1. Urgency Frequency Syndrome
Hann-Chorng Kuo
Department of Urology
Buddhist Tzu Chi General Hospital Hualien

2. Lower Urinary Tract Symptoms
Storage symptoms --
Frequency, urgency, urge incontinence, nocturia, suprapubic pain
Empty symptoms --
Hesitancy, intermittency, dysuria, poor stream, terminal dribble, residual sensation, micturition pain

3. The Urge Syndrome
Sensory urgency – hypersensitivity of bladder or urethra or both, which causes
-- a constant desire to void which is unrelieved by voiding
-- a desire to void at a low bladder volume
Motor urgency – occurrence of involuntary detrusor contractions which make patients urge to void and/or urine leakage

4. Frequency & Polyuria (Pollakisuria)
A number of patients may have large daily urine output >2800ml/day
Polydipsia, high water intake
Frequency with voided volume >350ml is physiologically normal
Should check metabolic status (DM, azotemia, hyperlipidemia, etc.) or diuretics

5. Sensory Urgency & Frequency
Reduced capacity of first desire (<150mL) or urgency (<350mL) subjectively
Absence of detrusor instability
Absence of urinary tract infection
The incidence of sensory urgency has been estimated 6%, compared with an incidence of 31% for detrusor instability

6. Known Causes of Sensory urgency freqency
Urinary tract infection
Lower ureteral stone or bladder stone
Bladder tumor
Irradiation cystitis
Interstitial cystitis
Chonic cystitis and reduced capacity
Foreign body or bladder injury

7. Etiology of Idiopathic Urgency Frequency
Psychological factors
Urothelial leak syndrome
Reduced bladder compliance
Diuresis
Learned habit
Detrusor instability
Occult neuropathy

8. Sensory Urgency A Psychosomatic Complaint ?
Bladder retraining is effective in treating sensory urgency
Relaxation training, biofeedback, hypnosis, acupuncture have a 85% initial response, but relapse rate is 50%
Cognitive factor to maintain high stress and arousal levels, increase vigilance concerning bladder sensation and fullness

9. Psychological Social & Psychiatrical Factors
High level of distress
High level of anxiety
Symptoms may worsen in relation to work or stress
Belief of relationship with disease – uremia, infection, cancer
Overestimate the significance of symptoms

10. Sensory Urgency Frequency
A disease of exclusion
Acute symptoms and chronic symptoms?
Related to empty symptoms or not?
Related to painful syndrome (painful bladder, painful perineum, urethral pain)?
Intermittent? Persistent? Waxing & waning?
Related to urge or stress incontinence?

11. Diagnostic Work-up Urinalysis Uroflowmetry & residual urine amount
Voiding diary – 3 days
KUB or Cystoscopy
Ultrasound of bladder and urethra
Cystometry & sphincter EMG
Pressure flow study or videourodynamics

12. Pathophysiology of LUTS in 256 Taiwanese Women
Normal bladder and urethra 46
Hypersensitive bladder 102
Detrusor instability 44
Low detrusor contractility 77
Poor relaxation of urethral sphincter 76
Genuine stress urinary incontinence 49
Bladder outlet obstruction 21

13. Urethral sensitivity An etiology of urgency frequency?
Increased urethral sensitivity was found in reduced bladder capacity and in women with normal CMG who complain of frequency urgency & dysuria
A higher incidence of bladder neck incompetence in patients with urgency frequency than the controls
Pelvic floor exercises and bladder neck suspension improves urgency frequency symptoms

14. Bladder Neck Incompetence in Urgency Frequency Syndromes
PVL(cm)
PVS(degrees)
Resting
Straining
Increment
Bladder neck
incompetence 43
(55.1%)
1.99±0.40
2.07±0.46
0.08±0.22
25.7±21.8
51.2±30.4
25.5±18.9
competence 35
(44.9%)
2.12±0.37
2.14±0.39
0.03±0.16
9.4±9.5
20.4±15.0
11.0±11.7
Statistics NS
P<0.005

15. Ultrasound of Bladder neck incompetence in urgency frequency

16. Bladder Neck Decsent & Incompetence before Pelvic Floor exercises

17. Improved Bladder neck Incompetence after Pelvic Floor exercises

18. Detrusor Instability as an etiology of urgency frequency
Minute detrusor contraction occur in the normal bladder – C-fiber dominates?
Increased perception of bladder fullness during diuresis
No significant difference in perception of bladder fullness between sensory urgency and detrusor instability
Similar clinical efficacy of oxybutynin in treating sensory urgency (62.5%) and DI (60.4%)

19. Increased amplitude of detrusor contractions in bladder filling

20. Sensory nerves of bladder
Dual sensory innervation of mammalian bladder
Myelinated A-delta fibers – mediate stretch and micturition reflex
Unmyelinated C-fibers (capsaicin sensitive sensory fibers) – mediate pain, temperature, noxious stimuli
Sensory axons are present in lamina propria

21. Sensory Innervation of Bladder

22. Capsaicin sensitive sensory fiber
Sensory function – regulating micturition threshold (especially after spinal cord transection), mediating pain, activating cardiovascular responses
Efferent function – activating local motor responses, regulating nerve excitability, local control of vascular blood flow and permeability (neurogenic inflammation ?)

