrusor muscle resulting in impaired detrusor contractility. Some of the best urodynamic data available for chronic obstruction resulting in myogenic failure come from male babies with posterior urethral valves. These are the children who have a congenital obstruction of their urinary outflow tract secondary to a thin membrane in the urethra. Despite of being treated at a very early age, these children will develop poorly functioning detrusor muscles on urodynamics performed years later. Overdistention and obstruction that is present in utero, and early life, can be devastating to the function of the adolescent bladder.13-14
Other disease processes cause myogenic injury in adults. A retrospective study carried out in patients with large-capacity bladder (greater than 700 mL) showed almost 50% of these patients had urethral obstruction. In spite of the large-volume bladder, 17% were noted to have normal voiding characteristics, suggesting that overdistention alone is not sufficient to cause impaired contractility in all patients.15 In addition, 24% of patients had impaired detrusor contractility, and 11% had acontractile bladders.
A study of women with pelvic organ prolapse (with or without voiding symptoms) found that urodynamics obtained preoperatively showed impaired contractility in 13% of women (eight out of 60 women).16 The study controlled for grade of prolapse (grades 1–2 vs grades 3–4) and found no statistical difference between the women with mild prolapse, grades 1–2, and women with moderate-to-severe prolapse, grades 3–4 (14% vs 12% respectively, P > 0.5). The same study showed urinary obstruction in 33% of the women with prolapse; obstruction was much more likely when women were compared by stage of prolapse (6% in grades 1–2 vs 72% in grades 3–4, P < 0.001). There are myriad factors influencing these urodynamic findings, but impaired contractility can exist in the prolapse population. Even iatrogenic causes of obstruction, such as a midurethral sling, have been implied in causing long-term impaired detrusor contractions even after the obstruction is relieved.17
Pharmacologically induced detrusor underactivity occurs when the strength, duration, and/or frequency of spontaneous and pathologic detrusor contractions can be influenced by various pharmacologic agents. These agents either contribute to weakening a contraction of a detrusor muscle that is already underactive or cause de novo underactivity. The clinical scenario and agent used will dictate the clinical significance of this detrusor underactivity. Women are much less likely to develop urinary retention than their male counterparts. As such, population-based evidence is limited on the effect of medications on female bladder emptying. Based on the mechanisms of action, increased PVR, urinary frequency, decreased urinary stream, and increased straining are all likely affected by multiple medications. Medications may also adversely affect bladder emptying by increasing resistance of the bladder outlet through their effects on the bladder neck urethra and sphincter.
As the primary drug class used to treat detrusor overactivity, antimuscarinics have been widely studied for their effect on the bladder. Muscle strips taken from normal human bladders can be contracted by cholinergic muscarinic agonists and by stimulation of intrinsic cholinergic nerves. This contraction can be completely aborted in human by the use of atropine, a competence antagonist for the muscarinic acetylcholine receptor.18 In fact, antimuscarinic agents have been broadly used to treat conditions of overactive bladder, detrusor overactivity, and impaired compliance because of their effect on detrusor muscle. M1, M2, and M3 muscarinic receptors subtypes have all been found in the urinary bladder and have been the target of numerous therapies.19 To date, all antimuscarinic therapies utilized for the treatment of overactive bladder list urinary retention as a potential side effect. Urinary retention lies on one end of the spectrum of impaired contractility. More commonly seen are elevated PVRs, increased cystometric capacity, and increased compliance, which are desired outcomes with effective therapeutic use of these agents.
Another commonly used class of medications that may affect bladder emptying are α-adrenergic agents. Study of anesthetized rats showed a clear dose-response curve to intravenous phenylephrine administration increasing urethral resistance.20 Here too, the adverse effect on bladder emptying has led investigators to question if α-antagonists can be utilized to improve bladder emptying.21 These medications are commonly used in male patients, but results in women have been mixed. Larger studies, in a well-defined population, with appropriate outcome measures are necessary before more widespread use can be advocated.
