Overactive Bladder
Jennifer A. Reinhold
Overactive bladder (OAB) is a highly prevalent yet under-reported condition that transcends the boundaries of race, gender, and socioeconomic class. OAB is loosely defined by the International Continence Society (ICS) as a constellation of symptoms that include primarily urinary urgency usually accompanied by frequency (voiding eight or more times per 24 hours) and nocturia (awakening two or more times at night to void), with or without urge urinary incontinence (UUI). It is a symptom syndrome and not a discrete diagnosis. The most recent data suggest that OAB affects between 16% and 17% of adults in the United States, or about 34 million people. However, given the substantial underreporting and the inherent challenges in identifying sufferers of OAB, the actual prevalence is likely markedly higher. Women and men tend to be affected by OAB proportionately; however, women are more likely than men to present with the symptom of incontinence as part of their clinical picture. The incidence of OAB increases linearly with age and is predicated on a number of factors that are impacted by aging. However, OAB with or without incontinence is not considered a normal part of aging; OAB symptomatology and any instance of urgency are always considered pathologic.
OAB syndrome has extensive ramifications with respect to morbidity, mortality, and economic impact. A preponderance of literature supports the assertion that OAB is associated with increased rates of depression, decreased self-esteem, social isolation, general fragility, and falls and fracture. Upon development of OAB symptoms, patients tend to engage in avoidance behaviors in order to escape the social stigma and embarrassment associated with urinary incontinence (UI) or urinary urgency. Eventually, this translates into substantial lifestyle changes and the potential for social isolation. Total costs attributable to OAB are estimated to be $65.9 billion ($49.1 billion direct medical, $2.3 billion direct nonmedical, and $14.6 billion indirect) (Ganz et al., 2010). A leading cause of morbidity in the elderly population and the most commonly cited reason for assisted living and long-term care facility admission, OAB needs to be assessed in the primary care setting preemptively.
The terms OAB, detrusor overactivity (DO), and UI are frequently used interchangeably erroneously. UI is a possible symptom as part of the symptomatology construct that constitutes OAB; it does not necessarily need to be present in patients diagnosed with OAB. While urgency is the cardinal symptom of OAB and must be present in order to yield a diagnosis of OAB, only about 25% to 35% of patients experience incontinence as well. DO implies an involuntary and inappropriate contraction of the bladder; however, it is considered a surrogate marker of OAB that may or may not correlate with urgency. DO is further delineated into idiopathic (absence of an identifiable cause) or neurogenic (an underlying neurological condition, deficit, or injury is the causative factor). There is considerable overlap between nonpharmacologic and pharmacologic treatments for OAB, UI, and DO; therefore, UI subtypes will be discussed. The accepted nomenclature for UI differentiates between the underlying pathophysiology and the nature of the urine loss. UUI implies a strong and sudden urge to urinate that cannot be deferred and results in involuntary loss of urine. Stress urinary incontinence (SUI) occurs when an internal or external force impacts the bladder or the musculature that supports it. Common examples of such pressures include coughing, sneezing, heavy lifting, or prolapsed pelvic organs. Mixed UI is a combination of both SUI and UUI. The historical term overflow incontinence, which suggested some level of obstruction or voiding difficulty, has been replaced with bladder outlet obstruction (BOO) and is no longer part of the classification schema.
CAUSES
The exact cause of the OAB symptom constellation is multifactorial and not completely elucidated. There are numerous underlying anatomic, physiologic, and comorbidity-related factors that precipitate or exacerbate OAB. The majority of cases are considered idiopathic, with the remainder being attributed to myogenic or neurogenic causation.
PATHOPHYSIOLOGY
The bladder and the corresponding micturition cycle are controlled by a complex, coordinated interplay among the central nervous system (CNS), peripheral nervous system, and the anatomic components of the lower urinary tract (LUT). The LUT is composed of the bladder, urethra, bladder outlet, internal and external urethral sphincters, and the musculature of the pelvic floor (Figure 34.1). The discord between the continuous production of urine (1 to 2 L/d) and the episodic nature of voiding necessitates the storage of urine. The bladder (detrusor muscle) is a highly compliant, viscoelastic hollow organ that expands to accommodate the storage of urine while maintaining a constant pressure throughout this filling phase. As the bladder fills, it maintains a pressure that is lower than that of the urethra, therefore facilitating the development of a pressure gradient that prevents urine from being expelled. The normal urge to void is under voluntary control, and therefore, only when the bladder reaches a critical volume, or about 75% of total capacity, will an individual feel the desire to void. This urge, which is different from pathologic urgency and is under different neural control, can be deferred until an appropriate time. Upon conscious and deliberate urination, the urethral resistance decreases and phasic contractions in the bladder result in increased bladder pressure and the subsequent voiding of urine.
