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A. Normal Urinary Bladder Function [2]navigator

  1. Detrusor muscle provides contractile force for emptying urinary bladder
  2. Detrusor muslce receives parasympathetic innervation from S2-S4 spinal nerves
  3. Internal urinary sphincter is derived from muscle layer beginning in urinary trigone
    1. This muscle is innervated by motor fibers from T11-L2 (sympathetic system)
    2. This is an involuntary muscle
  4. External urethral sphincter and perineal muscles are voluntary from pudendal nerves
  5. Normal adult bladder holds about 400mL (13.5 ounces) without distension
    1. Sensations of fullness are neurally transmitted above this volume
    2. Transmission to spinal cord via alpha myelinated bladder afferents
    3. Sacral spinal cord relaxes sphincters above this volume unless cortical override occurs
    4. The pontine micturition area is the initial cortical area involved
    5. Distension allows addition of another 100-200mL (up to 7 ounces additional)
    6. Typically, we respond to sensation in bladder at volumes of 200-300mL
  6. Pontine CNS Control of Micturition
    1. Pontine signals permit one to voluntarily delay bladder emptying
    2. Two main signals are involved: detrusor relaxation and bladder outlet constriction
    3. Detrusor relaxation mediated through ß2-adrenergic receptors in bladder body
    4. alpha1-adrenergic stimulation leads to bladder neck constriction
    5. Pelvic floor muscles also constrict, preventing urinary leakage
    6. Hypogastric and pudendal nerves carry these inhibitory signals
    7. These are sympathetic nerves, which also block parasympathetic pelvic signals
  7. Bladder Emptying
    1. In appropriate circumstance, CNS releases inhibitory signals, allows bladder emtyping
    2. Normal emptying involves coordination of multiple systems
    3. Relax bladder outlet, increase detrusor pressure, relax external sphincter
    4. Releaxation of urethra follwed by activation of spinal reflex pathway coordinated by pons
    5. Bladder contraction mediated primarily through acetylcholine (ACh)
    6. ACh binds muscarinic ACh receptors on detrusor muscle initiating contraction
    7. Of 5 types of muscarinic ACh receptors (M1-M5), M3 is most relevant in human bladder
    8. Activation of M3 stimulates phospholipase C and induces calcium mediated contraction
    9. ACh M2 receptor inhibits adenylate cyclase and reduces cAMP production
    10. ß3-adrenergic receptor activation by norepinephrine stimulates cAMP and relaxes bladder

B. Characteristics of Urinary Incontinence [2,6] navigator

  1. Defined as involuntary loss of urine which is objectively demonstrable and a social or hygenic problem [1]
  2. Affects up to ~70% of community dwelling women and 50% of nursing home residents
  3. Up to 50% of persons with urinary incontinence also have fecal incontinence [11]

C. Causes of Urinary Incontinencenavigator

  1. Urinary Incontinence Increases with Age [2]
    1. Younger persons nearly always have some specific, identifiable cause(s)
    2. Older persons often have multiple contributing factors
    3. Urinary tract infection (UTI) must be ruled out in all patients with incontinence
    4. Unopposed estrogen (ERT) and combined hormone replacement can increase risk of urinary incontinence in women who do not have it at baseline [15]
  2. Pregnancy [8]
    1. Overall incontinence prevalence is 10.1% in nulliparous women
    2. In women who have undergone Cesarean (C-) section, prevalence 15.9%
    3. In women with history of vaginal deliveries, prevalence is 21%
  3. Urethral Sphincter Incompetence
    1. Also called stress or urge incontinence
    2. Stress and urge incontinence are different conditions
    3. Mainly occurs in women
  4. Detrusor Instability - uncontrolled contractions of bladder
  5. Neurologic Dysfunction
    1. Upper Motor Neuron - spastic bladder (uncontrolled contractions)
    2. Lower Motor Neuron - flaccid bladder (cannot contract)
    3. Peripheral Neuropathy
    4. Spinal cord injuries above S2 lead to spontaneous urination when bladder fills
  6. Overflow Incontinence
    1. Anatomical Urethral Obstruction
    2. Neurological Damage
  7. Mechanical Abnormalities
    1. Extrophy of the Bladder
    2. Patent Urachus
    3. Ectopic Ureteral Openings
    4. Post-prostatic resection (TURP)
    5. Pelvic Surgery - including histerectomy (especially in age >60), sacrocolpopexy [12,19]
    6. Pelvic or Rectal Irradiation and fistula formation
    7. Crohn Disease with fistula formation
  8. Functional Incontinance - inability to reach toilet in time
  9. Obesity - may be independent risk factor for incontinence (~4X risk in fat versus thin women)
  10. Psychogenic Incontinance

