The International Continence Society (ICS) has defined bladder storage abnormalities that include urinary incontinence, its subtypes, and overactive bladder (OAB) syndrome.¹ Although urinary incontinence is simply “involuntary loss of urine,” its three major subcategories are stress urinary incontinence (SUI), urgency urinary incontinence (UUI), and mixed urinary incontinence (MUI). SUI is the “involuntary loss of urine on effort or physical exertion or on sneezing or coughing.”¹ UUI, the focus of this chapter, is incontinence associated “with the sensation of a sudden, compelling desire to void that is difficult to defer.”¹ UUI is a subset of OAB syndrome, defined by the ICS as urinary urgency, usually accompanied by frequency and nocturia, with or without UUI in the absence of urinary tract infection or other obvious pathology.¹ Lastly, MUI is a combination of SUI and UUI and is defined as “involuntary loss of urine associated with urgency and also with effort or physical exertion or on sneezing or coughing.”¹ The interrelationships between OAB, SUI, UUI, and MUI are illustrated in Figure 6-1.

Attempts to ascertain OAB and UUI prevalence and incidence have been hampered by lack of standardization of definitions including the frequency or severity of symptoms in epidemiologic studies. Nonetheless, based on a recent summary, estimates of OAB and UUI prevalence in Europe, Asia, and the United States are relatively consistent.² The prevalence of OAB in the United States is approximately 15% and UUI is as high as 11%.² Occurrence of both UUI and OAB is associated with increasing age (Figure 6-2). UUI incidence in the United States is four to five women per thousand in the 35- to 55-year age group,³ and increases to 7 to 17 women per thousand^4,5 in women older than 60 years. The few studies that address remission of UUI report annualized remission rates ranging from 11% to 22.7% in older women.^4,5 These reports and other recent work indicate that UUI is a dynamic state over the short term.^4-6 Although no studies have evaluated the lifetime natural history of OAB and UUI, data from the Agency for Healthcare Research and Quality (AHRQ) suggest that over the long term women ultimately develop persistent symptoms.²

Approximately one-third of women with incontinence are estimated to have MUI⁷ with prevalence varying from 27% to 36%.^8,9 Similar to UUI, MUI prevalence also increase with age (Figure 6-2).¹⁰ The prevailing opinion is that MUI represents a more severe form of incontinence than pure UUI, and although women with MUI are more likely to seek care for their symptoms, their incontinence is more refractory to treatment.^7,9-12

The spectrum of OAB, including UUI and MUI, is an increasingly pressing problem due to the aging population. It extracts a personal toll on individuals and poses an economic burden upon society. It causes modification in work and social habits, which range in significance from bathroom mapping and sleep disturbance to social isolation.² UUI, MUI, and OAB are associated with depression, diminished self-esteem, sexual dysfunction, and decreased work productivity.^2,13 The OAB population, which numbered 34 million in 2007, is projected to increase to 41.9 million in 2020.¹⁴ OAB is also projected to consume 76.2 billion dollars in 2015 and 86.2 billion dollars by 2020.¹⁴ OAB’s personal, social, and medical costs make it the principal contributor to the financial burden of bladder storage disorders.

Introduction

The lower urinary tract, the bladder and its outlet, has two functions: the coordinated storage and expulsion of urine. During storage, the pliable bladder smooth muscle, or detrusor, relaxes while the urethra (smooth muscle), the external urethral sphincter (EUS) (skeletal muscle), and the bladder neck contract. During voiding, the bladder contracts and the outlet relaxes. These seemingly simple events require complex neurologic coordination.

UUI symptoms can be caused by several mechanisms. Urinary urgency and urgency incontinence can be a manifestation of a neurogenic bladder caused by conditions such as stroke, spinal cord injury, multiple sclerosis, or Parkinson disease. In men, UUI symptoms are most commonly related to obstructive pathology of the prostrate. Traditionally, UUI in women is thought to be due to idiopathic detrusor overactivity and its mechanism is incompletely understood.¹⁵ Abnormalities of bladder muscle and/or epithelium and their chemical products as well as neurologic dysfunction may contribute to its occurrence.^16,17

Normal Voiding and Storage Physiology and Anatomy

A review of normal voiding and storage physiology of the bladder assists in understanding its dysfunction. Motor, or efferent, control of the bladder depends on autonomic and somatic nerves. Autonomic nerves, both the parasympathetic and sympathetic, control lower urinary tract smooth muscle. Somatic nerves control lower urinary tract skeletal muscle.