Narcotics have also been recognized to contribute to impaired bladder emptying. Direct injection of morphine into the epidural space was carried out in healthy male subjects and demonstrated urodynamic relaxation of the bladder, regardless of the dose of morphine used, with improvement in contractility after treatment with a competitive antagonist such as naloxone.22 Another similar study of epidural morphine injection resulted in urinary retention of 90% of patients. No patients experienced retention from a similar intravenous dose.23 From work with a rat model, the proposed effect of intrathecal morphine on impaired bladder emptying results from increased tone of the external urethral sphincter.24 Systemic narcotics have also been shown to contribute to the risk of urinary retention. A study of patients undergoing hemorrhoidectomy revealed greater narcotic use was an independent risk factor of urinary retention (odds ratio 1.8, P = 0.01).25 The effect of opiates and opiate receptor analogs on micturition is likely multifactorial. Opiates impair the sensation of bladder filling by partially inhibiting parasympathetic nerves that innervate the bladder.26 There does also appear to be a direct effect on detrusor contractility.27 Further, opiates’ effect on the lower urinary tract have been attributed to increase the tone of the sphincter by sympathetic overstimulation. Any combination of these mechanisms can lead to impaired bladder emptying.
There are numerous other classes of agents that exert effect on bladder action. Their mechanisms of actions are varied, as are their effects on bladder emptying, as it contributes to dysfunctional voiding in a clinically relevant way. A summary of some commonly encountered medications, their effect on the bladder, as well as their mechanism of action can be found in Table 8-2.
Drugs that Affect the Bladder
| Classification | Examples | Pharmacologic Action |
|---|---|---|
| Anticholinergic agents | Atropine, oxybutynin, glycopyrrolate, tolteradine, solifenacin, darifenacin, fesoterodine, trospium, hycosamine (Antihistamine agents can cross the blood-brain barrier and have anticholinergic activity.) | Inhibit muscarinic receptors, thereby reducing response to cholinergic stimulation. Clinically used to reduce pressure during filling in cases of impaired compliance, decreased amplitude duration, and frequency of involuntary unstable bladder contractions. |
| Smooth muscle relaxants | Dicyclomine, flavoxate | Direct relaxation of smooth muscle; reduces intravesical pressure during filling and severity and presence of unstable bladder contractions. Most of these agents have anticholinergic action. |
| Calcium antagonists | Diltiazem, nifedipine, verapamil | Reduces entrance of calcium during action potential, thereby reducing the magnitude of spikes during unstable bladder contraction. |
| Potassium channel openers | Cromakalim, pinacidil | By increasing the membrane potential, myogenic initiation of unstable bladder contractions is reduced. |
| Prostaglandin synthesis inhibitors | Flurbiprofen | Prostaglandins have been implicated in increasing smooth muscle tone and inducing spontaneous muscle activity, thereby inhibiting their production and synthesis; bladder relaxation and decreased spontaneous activity may be promoted. |
| β-Adrenergic agonists | Isoproterenol, terbutaline | Direct bladder relaxation can induce activation of β-adrenergic receptors. These are stimulated by norepinephrine release in the sympathetic nerve terminals. |
| Tricyclic antidepressants | Amitriptyline, imipramine | Effects on bladder muscle are from anticholinergic properties, direct smooth muscle relaxation, and norepinephrine reuptake inhibition. |
| α-Adrenergic agonists | Ephedrine, pseudoephedrine, midodrine, phenylpropanolamine | α1a receptors are found at the bladder neck, and stimulation may contribute to increasing bladder outlet resistance. α1a and αd are found in the human bladder and α1A in the urothelium. These agents may exert a direct excitatory effect on bladder smooth muscle, and indirectly enhance acetylcholine release. |
| Afferent nerve inhibitors | Dimethyl sulfoxide, capsaicin, resiniferatoxin | Reduce sensory input from the bladder, thus increasing bladder capacity and reducing bladder instability |
| Estrogen | Estradiol | Aside from increasing thickness of urothelial mucosa, there may be an effect on increasing adrenergic stimulation, resulting in an increase in blood flow. |
| Neurotoxins | Botulinum toxin | By blocking SNAP-25 fusion with plasma membrane, terminal nerve release of acetylcholine is inhibited. This leads to decreased muscle contractility and muscle atrophy. |
An acontractile bladder, as defined by the ICS, is one that cannot be demonstrated to contract during urodynamic studies.2 There are numerous causes for acontractile bladder. One of the most common causes of acontractile detrusor is cauda equina syndrome. The cauda equina is formed by the nerve roots caudal to the termination of the spinal cord. Cauda equina syndrome results from compression of these nerves. In a study of patients with chronic cauda equina syndrome, the most common lower urinary tract finding was impaired bladder emptying, which was found in 92% of women; 54% of women had a voiding cystometry consistent with an acontractile detrusor; 31% exhibited detrusor underactivity; and the remaining 15% had normal detrusor contractions.29 Other studies have shown a high prevalence of acontractile bladder in posttraumatic lower spinal cord–injured patients. A study investigated the correlation between the level of the spinal lesion and urodynamic findings, and reported that nearly 86% of patients with sacral injuries had acontracile bladders.30