D. Evaluation [1,5]navigator

  1. Patients are often shy about discussing these issues
  2. Important for physicians to raise symptoms with patients, directly ask about incontinence
  3. History and Description (essential in evaluation)
    1. Use to rule out transient causes and to help classify type of incontinence (see above)
    2. Does patient have intense urge to void, or does loss of urine occur spontaneously ?
    3. Do any actions (such as cough, stress, others) precipitate voiding ?
    4. Loss of small amounts of urine in spurts during coughing without urgency is usally stress incontinence and suggests sphincter insufficiency
    5. Spontaneous urge to void and loss of urine without stress suggests detrusor instability
    6. Does patient have constant sense of fullness ?
    7. Does patient have a sense of the approximate amount of urine lost ? (difficult to assess)
    8. Three urinary incontinence questions (3IQ): stress versus urge incontinence (see below)
    9. Careful review of pharmaceuticals (including non-prescription) is critical
  4. Rule out transient causes of incontinence [1]
    1. Mnemonic = "DIAPPERS"
    2. Delirium / Confusion
    3. Infection (urinary tract)
    4. Atrophic Urethritis / Vaginitis
    5. Pharmaceuticals - sedatives, diuretics, anticholinergics, narcotics, alpha-agonists
    6. Psychological
    7. Excess Urine Output - large fluid intake, diuretics, caffeine, theophylline, alcohol
    8. Restricted Mobility
    9. Stool Impaction / Constipation
  5. Physical Examination (highly recommended)
    1. Rectal Exam (not in children) - stool impaction, neurologic tone, enlarged prostate
    2. Attempt to palpate bladder
    3. Vaginal exam
    4. Simple neurological evaluation
    5. Urinalysis - especially to rule out urinary tract infection
    6. Presence of associated conditions such as heart failure, neuropathies, atrophic vaginitis
  6. Cough Stress Test - stress related leakage, particularly important in women
  7. Post-Void Residual Volume (PVR; highly recommended)
    1. If sphincter incontinance or hypotonic bladder is suspected, check PVR
    2. Patient voids into a receptacle (check urine dipstick)
    3. PVR is assessed by ultrasound (preferred) or by catheter
    4. If combined void and PVR volume are <200mL, fill bladder to better assess PVR
    5. PVR >100mL is abnormal in older persons (>50mL abnormal in younger)
  8. Recommended Tests [1]
    1. Renal function assessment
    2. Uroflowmetry and PVR measurement with ultrasound
    3. Urodynamic testing if elective incontinence surgery is being carried out
    4. Urinary tract imaging for specific indications
    5. Endoscopy (cystoscopy) to exclude other disorders (evaluate complex incontinence)
  9. Indications for Cystoscopy [6]
    1. Incontinence with hematuria or pyuria
    2. Irritative voiding symptoms (frequency, urgency) with urge incontinence in absence of reversible causes
    3. Bladder pain
    4. Recurrent cystitis
    5. Suburethral mass
    6. When urodynamic testing fails to duplicate symptoms of urinary incontinence
  10. The following tests are NOT recommended [1]:
    1. Urinary tract imaging without a specific indication
    2. Endoscopy without a specific indication
    3. Gas cystometry