The autonomic nervous system’s sympathetic and parasympathetic components function reciprocally. Sympathetic stimulation results in urine storage, and parasympathetic stimulation results in voiding. Sympathetic efferents originate in the thoraco-lumbar spinal cord. Most sympathetic preganglionic nerves synapse with postganglionic nerves in the hypogastric¹⁸ or inferior mesenteric plexus¹⁹ and travel via the hypogastric nerve to the bladder.^18,20 Parasympathetic efferents originate in the parasympathetic nucleus at spinal cord levels S2–S4. The preganglionic efferents travel via the pelvic nerve and synapse in the pelvic plexus or synapse with postganglionic nerves located in the bladder wall (Figures 6-3 and 6-4).²¹

Neurotransmitters are responsible for preganglionic (nerve-to-nerve), and postganglionic (nerve-to-muscle) communication. The major sympathetic postganglionic neurotransmitter is norepinephrine (NE), whereas the major parasympathetic postganglionic neurotransmitter is acetylcholine (ACh). NE stimulates bladder β-sympathetic receptors resulting in bladder relaxation and urethral α-sympathetic receptors resulting in urethral contraction; the net effect is urine storage. ACh release stimulates the bladder’s muscarinic parasympathetic receptors (primarily M-2 and M-3) resulting in detrusor contraction. The importance of ACh release in urethral relaxation is less certain; local release of nitric oxide (NO) also probably plays a significant role. In either case, the net effect of urethra dilation and ACH-mediated detrusor contraction is voiding (Figures 6-3, 6-4, and 6-5).²¹

Somatic nerves control lower urinary tract skeletal muscle, including the EUS. Somatic efferents originate in Onuf nucleus in the ventral portion of S2–S4 and travel in the pudendal nerve to the EUS (Figure 6-3).¹⁹ More recent work reports an additional pathway of innervation via the levator ani nerve.²²

The sensory, or afferent, nerves in the bladder include unmyelinated C-fibers and myelinated A-δ afferents. At birth, C-fiber afferents predominate¹⁸ but as the nervous system matures, A-δ fibers gain importance.^18,23 A-δ fibers transmit bladder filling signals to the central nervous system (CNS) when stretch receptors are activated. C-fibers transmit unpleasant sensations such as pain or discomfort to the CNS.¹⁸ Neural insult, such as what occurs following infection, inflammation, or trauma, may cause A-δ fibers to revert to C-fibers and contributes to the development of OAB, UUI, and painful bladder syndrome.¹⁹

Anatomically, the afferent system of the lower urinary tract varies from the motor or efferent system. Although afferents travel with the autonomic and somatic efferent nerves, they are not segregated into sympathetic and parasympathetic autonomic and somatic pathways until they reach the dorsal root ganglia, located just outside the spinal cord.²⁴ Nerves that originate in the bladder and urethra travel with the pelvic, hypogastric, and pudendal nerves to cell bodies in the dorsal root ganglia. It is here that afferents differentiate into sympathetic, parasympathetic, or somatic tracts.¹⁹ In the spinal cord, autonomic and somatic afferents synapse with efferents to the lower urinary tract and can initiate urinary reflex arcs. Lower urinary tract afferents also synapse with secondary afferents that travel to the brainstem and upper CNS, which modulate voiding responses.²⁰

The supraspinal CNS modulates the previously described reflexes and determines whether it is an appropriate time to void. Recent reviews of brain imaging correlated with laboratory investigation have proposed a simplified model of CNS modulation of bladder storage and micturition (Figures 6-6 and 6-7).^25,26 Bladder afferents transmit information from the spinal cord to the periaqueductal gray matter (PAG) in the midbrain (Figure 6-6). The PAG, composed of gray matter around the cerebral aqueduct, in turn relays neural signal to regions in the cerebral cortex, including the insula, anterior cingulate gyrus (ACG), and prefrontal cortex (Figure 6-7). The PAG also regulates output from these regions to the pontine micturition center (PMC) (Figures 6-6 and 6-7). This output can inhibit voiding until voiding is appropriate, at which time the PMC is disinhibited and voiding occurs^25-28 (Figure 6-7). Urinary storage disorders may be caused by dysfunction at numerous points in this complex pathway.

Pathophysiology of Storage Disorders

Idiopathic Urgency Urinary Incontinence

A number of abnormalities probably contribute to what we currently classify as idiopathic UUI. These include alterations in neurotransmitters, sensory nerve fibers, and patterns of brain activation. For example, UUI is associated with increased release of nonadrenergic noncholinergic (NANC) neurotransmitters in the bladder, such as ATP.^17,29 ATP is an alternative neurotransmitter that is increased in idiopathic detrusor instability, and its release may explain why muscarinic blockade fails in some UUI patients.³⁰ Injury or insult to sensory fibers in the bladder also potentially contributes to UUI. Following infection, inflammation, or trauma, A-δ fibers may revert to C-fibers causing hyperexcitability of lower urinary tract afferents and subsequent detrusor overactivity.¹⁹ Additionally, a variety of potential mediators that affect neural activity can be synthesized within the bladder wall itself, and likely play a role in increased detrusor contractility.¹⁶ Lastly, the advent of improved brain imaging has allowed research to focus on the role of the CNS in mediating UUI symptoms. The brain’s handling of lower urinary tract afferent signals, with increased limbic and decreased prefrontal cortical activation and alterations in brain connectivity in women with UUI, may be associated with decreased inhibition of voiding and UUI.^25-28

