Pathophysiolo gy of Urinar y Incontinence, Voiding Dysfunction, and Overactive Bladder David D. Rahn, MD*, Shayzreen M. Roshanravan, MD KEYWORDS Detrusor overactivity Instability Urinary stress incontinence Neuroanatomy Neurophysiology
DEFINITIONS,TERMINOLOGY
Pelvic floor dysfunction may include problems of urine storage and evacuation, inadequate support of the pelvic viscera, colorectal/anal disorders, and acute or chronic pelvic pain. When considering just the disorders of the lower urinary tract, there is an abundance of terms describing the various symptoms and suspected etiologies of these storage and evacuation problems; miscommunication and confusion may result. The International Continence Society has attempted to standardize several definitions based on patients’ symptoms to facilitate more effective communication between physicians, patients, and researchers.1 These urinary disorders may be divided into three categories: problems with storage, voiding, and postmicturition. Among the storage symptoms, urinary incontinence is broadly defined as ‘‘the complaint of any involuntary leakage of urine.’’ More specifically, stress urinary incontinence is ‘‘involuntary leakage on effort or exertion, or on sneezing or coughing.’’ Urinary urgency is ‘‘the complaint of a sudden compelling desire to pass urine which is difficult to defer’’ and urgency incontinence is ‘‘the complaint of involuntary leakage accompanied by or immediately preceded by urgency.’’1,2 Taken together, overactive bladder syndrome is ‘‘urgency, with or without urgency incontinence usually with increased daytime frequency and nocturia.’’2 Voiding symptoms include problems with slow urinary stream, splitting or spraying, intermittency or hesitancy with the urine flow, or straining to void. Postmicturition symptoms include feelings of incomplete emptying and postmicturition dribble. Although all of these labels may help characterize patients by their predominant
Division of Female Pelvic Medicine and Reconstructive Surgery, Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9032, USA * Corresponding author. E-mail address: david.rahn@utsouthwestern.edu (D.D. Rahn). Obstet Gynecol Clin N Am 36 (2009) 463–474 doi:10.1016/j.ogc.2009.08.012 0889-8545/09/$ – see front matter ª 2009 Elsevier Inc. All rights reserved.
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symptoms, they do not provide insight into the degree to which symptoms bother patients nor the etiology of these symptoms. This article presents a simplified explanation of the mechanics of urine storage and emptying, establishing a framework to understand how different physiologic and pathologic states may contribute to the disorders mentioned earlier. PHYSIOLOGIC NEUROANATOMY OF URINE STORAGE AND EVACUATION
The anatomy of the lower urinary tract is closely related to its function of storage and evacuation of urine. The bladder remains relaxed during the storage phase and contracts during the evacuation phase. The urethra acts in synchrony with the bladder but has reciprocal actions: contracting during storage and relaxing during evacuation. The coordinated function of this system depends on complex interactions between the nervous system and the lower urinary tract anatomy. Anatomy: Bladder
The urinary bladder is a muscular organ that consists of coarse bundles of smooth muscle known as the detrusor muscle (Fig. 1). The bladder is lined by transitional epithelium, which merges with the squamous epithelium of the urethra. Approximately at the level of the ureteral orifices, the bladder can be divided into two parts: a body (or dome) and a base. The base of the bladder includes the vesical trigone, which is bounded by the two ureteral orifices and the internal urethral opening. An important distinction between the dome and the base is the type of neurotransmitter receptor that predominates (see Fig. 1). At the dome, beta-adrenergic and cholinergic receptors predominate, whereas alpha-adrenergic receptors predominate at the base and the proximal urethra. The primary cholinergic (muscarinic) receptor subtypes in the human bladder are M2 and M3. Although there are more M2 receptors, the M3
Fig. 1. Urinary bladder. a, alpha adrenergic receptors; b, beta adrenergic; M, muscarinic (cholinergic). (Courtesy of Lindsay Oksenberg, Dallas, TX)
Pathophysiology of Lower Urinary Tract Dysfunction
receptors predominate in the mediation of detrusor contraction.3 The vesical neck is that area of the bladder where the urethral lumen passes through the musculature of the bladder base.4 Anatomy: Urethra