Although urinary retention, as part of cauda equina syndrome, is usually seen from central lumbar disc prolapse, acontractile bladder has also been noted with lateral lumbar disc prolapse or lumbar spondylosis. A small study of patients who underwent urgent spinal decompression for urinary retention from lumbar disc prolapse within 48 hours, who had both preoperative and postoperative urodynamics, did not regain detrusor function postoperatively with follow-up ranging from one month to six years. However, most patients could empty their bladder with straining or changing their voiding postures postoperatively.31
There are other etiologies for acontractile bladders that are not compressive or traumatic in nature. One of these is cerebral vascular accidents (CVA). Acute detrusor areflexia can occur in up to 6% of patients who have a CVA. However, detrusor overactivity is the most common finding on filling cystometrogram.32
Certain infectious processes have been found to be associated with acontractile bladder. The spirochete that causes Lyme disease has been documented to result in acontractile bladder. In addition, acquired immune deficiency syndrome can involve both central and peripheral nervous system derangements, with urinary retention being the most common presenting symptom of this manifestation. Opportunistic infections that affect patients with compromised immune systems also result in voiding dysfunction. Voiding dysfunction related to neurosyphilis was seen in the era before the use of penicillin. Other benign inflammatory diseases of the nervous system have been associated with acontractile bladder. This can occur from a central inflammation resulting in acute spinal shock, termed meningitis retention syndrome, or from referral inflammation resulting in alteration in function of pelvic nerves, or sacral herpes.33
An acontractile bladder can also be seen in conditions where the urethral sphincter fails to relax, such as Fowler syndrome, explained further below. Studies in cats showed that afferent activity from the urethral sphincter results in suppression or inhibition of detrusor activity.34 This phenomenon may be explained by the “guarding reflex” that starts with voluntarily contraction of the urethral sphincter to abort the sensation of urgency and suppress detrusor activity. Conversely, when the urethral sphincter fails to relax, this can prevent voluntary contraction of the bladder.
To this point, voiding dysfunction has been discussed in terms of processes that can affect the bladder and how they may negatively impact the voluntary expulsion of urine. However, there are processes that also affect the outlet of the bladder, and can also have a negative impact on the micturition phase of voiding. The processes that are primarily a failure of the striated sphincter to relax will be described below.
One cause of a failure of the sphincter to relax, causing urinary retention, is known as Fowler syndrome. This syndrome was once known as psychogenic urinary retention until the 1980s, when electromyography (EMG) studies showed abnormalities of the striated muscle of the external sphincter.35 Though the pathophysiology is still not fully elucidated, it is thought that the urinary retention is secondary to a continuous involuntary contraction of the striated sphincter. This, in turn, causes an inhibitory effect on detrusor contractions. Women with Fowler syndrome are young (between ages 15 and 30), and present with painless urinary retention of greater than 1 L. Urologic, gynecologic, and neurologic diseases must be ruled out as potential causes of this urinary retention. The women are healthy; however, Fowler disease has also been associated with polycystic ovarian syndrome and endometriosis. Woman with Fowler syndrome may note that additional straining does not help them empty their urinary bladder. Some clinicians have also described a phenomenon, when a urethral catheter is removed, that there is “something gripping the catheter.” This is likely describing the resistance caused by a tonically contracted striated sphincter. Urethral pressure profiles will show elevated urethral pressures. Increased sphincter volume can be noted on ultrasound and, EMG studies of the striated sphincter will show impaired relaxation.36
Psychogenic urinary dysfunction is usually accompanied by obvious psychiatric/psychologic features. This is a diagnosis of exclusion, and even if a case suggests psychogenic urinary dysfunction, nonpsychogenic urinary dysfunction pathology must be explored. A urodynamic study of patients with psychogenic urinary dysfunction found this disorder to be rare (0.7% among 2,300 urodynamic cases reviewed) with the main urodynamic findings of increased bladder sensation and acontractile detrusor.37 Symptomatically, patients had situational overactive bladder and/or difficult urination, and, in some cases, extremely infrequent voiding. Pain with urination has also been suggested as a cause for learned failure of sphincteric relaxation resulting in voiding phase dysfunction. This may be pain secondary to postoperative urologic/gynecologic procedures, or pain related to an infectious etiology.