FIGURE 34.1 M3 receptors are coupled to G proteins, which activate phospholipase, generating inositol triphosphate (IP3). IP3 causes the release of stored Ca2+, which stimulates bladder contraction. |
The LUT is innervated by efferent and afferent neuronal complexes involving sympathetic, parasympathetic, and somatic nerves. The sympathetic nervous system primarily stimulates urethral sphincter closure and detrusor relaxation during filling, while the parasympathetic system influences contraction of the detrusor and relaxation of the urethral sphincters during the emptying phase. Somatic innervation maintains the tone of the striated pelvic floor muscles and the external urethral sphincter (Table 34.1). The bladder is continuously bombarding the CNS with afferent signals during the filling phase via Aδ fibers and C fibers. These normal impulses indicate when the bladder is filling and also when it is nearing capacity. The impulses are transmitted to higher brain centers such as the cortex, pons, and brain stem, which also exert some level of control over micturition. The sensations generated by this neurotransmission will result in variable degrees of the normal urge to urinate. The Aδ fibers generally respond to the mechanical stretch of the bladder during the filling phase. However, during pathologic conditions, it is thought that the unmyelinated C
sensory fibers may precipitate abnormal OAB sensations. The C sensory fibers are dappled with vanilloid receptors (which can be stimulated by capsaicin), purinergic receptors or P2X2 and P2X3 (which can be stimulated by adenosine triphosphate), and neurokinin receptors (which can be stimulated by neurokinin A and substance P). (see Figure 34.2).
sensory fibers may precipitate abnormal OAB sensations. The C sensory fibers are dappled with vanilloid receptors (which can be stimulated by capsaicin), purinergic receptors or P2X2 and P2X3 (which can be stimulated by adenosine triphosphate), and neurokinin receptors (which can be stimulated by neurokinin A and substance P). (see Figure 34.2).
TABLE 34.1 Bladder and Urethral Innervation | ||||||||||||||||||||||||||||||||||||||||
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Acetylcholine-mediated activation of muscarinic receptors is the predominant physiologic mediator of detrusor
contraction. Muscarinic receptor subtypes M1, M2, and M3 are found in the urinary bladder; however, it is the M3 subtype that is primarily responsible for bladder contraction. These receptors, particularly the M3 subtype, have become drug targets for purposes of treating OAB.
contraction. Muscarinic receptor subtypes M1, M2, and M3 are found in the urinary bladder; however, it is the M3 subtype that is primarily responsible for bladder contraction. These receptors, particularly the M3 subtype, have become drug targets for purposes of treating OAB.
Any aberration of any individual component or combination of components involved in the micturition reflex can result in OAB or UI, as can separate comorbid conditions or physiologic states. Transient and reversible conditions or behaviors may contribute to symptoms consistent with OAB, namely, increases in fluid intake or increases in caffeine or alcohol consumption. Benign prostatic hyperplasia (BPH) or obstruction can manifest in incontinence. Sacral nerve damage can lead to urinary retention. Irrespective of the etiology of OAB, the common themes include increased bladder pressure at low volumes during filling, altered response to stimuli, amplified myogenic activity and contraction, and changes in the smooth muscle anatomy.
Owing to the poor electrical coupling between smooth muscle bundles in the bladder, the highly innervated bladder is able to ignore some of the errant impulses that would otherwise cause unwanted contraction. Patchy denervation and morphologic changes in the electrical coupling may result in bladder hypertrophy and incomplete emptying. Abnormal micturition can be stimulated by damage to the afferent neurons in the dorsal root ganglia as well, which can then confer an abbreviated delay in the micturition reflex. Ischemic conditions such as diabetic neuropathy, peripheral vascular disease, and urethral stricture may also result in compromised blood flow and ultimately neuronal death with subsequent detrusor hyperactivity. Inevitable physiologic changes that occur during the aging process may also contribute to impaired cortical inhibition of bladder contraction. Stroke, Alzheimer disease, and multiple sclerosis have been implicated in contributing to the disease process as well. Nonneurogenic conditions may also yield OAB symptoms; polyuria may be produced by uncontrolled diabetes, and nocturia may be precipitated by sleep apnea (Box 34.1).
Once OAB symptoms have emerged, a self-propelling cycle of factors can further exacerbate the condition. Urgency, a central feature of OAB, increases the frequency of micturition and therefore reduces the volume of each micturition provided that fluid intake remains constant. This sometimes leads to incomplete bladder emptying and subsequent residual volume that promotes the urgency and increased frequency of urination. Similarly, DO can result from neurogenic or myogenic causes. The contractions tend to be weak, which results in incomplete bladder emptying, a reduced bladder capacity, and therefore increased urinary frequency.