In women, the urethra is a complex 3 to 4 cm structure that extends from the bladder to the external urethral opening (Fig. 2A, B). Surrounding the mucosal lining of the urethra is a submucosal layer that contains a prominent vascular plexus. This plexus is thought to contribute to the watertight closure of the urethral lumen. Adjacent to the submucosal layer lie two layers of smooth muscle: a well-developed inner longitudinal and a poorly defined outer circular layer. These smooth muscle layers are thought to assist with constriction and opening of the urethral lumen. The most external layer of the urethral wall consists of the striated urogenital sphincter muscles (see Fig. 2B).5,6 This complex consists of the sphincter urethrae and two strap like bands of muscle, the urethrovaginal sphincter and compressor urethrae muscles (Fig. 3).7,8 The sphincter urethrae surrounds the proximal region of the urethra. This muscle is an integral part of the urethral wall and its fibers are oriented in a circular fashion. The compressor urethrae and urethrovaginal sphincter muscles arch over the ventral surface of the urethra and are found just superior to the perineal membrane (see Fig. 3). Peripheral nervous system
Understanding the normal physiologic function of the lower urinary tract requires a basic understanding of its peripheral innervation.9 The peripheral nervous system has a somatic and an autonomic component. The somatic component innervates skeletal or striated muscle, whereas the autonomic component innervates smooth muscle, cardiac muscle, and glands. In the lower urinary tract, somatic nerves innervate the muscles that comprise the striated urogenital sphincter complex. Autonomic nerves supply the detrusor muscle of the bladder and smooth muscle of the urethra (Fig. 4).
Fig. 2. Urethral anatomy. (A) Isolated urethral anatomy in cross section. Urethral coaptation results in part from filling of the rich subepithelial vascular plexus. (B) Vesical neck and urethral anatomy. (From Wai CY.Urinary incontinence. In: Schorge JO, Schaffer JI, Halvorson LM, et al, editors. Williams Gynecology, 1st edition. New York: McGraw Hill Medical; 2008. p. 517; with permission.) (Courtesy of Lindsay Oksenberg, Dallas, TX).
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Fig. 3. Striated urogenital sphincter anatomy. With the perineal membrane removed or reflected, one encounters the three component muscles of the striated urogenital sphincter. (Courtesy of Lindsay Oksenberg, Dallas, Texas).
The autonomic nervous system is further divided into sympathetic and parasympathetic divisions. Fibers arising from the intermediolateral gray column of the tenth thoracic and first two lumbar spinal cord segments form the pelvic sympathetic division. The pelvic parasympathetic division consists of fibers arising from the intermediolateral cell columns of the second through fourth sacral cord segments. Autonomic fibers that supply the pelvic viscera course in the superior and inferior hypogastric plexuses (Fig. 5). The superior hypogastric plexus primarily contains sympathetic fibers from the T10 to L2 cord segments and terminates by dividing into right and left hypogastric nerves. The inferior hypogastric plexus, also known as the pelvic plexus, is formed by visceral efferents from S2 to S4, which provide
Fig. 4. Peripheral nervous system innervation of the lower urinary tract. (Courtesy of Lindsay Oksenberg, Dallas, TX).
Pathophysiology of Lower Urinary Tract Dysfunction
Fig. 5. The pelvic plexus. (Courtesy of Lindsay Oksenberg, Dallas, TX).
the parasympathetic component by way of the pelvic nerves. The lateral extensions of the superior hypogastric plexus, the hypogastric nerves and rami from the sacral portion of the sympathetic chain, contribute the sympathetic component to the pelvic plexus. The pelvic plexus divides into three portions according to the course and distribution of its fibers: the middle rectal plexus, uterovaginal plexus (or Frankenhauser’s ganglion), and vesical plexus (see Fig. 5).10 The somatic component of the peripheral nervous system that is relevant to lower urinary tract function takes origin from Onuf’s somatic nucleus (Fig. 6). Onuf’s nucleus, located in the ventral horn of the gray matter of S2 through S4, contains the neuronal cell bodies of the fibers that supply the striated urogenital sphincter complex. The urethrovaginal sphincter and compressor urethrae are innervated by the perineal branch of the pudendal nerve. The sphincter urethrae are variably innervated by somatic efferents that travel in the pelvic nerves. Neurophysiology
Normal voiding function requires higher cortical areas of the brain, which allow for voluntary control over the primitive autonomic reflex arcs found within the sacral spinal cord. This central coordination of micturition largely occurs in the pontine micturition center. The parietal lobes and thalamus receive and coordinate the bladder detrusor afferent stimuli, whereas the frontal lobes and basal ganglia modulate with inhibitory signals. There is also peripheral coordination that occurs in the sacral micturition center (S2–4). Precise knowledge of the neural pathways involved in voiding remains controversial; the concepts presented here represent a summary of the major pathways. Urine storage depends predominantly on sympathetic neural activity. During storage, bladder distention results in afferent input from sensory neurons located in
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Fig. 6. Onuf’s somatic nucleus. (Courtesy of Lindsay Oksenberg, Dallas, TX).