Neurogenic Bladder

Spinal cord injury can result in lower urinary tract dysfunction. Spinal trauma superior to the lumbosacral region eliminates voluntary and supraspinal control of the bladder and results in “spinal shock” with bladder areflexia and urinary retention. After a variable period, commonly six to eight weeks, detrusor hyperreflexia and neurogenic detrusor overactivity ensue.^16,20,31 Despite the bladder’s overactivity, voiding may be ineffective due to development of detrusor-sphincter-dyssynergia caused by concomitant urethral and detrusor contractions. The belief is that the normally quiescent C-fiber afferents trigger reflex pathways, which result in detrusor hyperreflexia due to morphologic, chemical, and electrical changes in bladder afferents following trauma.³¹

Neurologic illness, including multiple sclerosis (MS) and Parkinson disease, is also commonly associated with neurogenic detrusor overactivity. MS can wax and wane but is often progressive as increasing bladder dysfunction accompanies increased spinal cord involvement. MS disrupts supraspinal control of the urinary tract and activates C-fibers³² with resultant detrusor overactivity and detrusor-sphincter-dyssynergia. Detrusor overactivity in Parkinson disease may be due to a central defect in dopaminergic control of micturition. Dopamine one, which inhibits micturition, is depleted in the midbrain in Parkinson disease and results in detrusor overactivity.³³

Cerebrovascular accidents (CVA) frequently result in urinary incontinence. Approximately 40% of stroke victims are incontinent one week following a CVA and 15% to 20% have persistent incontinence at hospital discharge.³⁴ The size, location, and severity of a CVA affect the degree and type of lower urinary tract dysfunction.³⁵ In animal experiments, occlusion of the middle cerebral artery resulted in damage to the cortex and putamen with decreased bladder capacity.³⁶ In clinical practice strokes often damage centers that inhibit micturition resulted in detrusor instability.³⁷

Obstruction

Bladder outlet obstruction, though common in men due to prostatic hypertrophy, is less common in women and usually occurs due to advanced pelvic organ prolapse or anti-incontinence procedures. In a multicenter study of women who underwent colpocleisis to treat prolapse, 41% of women had bothersome OAB and UUI preoperatively. In such patients outlet obstruction may cause stretch-induced bladder damage that upregulates C-fiber activity, facilitating the voiding reflex.¹⁶ Surgical relief of the outlet obstruction can improve UUI. Among the women treated with colpocleisis above, the prevalence of UUI decreased to 15% at one-year follow-up. Surgical series report resolution of UUI in 75% to 82%^38,39 of women treated with anterior vaginal prolapse repair. These clinical findings indicate that anterior prolapse–related UUI may be reversible in many women.

Mixed Urinary Incontinence

Mixed UI is the combination of both UUI and SUI and constitutes one-third of incontinence cases, most prevalent in the elderly. It is more refractory to treatment than other incontinence types, in part because its etiology remains incompletely understood.⁷ One hypothesis is that detrusor overactivity is initiated by increased afferent activity in response to the presence of urine within the bladder neck, or funneling, that occurs commonly in SUI.⁴⁰ The hypothesis is supported by laboratory work showing that urethral fluid infusion cause reflexive detrusor contractions.⁴¹ This concept, “stress hyperreflexia” (Figure 6-8),⁴² is supported by both clinical and laboratory observations. Alleviation of stress hyperreflexia may account for the observation that surgical repair of SUI predominant MUI can also cure UUI; UUI resolves in as many as 40% to 50% women with MUI treated with stress incontinence surgery.⁷ Although surgical treatment of MUI may resolve UUI in selected patients, surgery also has the potential to irreversibly worsen UUI. Accordingly, the current recommendations are to initiate treatment of MUI with conservative measures prior to surgical repair.^7,43

The International Consultation on Incontinence (ICI) constructed algorithms for urinary incontinence treatment and evaluation based on literature review and expert opinion.⁴³ The ICI is composed of a panel of world experts organized by the International Consultation on Urological Diseases and the World Health Organization. Their algorithms include initial management of uncomplicated incontinence for use by all clinicians (Figure 6-9)⁴³ and specialized management of complex incontinence intended for use by specialists (Figures 6-10 and 6-11).⁴³ The following is largely taken from their recommendations.

Evaluation of urinary incontinence begins with a careful history to distinguish between UUI, MUI, and SUI (Figure 6-9). The history helps differentiate more straightforward incontinence (Figure 6-9) from complex incontinence (Figure 6-10). Complex incontinence may be associated with prior radiation or surgery, recurrent urinary tract infections, or neurologic abnormalities (Figure 6-11). The history also includes a complete review of medications. For instance, diuretics contribute to urgency and frequency and change in dose or dosing intervals may improve symptoms.⁴⁴ In addition to the history, screening questionnaires assist in urinary incontinence diagnosis as most women will not admit to bothersome incontinence.⁴⁵ Questionnaires also help determine the level of bother experienced by patients due to their incontinence. Examples of such questionnaires are discussed in Chapter 4.