23. Treatment of sensory urgency by intravesical capsaicin
Capsaicin in 10 micro-M can effectively treat hypersensitive disorders
Transient desensitization of capsaicin-sensitive afferents without interfering motor function
Little effect was found in classical Interstitial cystitis
Resiniferatoxin may have similar effects

24. Role of Potassium in pathogenesis of Urgency Frequency Syndrome
Chronic diffusion of urinary potassium into bladder interstitium may induce sensory symptoms, damage tissue, and possibly cause interstitial cystitis
Intravesical potassium test (40ml, 0.4M) is a reliable method for detecting abnormal urothelium permeability

25. Potassium test in Urgency Frequency Syndrome

26. Nerve Growth Factor
Increased nerve growth factor levels in the bladder biopsies from sensory urgency, chronic cystitis, and interstitial cystitis than in controls
Immunostaining showed increased NGF expression in the urothelium, most marked in idiopathic sensory urgency
Anti-NGF treatment may be rational

27. NGF immunostaining in Idiopathic Sensory Urgency

28. Urgency frequency associated with Bladder or perineal pain
Suprapubic pain or perineal pain at bladder fullness
The pain may/not disappear after voiding
A tight sphincter EMG at bladder capacity
Reduced bladder compliance
Urethral obstruction due to stricture or spastic urethral sphincter as etiologies

29. Reduced bladder capacity and Frequency urgency bladder pain

30. Frequency urgency & pain Spastic pelvic floor & sphincter

31. Differential diagnosis of Urgency Frequency Syndrome
History – Bladder injury, foreign body
Urinalysis – UTI
Uroflowmetry – BOO
Cystoscopy – bladder tumor, bladder stone, irradiation cystitis, chronic cystitis
Ultrasound – bladder neck and/or urethral incompetence
Cystometry – low compliance, DI, DESD

32. Pressure flow study for Urgency frequency syndrome
Cystometry can only detect capacity, detrusor instability, compliance, and bladder sensation during filling phase
Pressure flow study can diagnose bladder outlet obstruction, low detrusor contractility, poor relaxation of urethral sphincter, and DESD accurately

33. Urodynamic study in Urgency frequency syndrome- Detrusor overactivity

34. Urodynamic study in Urgency frequency syndrome- Detrusor underactivity

35. Urodynamic study in Urgency frequency syndrome- Bladder outlet obstruction

36. Urodynamic study in Urgency frequency syndrome- Low compliant bladder

37. Urodynamic study in Urgency frequency syndrome- Pseudodyssynergia

38. Urodynamic study in Urgency frequency syndrome- Idiopathic Sensory Urgency

39. LUTS Analysis of Voiding dysfunction
Frequency
(n=233)
Urgency
(n=98)
Dysuria
(n=104)
Incontinence
(n=129)
Bladder pain
(n=34)
Normal bladder & urethra(n=46) 44 17 20 5
Hypersensitive bladder (n=102) 90 38 47 25
Detrusor instability (n=44) 37 22 18 30 6
Low detrusor contractility (n=77) 68 34
Poorly relaxed sphincter (n=76) 40 28 19
Genuine stress incontinence (n=49) 45 2
Bladder outlet obstruction (n=21) 21 13 9

40. Treatment of Frequency urgency syndrome & Normal UDS
Reassurance
Bladder biofeedback
Restrict fluid intake
Avoid diuretics and certain acid foods
Sedatives or mild tranquilizers

41. Foods to be Avoided Acid foods All alcoholic beverages Guava
Apple juice,red and green apples
Lemon juice
Apricots
Nectarines
Cantaloupes
Peaches
Chilis/spicy foods
Plums
Citrus fruits (lemon,lime, orange,etc)
Strawberries
Coffee
Tea
Cranberries
Tomatoes
Grapes
Vinegar

42. Foods high in tyrosine, typtophan, aspartate, and phenylalanine
Avocados
Nutrasweet
(Aspartame)
Chocolate
Saccharine
Bananas
Nuts
Corned beef
Sour cream
Beer
Onions
Cranberries
Soy sauce
Brewer’s yeast
Pickled herring
Fava beans
Vitamins buffered with aspartate
Canned figs
Pineapple
Lima beans
Wines
Champagne
Prunes
Marmite
Yogurt
Cheeses
Raisins
Mayonnaise
Chicken livers
Rye bread

43. Bladder biofeedback for Urgency frequency syndrome
Urodynamic proven sensory urgency
Bladder biofeedback – increased each voiding interval by holding urine for 5 min more
Increase fluid intake gradually
Improved functional capacity (296 v 96ml) and decreased daytime frequency (5.7 v 15.8) and nocturia (0.3 v 2.3) after treatment

44. Intravesical Heparin therapy
Patients with urgency frequency and a positive potassium test
Intravesical Heparin 25000u/10ml saline and holding for 2 hours
2x or 3x per week for 12 weeks
67% patients have improvement in symptoms and increase in bladder capacity