the bladder wall. This leads to activation of urethral motor neurons in Onuf’s nucleus, which results in contraction of the striated urogenital sphincter muscles by way of the pudendal nerve. Simultaneously, activation of the spinal sympathetic reflex (T11–L2) by way of the hypogastric nerves results in alpha-adrenergic contraction of urethral smooth muscle with increased tone at the vesical neck and inhibition of parasympathetic transmission, which inhibits detrusor contraction.11 The net effect is that urethral pressure remains greater than detrusor pressure, facilitating storage (Fig. 7). When there are increases in abdominal pressure, a fascial and muscular urethral support hammock compresses the urethra to help maintain continence12; this is also accomplished when the pelvic muscles are contracted. Voiding is largely a parasympathetic event. This begins with efferent impulses from the pontine micturition center, which results in inhibition of somatic fibers in Onuf’s nucleus and voluntary relaxation of the striated urogenital sphincter muscles. These efferent impulses also result in preganglionic sympathetic inhibition with opening of the vesical neck and parasympathetic stimulation, which results in detrusor muscarinic contraction. The net result is relaxation of the striated urogenital sphincter complex causing decreased urethral pressure, followed almost immediately by detrusor contraction and voiding (Fig. 8). NEUROGENIC CAUSES OF URINE STORAGE AND EVACUATION DYSFUNCTION
Voluntary control of the micturition reflex is mediated by connections between the frontal cerebral cortex and the pons. Voluntary control of the striated urogenital sphincter muscles is through the corticospinal pathway connecting the frontal cortex with Onuf’s somatic nucleus. Disruption of these neural pathways can result in dysfunctional storage and voiding patterns. Lesions in the cortical centers of the brain can result in urge incontinence, enuresis, and urethral spasm. Patients may be unaware of their incontinence. Patients suffering from stroke, Alzheimer disease, multi-infarct dementia, other dementias, Parkinson
Pathophysiology of Lower Urinary Tract Dysfunction
Fig. 7. Urine storage. Bladder distention from filling leads to alpha-adrenergic contraction of the urethral smooth muscle and increased tone at the vesical neck (T11-L2 spinal sympathetic reflex); activation of urethral motor neurons in Onuf’s nucleus with contraction of striated urogenital sphincter muscles (by way of the pudendal nerve); and inhibited parasympathetic transmission with decreased detrusor pressure. a, alpha adrenergic receptors; b, beta adrenergic; M, muscarinic (cholinergic). (Courtesy of Lindsay Oksenberg, Dallas, TX).
Fig. 8. Urine evacuation. Efferent impulses from the pontine micturition center cause inhibition of somatic fibers in Onuf’s nucleus with voluntary relaxation of the striated urogenital sphincter muscles; preganglionic sympathetic inhibition with relaxation at the vesical neck; and parasympathetic stimulation with detrusor muscle contraction. a, alpha adrenergic receptors; M, muscarinic (cholinergic). (Courtesy of Lindsay Oksenberg, Dallas, Texas).