E. Sphincter Incompetence [23] navigator

  1. Also called "stress" or "urge" incontinence"
    1. Strictly speaking, these are different conditions
    2. Stress incontinence is incontinence during exercise, or on sneezing or coughing
    3. Urge incontinence is incontinence preceded by an urgent desire to void
  2. Occurs due to ineffective internal sphincter (low urethral resistance)
    1. Cannot resist passage or urine under stress of increased intra-abdominal pressure
    2. Often occurs with physical activity, coughing or sneezing
  3. Common in postmenopausal multiparous women
    1. May affect up to 38% of of such women
    2. Often predisposes to other health problems in elderly women
    3. Overall incontinence rates increased 1.5-2.0X in any parous versus nulliparous women [8]
  4. Etiology
    1. Probably related to atrophy of female urethra in absence of estrogen
    2. ERT does not reduce, and is associated with increased, risk of any incontinence within one year in continent women [15]
    3. Hysterectomy increases risk of subsequent stree-urinary incontinenace surgery 2.4X [3]
    4. Common symptoms in women (~45%) after sacrocolpopexy for pelvic organ prolapse [19]
    5. May occur in men after prostate surgery (for prostate hyperplasia or carcinoma)
  5. Diagnosis
    1. Careful history with specific questions around stress and urge required [2]
    2. Use Simple 3IQ Test (see below) [7]
    3. Volumes of urine are generally small but if external sphincter is also damaged, voiding larger volumes may occur
    4. Urinalysis should be performed to rule out infection and other abnormalities
    5. Ultrasound - ultrasound evaluation of post-void volume
    6. Invasive urodynamics - catheter through urethra into bladder to test function of bladder by filling it with water
  6. Stress Versus Urge Incontinence: Three (3) Incontinence Questions (3IQ) [7]
    1. (1) During the last 3 months, have you leaked urine (even a small amount) ?
    2. (2) During the last 3 months, did you leak urine (all that apply):
    3. When you were performing some physical activity, such as coughing, sneezing, lifting or exercise?
      1. When you had the urge or the feeling that you needed to empty your bladder, but you could not get to the toilet fast enough?
      2. Without physical activity and without a sense of urgency?
    4. (3) During the last 3 months, did you leak urine most often:
    5. When you were performing some physical activity, such as coughing, sneezing, lifting or exercise?
      1. When you had the urge or the feeling that you needed to empty your bladder, but you could not get to the toilet fast enough?
      2. Without physical activity and without a sense of urgency?
      3. About equally as often with physical activity as with a sense of urgency?
    6. Response to question (3) above defines type of urinary incontinence:
    7. Most often with physical activity: stress only or stress predominant
      1. Most often with the urge to empty the bladder: urge only or urge predominant
      2. Whithout physical activity or sense of urgency: other cause or other mainly other cause
      3. About equally with physical activity and sense of urgency: mixed type
  7. Treatment [4,5,25]
    1. Behavioral Therapy
    2. Pelvic Floor Electrical Stimulation
    3. Clinic based programs more effective than self-help booklet [10]
    4. Impress Minigaurd - may be effective even for severe disease
    5. Reliance Urinary Control Insert
    6. Surgical elevation of urethrovesical angle in women
    7. Anticholinergic agents often effective but side effects are bothersome
    8. Norepinephrine reuptake inhibitor (duloxetine) approved for stress incontinence
    9. Pessaries or other mechanical devices which selectively support bladder neck
    10. No objective evidence that pessaries improve incontinence [6]
    11. Surgical treatment
  8. Behavioral Therapy [4,5]
    1. Behavioral therapy with pelvic floor electrical stimulation may be most effective
    2. Comprehensive behavioral training alone was not augmented by electrical stimulation [10]
    3. Behavioral therapy involves learning how to gain better control over micturition muscles
    4. May include charts or diaries to track urination schedules and episodes of incontinence
    5. Kegel exercises recommended to strengthen pelvic floor muscles to support bladder
  9. Pelvic Floor Electrical Stimulation
    1. Short pulses of electrical stimulation to strengthen pelvic floor muscles
    2. No benefit when added to comprehensive behavioral training [10]
  10. Anticholinergic Agents [4,5,13,17]
    1. These are muscarinic acetylcholine receptor (M1) blockers
    2. Oxybutinin and tolterodine are most commonly used; similar good efficacy [25]
    3. Side effects occur significantly less frequently with tolterodine than with oxybutynin
    4. Dry mouth, headache, constipation, dyspepsia, dry eyes are most common side effects
    5. Tolterodine (Detrol®) 1-2mg po bid or Detrol® LA (long acting) 2-4mg po qd [13]
    6. Oxybutinin (Ditropan®) 2.5-5mg po tid or long acting Ditropan XL® 5-30mg qd [13]
    7. Oxybutynin transdermal patch (Oxytrol®) 2x/wk (3.9mg per patch) [9]
    8. Patch form of oxybutynin may have less dry mouth but is probably not as effective as po
    9. Trospium (Sanctura®) 20mg po bid similar efficacy to other anticholinergics [14]
    10. Darifenacin (Enablex®) 7.5mg qd initially, up to 15mg qd after 2 weeks [16]
    11. Solifenacin (VESIcare®) 5mg po qd initially, up to 10mg qd if tolerated [16]
    12. Propanthine (Pro-banthine®), hyoscyamine (Cystospaz M®), falvoxate (Urispas®) also
    13. Dry mouth is main side effect of all anticholinergics, ~20% for long acting agents [14]
    14. These agents are only marginally more effective than placebo
  11. Other Agents
    1. Duloxetine (Cymbalta®, a norepinephrine reuptake inhibitor) improves stress incontinence but is not as effective as anticholinergic agents [25]
    2. Midodrine (alpha1-adrenergic agonist, ProAmantine®) 2.5-5.0mg po tid has some effect [4]
  12. Diapers (protective pads) are commonly needed
  13. Surgery is indicated when pharmacology and conservative measures have failed [2]
    1. Mainly for treatment of stress incontinence
    2. Sometimes for refractory detrusor overactivity and urinary tract fistulae
    3. Various procedures have been developed
    4. Options include retropubic urethroplexy (Burch) and pubovaginal sling, others
    5. Burch culposuspension added to sacrocolpopexy reduces stress urinary incontinence symptoms to ~24% [19]
    6. Autologous fascial sling superior efficacy (47% versus 38%) with greater side effects compared with Burch procedure [21]
  14. Autologous myoblasts/fibroblast injections are superior to collagen for treatment of stress urinary incontinence in women in early studies [22]