45. The changes of urodynamic parameters before and after heparin treatment
Baseline
3 months
Statistics P value
FSF(ml)
96.5±46.4
146.1±55.4
0.001
US(ml)
225.4±96.2
264.9±84.2
0.009
Cystometric capacity(ml)
262.0±89.8
304.3±84.8
0.002
PdetQmax(cmH2O)
25.7±9.1
28.3±9.3
0.07
Qmax (ml/sec)
12.9±5.7
15.1±7.7
0.063
Residual urine(ml)
29.4±38.4
14.5±25.7
0.096
IPSS (points)
19.5±4.6
9.0±4.0
Nocturia (times/night)
5.7±2.0
2.3±1.1
Pain scale of KCl (points)
3.2±0.5
0.7±0.7

46. Urodynamic finding before and after Heparin Therapy

47. Intravesical Capsaicin Therapy
Patients who are refractory to conventional treatment
Capsaicin M in 30ml N/S instilled to bladder for 30 minutes
Resiniferatoxin 10-8 M in 30ml N/S
A burning sensation or urge at instillation
Relief of pain and urge in the later days

48. Cystometric Results after Capsaicin Instillation
Hypersensitive Bladder
(n=10) IC
Before
After
FSF(ml)
59±21*
27±7.5
75±33*
21±15
FS(ml)
110±28*
55±17
109±32*
34±13
Capacity(ml)
189±30*
82±14
143±31*
59±17
Qmax(ml/sec)
22.8±7.5*
16.5±2.9
19.3±5.4*
12.5±4.7
Corredcted Qmax
1.65±0.5
1.83±0.3
1.62±0.3*
1.63±0.2
*P<0.05

49. A Cocktail Preparation for Idiopathic Urgency Frequency ?
Mixture of Xylocaine, Resiniferatoxin, Heparin, Oxybutynin with certain vehicle
To provide local anesthesia, C-fiber desensitization, repair of defected glycosaminoglycan layer, anticholinergic effect together in one instillation
Clinical trial is undergoing

50. Anticholinergics Treatment
Oxybutynin – the most effective and safe drug currently available
Detrusitol – M3 antagonist, less salivary and GI side effects than ditropan
Flavoxate – mild effect in detrusor
Imipramine – central and anticholinergics

51. DDAVP – Alternative for Urgency Frequency Polyuria
Baseline
Post-treatment
Paired t-test
Nocturnal frequency
(times/night)
5.20±1.16
2.24 ±1.12
P<0.0001
Noctunal urine volume(ml)
955.6±255.9
522.8 ±210.5
Quality of Life
4.47±1.07
1.05 ±0.91
Urine specific gravity
1.012 ±0.007
1.016 ±0.005
P≒0.011
Serum Na (meq/L)
139.5 ±4.34
139.7 ±3.84
P≒ 0.761
Serum K (meq/L)
4.46 ±0.35
4.31 ±0.44
P≒ 0.022

52. Pelvic Floor Exercises for Urgency frequency syndrome
3 sets of 8 to 12 slow velocity maximal pelvic floor muscle contractions
Sustained for 6 to 8 seconds each
Performed 3 to 4 times a week
Continued for at least 15 to 20 weeks

53. Results of Pelvic Floor Exercises
Increased maximal cystometric capacity
Fewer detrusor contractions
Less incontinence episodes
Expected cure/improvement rates 65-75%
About 50% of patients avoid surgery

54. Changes of Bladder sensation after Pelvic Floor Exercises
Pre-treatment
Post-treatment
Statistics (p value)
Qmax (mL/s)
Total
22.6 ± 13.0
20.9 ± 10.2
0.390
Successful
26.0 ± 10.77
23.4 ± 10.7
0.236
Failure
18.3 ± 14.9
17.8 ± 9.2
0.881
Voided volume
340.5 ± 123.4
386.1 ± 152.9
0.240
395.4 ± 69.8
414.1 ± 176.3
0.780
273.3 ± 144.5
351.9 ± 119.4
0.021
FSF (mL)
101.0 ± 26.8
128.2 ± 41.6
0.025
96.1 ± 21.1
136.4 ± 45.8
0.027
107.0 ± 32.7
118.1 ± 35.7
0.484
FS (mL)
189.0 ± 47.5
229.5 ± 46.9
0.006
190.4 ± 51.4
245.0 ± 47.4
0.015
187.3 ± 45.2
210.4 ± 40.9
0.218

55. Increased Voluntary Contractility after Pelvic Floor Exercises

56. Cystometrographic Biofeedback
Under direct visualization of detrusor activity or involuntary detrusor contractions, patients are instructed to hold urine as strongly as possible
Pressure flow study with patient sitting on commode with a uroflowmeter

57. Detrusor instability and Holding urine during involuntary DI

58. Neuromodulation for Urgency frequency syndrome
Surface neuromodulation at suprapubic area
Sacral nerve stimulation from sacral foramina
Electromagnetic stimulation
Interferential current electrostimulation of pelvic floor muscles
Other transcutaneous neuromodulation

59. The Anxious Bladder