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disease, or multiple sclerosis with suprapontine lesions may experience involuntary detrusor contractions, which occur in synchrony with relaxation of the urethra. These contractions can result in neurogenic detrusor overactivity with urgency/frequency and urgency incontinence. High spinal cord or upper motor neuron lesions can also result in neurogenic detrusor overactivity. However, the detrusor contractions are not synchronized with urethral relaxation, resulting in detrusor-sphincter dyssynergia where patients can also have urinary retention. This dyssynergia can be seen with acute spinal cord trauma, cervical or lumbar stenosis, disc herniation, or chronic conditions involving the spinal cord, such as multiple sclerosis. Lastly, lower motor neuron lesions, as seen with injury to the peripheral nervous system, may result in reduced contraction of the detrusor muscle. This may manifest as overflow incontinence. In developed countries, the most common cause of peripheral neuropathy is diabetes. Injury to the pelvic plexus can be seen with resection surgery, such as radical hysterectomy or rectal surgery. In these cases, parasympathetic innervation is mainly affected. MUSCULAR CAUSES OF URINE STORAGE AND EVACUATION DYSFUNCTION
The detrusor muscle’s functional ability to contract appropriately may be altered as a result of aging, atrophy, trauma, or decreased muscular innervation. The smooth muscle contractions of the detrusor require several interacting biochemical pathways to raise intracellular calcium levels; these include adenosine triphosphate (ATP) phosphorylation, protein kinases, and potassium and calcium channels. Alterations in any of these pathways may result in inappropriate contractions or loss in contractility.13,14 Studies have demonstrated that women who have detrusor overactivity have structural changes in their bladder walls at the tissue and cellular levels. Electron microscopy examining the ultrastructural anatomy of detrusor cells suggests that patients who have overactivity have an abnormal number of intercellular connections used for communication between smooth muscle cells, which may facilitate the generation of inappropriate detrusor contractions.15 At a light microscopic level, overactive bladder tissue has demonstrated increases in elastin, collagen, and segments of denervated muscle.16 STRESS URINARY INCONTINENCE
Theories regarding the maintenance of urinary continence during increases in intraabdominal pressure involve concepts of pressure transmission, anatomic support, and urethral integrity. Most simply, continence during these times of physical stress requires anatomic urethral support and urethral integrity. Ideal support requires intact and healthy (1) ligaments along the lateral aspects of the urethra, termed the pubourethral ligaments; (2) anterior vaginal wall and its lateral fascial condensation; (3) arcus tendinous fascia pelvis; and (4) levator ani muscles. Collectively, this support provides a firm backboard against which the urethra is supported during increases in intraabdominal pressure. With the loss of this support, downward forces, such as from a cough, sneeze, or laugh, are not countered as they should be; the urethra funnels at the urethrovaginal junction; the urethra becomes more patent and has a reduced closing pressure; and continence is lost (Fig. 9).17 Mechanical closure/integrity of the urethra is also necessary to prevent stress urinary incontinence. This closure/integrity requires mucosal surface coaptation and intact viscoelastic properties of the urethral epithelium, a healthy underlying urethral vascular plexus, and contraction of the surrounding musculature (see Fig. 2). Defects
Pathophysiology of Lower Urinary Tract Dysfunction
Fig. 9. Stress urinary incontinence: the pressure-transmission theory. (From Wai CY. Urinary incontinence. In: Schorge JO, Schaffer JI, Halvorson LM, et al, editors. Williams Gynecology. 1st edition. New York: McGraw Hill Medical; 2008. p. 518; with permission.)
in any of these components may contribute to stress incontinence by way of ‘‘intrinsic sphincter deficiency.’’12 Possible etiologies of such defects include prior retropubic surgery with denervation or scarring of the urethra and supporting tissue, prior pelvic radiotherapy, hypoestrogenism, diabetic neuropathy, and other degenerative neuronal diseases. Childbirth and associated trauma can physically disrupt the musculature of the urogenital sphincter or its supportive fascia or muscles (levator ani) or may cause nerve damage with immediate or delayed stress urinary incontinence.