F. Detrusor Instability [18] navigator

  1. Also called "overactive bladder", detrusor overactivity, detrusor hyper-reflexia
  2. Bladder has uncontrollable contractions
  3. Underlying neurological causes are present in most cases
  4. Characteristics
    1. Urinary urgency with or without urge incontinence, voiding at least 8 times in 24 hours
    2. Unpredictable involuntary voiding
    3. Generally >160mL of urine per event
    4. Often wakes with nonsuppressible urge to void at least twice nightly
    5. Often small amounts of leakage occur even after voiding
  5. Underlying Conditions in Younger Persons
    1. Usually due to damaged inhibitory neural pathways
    2. Spinal Cord Injury
    3. Multiple Sclerosis
  6. Underlying Conditions in Older Persons
    1. Stroke
    2. Alzheimer's Disease
    3. Cerebral Neoplasm
    4. Intermittant Pressure Hydrocephalus
    5. Often associated with benign prostatic hyperplasia (BPH)
    6. An underlying cause is often not found in elderly
  7. Other Causes
    1. Bladder or Pelvic Infection
    2. Bladder or Pelvic Mass (Neoplasm, Abscess, Hemorrhage)
    3. Fecal impaction
    4. Uterine Prolapse
    5. Prostatic Hypertrophy
  8. Treatment [4,5]
    1. Underlying causes / contributors
    2. Anticholinergic Agents: oxybutinin or tolterodine most commonly (dosed as above) [13,16]
    3. In men with BPH and overactive bladder, combination of tolterodine extended release with tamsulosin (an alpha1-adrenergic blocker) superior to either alone or placebo [20]
    4. Dicyclomine 10-30mg po divided daily also used
    5. Calcium channel blocking agents: nifedipine or diltiazem also stabilize muscle
    6. Imipramine 25mg po qhs is also often effective
    7. Bladder retraining may be attempted (particulalry with daytime symptoms)
    8. Diapers (protective pads) are commonly needed
    9. Self-catheterization may be required