Voiding dysfunction can also be caused by obstruction at the bladder outlet. This includes a wide variety of pathologies at the bladder neck. These processes can be divided into two categories: anatomical or functional. In anatomical obstruction, the cause can often be seen on physical examination, imaging, or endoscopy (eg, pelvic organ prolapse, urethral cancer, urethral stricture, and so on). The diagnosis of function obstruction can only be made during voiding, and thus urodynamics is required.
Iatrogenic causes of urinary obstruction can result from diagnostic instrumentation, catheterization, radiation, pelvic surgery, and antiincontinence surgery. Urethral stricture accounts for 4% to 13% of cases of female bladder outlet obstruction presenting with LUTS.38,39 A female urethral stricture has been defined as a fixed anatomic narrowing between the bladder neck and distal urethra of less than 14 French, preventing instrumentation. This was chosen empirically as the lower limit of normal urethral caliber in women, and the clinical observation of the lack of LUTS in such patients. Causes of obstruction are varied and have been attributed to trauma including pelvic fracture or childbirth, periurethral surgery, urethral instrumentation, radiation, infectious urethritis, and malignancy.
The true incidence of obstruction from anti-incontinence surgery is unknown, but has been estimated between 2.5% and 24%. The midurethral sling data show that obstruction requiring intervention is probably in the 1.7% to 4.5% range.40 Others have suggested that the rate of stricture and an intervention may be higher. One study, retrospective in nature, showed that from a group of 267 women, 22 (8%) were performing clean intermittent self-catheterization as a result of tension-free vaginal tape surgery at six months.41 Some have also argued that the risk of obstruction secondary to a midurethral sling is higher in patients who undergo concomitant pelvic organ prolapse repair. The risk of intervention due to obstruction after receiving a midurethral sling was 8.5% in a study of 140 patients who underwent a transvaginal repair for stage II to IV pelvic organ prolapse.42
The diagnosis of obstruction in women after stress incontinence surgery is strongly suggested by history and the correlation of symptoms to the timing of the surgery. Obvious signs of obstruction may be complete or partial retention of urine but other symptoms are suggestive. Fifty-one women who underwent urethrolysis were queried about what their presenting symptoms were. Storage (irritative) symptoms were the presenting symptoms in 75%, voiding (obstructive) symptoms in 61%, de novo urge incontinence in 55%, need for catheterization in 40%, persistent retention in 24%, recurrent urinary tract infection (UTI) in 8%, and painful voiding in 8%.43 Other studies of patients who have undergone urethrolysis have noted that 60% to 84% of patients have voiding (obstructive) symptoms and 55% to 75% have irritative storage symptoms.44 Thus in patients who present with de novo voiding and/or storage symptoms following surgery, the diagnosis of obstruction should be considered.45
Periurethral bulking agents used for intrinsic sphincter deficiency can also result in impaired bladder emptying or obstruction. One study looked at the route of bulking and the effect on urinary retention. Women were randomized to periurethral injection versus transurethral injection, and a higher rate of retention after the periurethral approach was reported (30% vs 5%, P < 0.05).46
Pelvic organ prolapse has been shown to cause bladder outlet obstruction. This is due to a “kinking” affect of the urethra. Bladder outlet obstruction was found in 4% of patients with grade 1 or 2 cystocele and 58% of patients with grade 3 or 4 cystocele (P < 0.001).16
The retroverted impacted gravid uterus has been reported as a rare cause of acute urinary retention. One study looking at ultrasound findings of urinary retention in patients with a gravid retroverted uterus suggests that the retention is caused by the cervix compressing the lower bladder and interfering with drainage to the urethra. The imaging of these five women showed that the urethra itself was not compressed or distorted.47
Primary female urethral cancer is quite rare. More commonly, malignancy of the urethra is by direct extension from a malignancy within a urethral diverticulum or an adjacent organ. Surveillance epidemiology and end results (SEER) data reported 540 cases of primary urethral cancer in the United States from 1973 to 2002.48 Urethral cancers are usually asymptomatic; however, the symptoms can include irritative voiding symptoms, or bleeding. Although rare, cases of urinary retention have been reported.
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