COMORBID CONDITIONS AND OTHER FACTORS AFFECTING URINE STORAGE AND EVACUATION
Urinary incontinence often reflects multidimensional and multiple impairments. Besides requiring intact micturition physiology (including the lower urinary tract, pelvic, and neurologic components described earlier), continence depends on an intact functional ability to toilet oneself. Several medical conditions and pharmacologic agents can negatively impact this ability. One pneumonic designed to highlight these potentially reversible or transient contributors to urinary incontinence is DIAPPERS: Dementia/delirium, Infection, Atrophic vaginitis, Psychological, Pharmacologic, Endocrine, Restricted mobility, and Stool impaction.18 Continence requires the cognitive ability to recognize and react appropriately to the sensation of a full bladder, motivation to maintain dryness, sufficient mobility and manual dexterity, and ready access to toilet facilities. Patients who have dementia or significant psychological impairments often do not have this necessary cognitive ability or motivation for maintenance of continence, and women who have severe physical handicaps or restricted mobility may simply not have time to reach the toilet, especially in the setting of urinary urgency/overactive bladder. Urinary tract infections cause inflammation of the bladder mucosa. Sensory afferent activity increases with this inflammation, which contributes to an overactive bladder. Similarly, estrogen deficiency may lead to atrophic vaginitis and urethritis with increased local irritation and a greater risk of urinary tract infection and overactive bladder. Topical estrogen may ameliorate symptoms and infections should be treated before other incontinence interventions are considered.3
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472 Table 1 Medications that may contribute to voiding dysfunction Medication
Examples
Mechanism
Effect
Alcohol
Beer, wine, liquor
Diuretic effect, sedation, immobility
Polyuria, frequency
Alpha-adrenergic agonist
Decongestants, diet pills
IUS contraction
Urinary retention
Alpha-adrenergic blockers
Prazosin, terazosin, doxazosin
IUS relaxation
Urinary leakage
Inhibit bladder contraction, sedation, fecal impaction
Urinary retention or functional incontinence
Anticholinergic agents
Antihistamines
Antipsychotics
Antiparkinsonians
Skeletal muscle relaxants Tricyclic antidepressants
Miscellaneous
Diphenhydramine, scopolamine, dimenhydrinate Thioridazine, chlorpromazine, haloperidol Trihexyphenidyl, benztropine mesylate Orphenadrine, cyclobenzaprine Amitriptyline, imipramine, nortriptyline, doxepin Dicyclomine, disopyramide
Angiotensinconverting enzyme inhibitors
Enalapril, captopril, lisinopril, losartan
Chronic cough
Urinary leakage
Calcium-channel blockers
Nifedipine, nicardipine, isradipine, felodipine
Relaxes bladder, fluid retention
Urinary retention, nocturnal diuresis
Cyclooxygenase-2 selective NSAID
Celecoxib
Fluid retention
Nocturnal diuresis
Diuretics
Caffeine, HCTZ, furosemide, bumetanide, acetazolamide, spironolactone
Increases urinary frequency, urgency
Polyuria
Narcotic analgesics
Opiates
Relaxes bladder, fecal impaction, sedation
Urinary retention and/ or functional incontinence
Thiazolidinediones
Rosiglitazone, pioglitazone, troglitazone
Fluid retention
Nocturnal diuresis
Abbreviations: HCTZ, hydrochlorothiazide; IUS, internal urethral sphincter; NSAID, nonsteroidal antiinflammatory drug. From Wai CY. Urinary incontinence. In: Schorge JO, Schaffer JI, Halvorson LM, et al, editors. Williams Gynecology. 1st edition. New York: McGraw Hill Medical; 2008. p. 521; with permission.
Pathophysiology of Lower Urinary Tract Dysfunction
Although incontinence should not be viewed as a normal consequence of aging, there are several physiologic changes that occur in the lower urinary tract with aging that may predispose one to incontinence, overactive bladder, or other voiding difficulties. First, the prevalence of involuntary detrusor contractions increases with aging, with detrusor overactivity being found in 21% of healthy, continent, communitydwelling elderly.19 Total bladder capacity may diminish and the ability to postpone voiding decreases, leading to urinary frequency. Meanwhile, urinary flow rate decreases in older men and women likely because of an age-related decrease in detrusor contractility.20 In women, postmenopausal decrease in estrogen levels results in atrophy of the urethral mucosal seal, loss of compliance, and bladder irritation, which may predispose to stress and urgency urinary incontinence. Age-related changes in renal filtration rate and alterations in diurnal levels of antidiuretic hormone and atrial natriuretic factor shift the diurnal pattern of fluid excretion toward increased volume of urine excreted later in the day.21 Comorbid conditions, such as congestive heart failure, hypothyroidism, venous insufficiency, and the effects of certain medications all contribute to peripheral edema leading to urinary frequency and nocturia when a patient is supine. Diabetes mellitus can lead to osmotic diuresis and polyuria when there is poor glucose control. Polydipsia from diabetes insipidus or excessive intake of caffeine or alcohol can also lead to polyuria/urinary frequency. Similarly, abnormalities of arginine vasopressin with its impaired secretion or action may cause polyuria and nocturia; these carefully selected patients may benefit from desmopressin therapy.3 Finally, stool impaction resulting from poor bowel habits and constipation can contribute to overactive bladder symptoms, perhaps from local irritation or direct compression against the bladder wall. As alluded to earlier, there are many medications that may cause or worsen urinary incontinence or other forms of voiding dysfunction. This dysfunction occurs through changes in rate of urine production, the integrity of the sympathetic and parasympathetic nervous systems, and cognition. It is important to note patients’ use of diuretics, anticholinergic medications, alcohol, psychotropic medications, narcotics, alpha agonists or antagonists, beta mimetics, or calcium channel blockers (see Table 1). SUMMARY
The coordinated function of the lower urinary tract system depends on the normal and complex interactions between the nervous system and the lower urinary tract anatomy. A thorough understanding of these components and their interactions is essential to properly diagnose and manage lower urinary tract dysfunction. ACKNOWLEDGMENTS
The authors thank Ms. Lindsay Oksenberg, medical illustrator, University of Texas Southwestern Office of Medical Education, for use of the many illustrations demonstrating lower urinary tract neurophysiology. REFERENCES
1. Abrams P, Cardozo L, Fall M, et al. The standardisation of terminology of lower urinary tract function: report from the Standardisation Sub-committee of the International Continence Society. Am J Obstet Gynecol 2002;187(1):116–26. 2. Abrams P, Artibani W, Cardozo L, et al. Reviewing the ICS 2002 terminology report: the ongoing debate. Neurourol Urodyn 2009;28(4):287.