G. Overflow Incontinencenavigator

  1. Due to Outflow Obstruction and Bladder Hyperinflation
    1. Most commonly due to anatomic bladder obstruction
    2. Functional Obstruction - spinal and/or peripheral nerve damage
    3. Detrusor hyperactivity often accompanies impaired contractility
  2. Anatomic Bladder Obstruction
    1. Benign Prostatic Hyperplasia (BPH) - most common cause in men
    2. Urethral Strictures - more common in women after frequent urinary tract infections
    3. Pelvic Mass
  3. Functional Outflow Obstruction
    1. Spinal Nerve Damage - destrusor and extgernal sphincter contract dyssynergistically
    2. Peripheral Neuropathy with Hypotonic Bladder - diabetes, Guillain-Barre, toxins
  4. Clinical Findings
    1. Dilated, palpable bladder
    2. Enlarged prostate in BPH
    3. Presence of underlying conditions
  5. Treatment
    1. Anatomic Obstructions are treated surgically
    2. Underlying disorders are treated
    3. Hypotonic bladder - may respond to bethanechol (Urocholine®) 25mg po bid-qid
  6. ERT is associated with increased risk of any incontinence within 1 year in continent women [15]

References navigator

  1. First International Consultation of Incontinence. 2000. Lancet. 355(9221):2153 abstract
  2. Norton P and Brubaker L. 2006. Lancet. 367(9504):57 abstract
  3. Altman D, Granath F, Cnottingius S, Falconer C. 2007. Lancet. 370(9597):1494 abstract
  4. Holroyd-Leduc JM and Straus SE. 2004. JAMA. 291(8):986 abstract
  5. Holroyd-Leduc JM and Straus SE. 2004. JAMA. 291(8):998
  6. Morantz C. 2005. Am Fam Phys. 72(1):175
  7. Brown JS, Bradley CS, Subak LL, et al. 2006. Ann Intern Med. 144(10):715 abstract
  8. Rortveit G, Daltveit AK, Hannestad YS, Hunskaar S. 2003. NEJM. 348(10):900 abstract
  9. Oxybutynin Transdermal (Oxytrol). 2003. Med Let. 45(1156):38 abstract
  10. Goode PS, Burgio KL, Locher JL, et al. 2003. JAMA. 290(3):345 abstract
  11. Tariq SH, Morley JE, Prather CM. 2003. Am J Med. 115(3):217 abstract
  12. Brown JS, Sawaya G, Thom DH, Grady D. 2000. Lancet. 356(9229):535 abstract
  13. Detrol LA and Ditropan XL. 2001. Med Let. 43(1101):28 abstract
  14. Trospium. 2004. 46(1188):63 abstract
  15. Hendrix SL, Cochrane BB, Nygaard IE, et al. 2005. JAMA. 293(8):935 abstract
  16. Solifenacin and Darifenacin. 2005. Med Let. 47(1204):23 abstract
  17. Tolterodine (Detrol). 1998. Med Let. 40:101 abstract
  18. Ouslander JG. 2004. NEJM. 350(8):786 abstract
  19. Brubaker L, Cundiff GW, Fine P, et al. 2006. NEJM. 354(15):1557 abstract
  20. Kaplan SA, Roehrborn CG, Rovner ES, et al. 2006. JAMA. 296(19):2319 abstract
  21. Albo ME, Richter HE, Brubaker L, et al. 2007. NEJM. 356(21):2143 abstract
  22. Strasser H, Marksteiner R, Margreiter E, et al. 2007. Lancet. 369(9580):2179 abstract
  23. Rogers RG. 2008. NEJM. 358(10:1029 abstract
  24. Landefeld CS, Bowers BJ, Feld AD, et al. 2008. Ann Intern Med. 148(6):449 abstract
  25. Shamliyan TA, Kane RL, Wyman J, Wilt TJ. 2008. Ann Intern Med. 148(6):459 abstract