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3. Ouslander JG. Management of overactive bladder. N Engl J Med 2004;350(8): 786–99. 4. DeLancey JO. Correlative study of paraurethral anatomy. Obstet Gynecol 1986; 68(1):9–17. 5. Berkow SG. The corpus spongiosum of the urethra: its possible role in urinary control and stress incontinence in women. Am J Obstet Gynecol 1953;65(2): 346–51. 6. Rud T, Andersson KE, Asmussen M, et al. Factors maintaining the intraurethral pressure in women. Invest Urol 1980;17(4):343–7. 7. Gosling JA. Structure of the lower urinary tract and pelvic floor. Clin Obstet Gynaecol 1985;12(2):285–94. 8. Oelrich TM. The striated urogenital sphincter muscle in the female. Anat Rec 1983;205(2):223–32. 9. Benson JT, Walters MD. Neurophysiology and pharmacology of the lower urinary tract. In: Walters MD, Karram MM, editors. Urogynecology and reconstructive pelvic surgery. 3rd edition. Philadelphia: Mosby Elsevier; 2007. p. 31–43. 10. Ashley FL, Anson BJ. The pelvic autonomic nerves in the male. Surg Gynecol Obstet 1946;82:598–608. 11. Van Arsdalen K, Wein A. Physiology of micturition and continence. In: Krane RJ, Siroky MB, editors. Clinical neuro-Urology. 2nd edition. Boston: Little, Brown; 1995. p. 25. 12. DeLancey JOL. Structural aspects of the extrinsic continence mechanism. Obstet Gynecol 1988;72:296–301. 13. Blakeman P, Hilton P. Cellular and molecular biology in urogynaecology. Curr Opin Obstet Gynaecol 1996;8(5):357–60. 14. Levin RM, Levin SS, Wein AJ. Etiology of incontinence: a review and hypothesis. Scand J Urol Nephrol Suppl 1996;179:15–25. 15. Elbadawi A, Yalla SV, Resnick NM. Structural basis of geriatric voiding dysfunction. III. Detrusor overactivity. J Urol 1993;150(5 Pt 2):1668–80. 16. Brading AF. A myogenic basis for the overactive bladder. Urology 1997;50(Suppl 6A):57–67. 17. Wai CY. Urinary incontinence. In: Schorge JO, Schaffer JI, Halvorson LM, et al, editors. Williams gynecology. 1st edition. New York: McGraw Hill Medical; 2008. p. 517–8. 18. Swift SE, Bent AE. Basic evaluation of the incontinent female patient. In: Bent AE, Cundiff GW, Swift SE, editors. Ostergard’s urogynecology and pelvic floor dysfunction. 6th edition. Philadelphia: Lippincott Williams and Wilkins; 2008. p. 67. 19. Resnick NM, Elbadawi A, Yalla SV. Age and the lower urinary tract: what is normal? Neurourol Urodyn 1995;14:577. 20. Resnick NM. Voiding dysfunction in the elderly. In: Yalla SV, McGuire EJ, Elbadawi A, et al, editors. Neurourology and urodynamics: principles and practice. New York: MacMillan; 1984. p. 303. 21. Kirkland JL, Lye M, Levy DW, et al. Patterns of urine flow and excretion in healthy elderly people. Br Med J 1983;287:1665–7.