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Interstitial Cystitis Painful Bladder Syndrome. Hann-Chorng Kuo Department of Urology Buddhist Tzu Chi General Hospital Hualien. Interstitial cystitis. A syndrome of mystery in urology A diagnosis of exclusion

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interstitial cystitis painful bladder syndrome

Interstitial CystitisPainful Bladder Syndrome

Hann-Chorng Kuo

Department of Urology

Buddhist Tzu Chi General Hospital Hualien

interstitial cystitis
Interstitial cystitis
  • A syndrome of mystery in urology
  • A diagnosis of exclusion
  • Triad diagnostic characteristics –Suprapubic pain at full bladder and relieved after voiding, with severe frequency and nocturia

Sterile urine

Characteristic cystoscopic findings

diseases associated with ic
Diseases associated with IC
  • Allergies, autoimmune diseases, rheumatic disease,irritable bowel syndrome
  • A common pathophysiology mediated by immune, endocrine & neurologic dysfunction
  • Systemic lupus erythematosus
  • The role of mast cell (increase histamine release from bladder biopsies) in IC
epidemiology of ic
Epidemiology of IC
  • In a survey of USA Nurse’s health Study, self-reported IC was 0.4% (357 in 91155 NHSI) and 1.4% (1354 in 993428 NHSII)
  • NIDDK criteria is too restrictive, about 60% excluded patients may have IC
  • The prevalence of IC was estimated to be 52 per 105 (NHSI) and 67 per 105
possible pathogenesis of ic
Possible pathogenesis of IC
  • Post-infection autoimmune process
  • Mast cell activation – inflammation, toxin, stress
  • Urothelial dysfunction – increased permeability of urothelium
  • Neurogenic inflammation – K diffusion- mast cell activation – upregulation of sensory fiber – release of neuropeptide (substance P) – neurogenic inflammation – pain in IC
characteristic cystoscopic findings after hydrodilatation
Characteristic cystoscopic findings after hydrodilatation
  • Classical IC – contracted bladder, Hunner ulcer
  • Early IC – glomerulation, petechial hemorrhage, mucosal fissure
  • Recent investigations revealed classical IC may be misleading, chronic IC may be more accurate to describe pathology
interstitial cystitis7
Interstitial cystitis
  • 1915 Hunner – an elusive ulcer after secondary bladder hydrodilation
  • 1949 Hand – Female tomale ratio 11:1
  • 1975 Oravisto – incidence about 18/105
  • 1978 Messing – Glomerulation after hydrodilatation
  • 1982 Larsen – mast cell quantitative assessment in IC
  • 1983 Parsons – a defect in bladder GAG layer
  • 1987 Holm-Bentzen – painful bladder syndrome
  • IC remains a syndrome of unknown etiology, difficult to diagnosis and treatment
ic patient accrual form niddk 1987 automatic exclusion
IC patient accrual form –NIDDK 1987 automatic exclusion
  • Less than 18 years old
  • Benign or malignant bladder tumor
  • Irradiation cystitis
  • Tuberculous cystitis
  • Bacterial cystitis
  • Vaginitis
  • Cyclophosphamide cystitis
  • Symptomatic urethral diverticulum
  • Uterine, cervical, vaginal, or urethral cancer
ic patient accrual form automatic exclusion
IC patient accrual form-- automatic exclusion
  • Active herpes
  • Bladder or lower ureteral calculi
  • Waking frequency < 5/12 hours
  • Nocturia <2/night
  • Symptoms relieved by antibiotics, urinary antiseptics, analgesics
  • Involuntary detrusor contractions
  • Capacity > 400ml, no sensory urgency
ic patient accrual form automatic inclusions
IC patient accrual form-- automatic inclusions
  • Hunner’s ulcer
  • Positive factors –
  • Pain on bladder filling relieved by emptying
  • Pain (suprapubic, pelvic, urethral, vaginal, perineal)
  • Glomerulation on endoscopy
  • Decreased compliance on cystometry
  • Bladder distention by 80 cm water x 1 min, two positive factors are necessary
cystoscopic hydrodilatation
Cystoscopic Hydrodilatation
  • Intravenous general anesthesia or spinal anesthesia
  • Inserting cystoscopy lightly, do not evacuate bladder completely
  • Inspection the whole bladder for vasculature and lesions
  • The fluid level is set at 80 cm water above symphysis pubis
  • Fully distended the bladder
  • Evacuation of the bladder slowly and observe any glomerulation, petechial, splotch hemorrhage or mucosal laceration
  • Refilled the bladder and check ulceration
  • Take bladder biopsy if necessary
interstitial cystitis in men
Interstitial cystitis in Men
  • Less than 10% of IC are men
  • 35/60 (58%) men with non-bacterial prostatitis or prostatodynia had petechiae following cystoscopic dilation
  • In 29 men with IC, misdiagnosis wasmade as prostatitis (48%), BPH (38%)
  • Carcinoma in situ should be ruled out
management after cystoscopic hydrodilatation for ic
Management after cystoscopic Hydrodilatation for IC
  • Indwelling a Foley catheter especially after bladder biopsy
  • Adequate hydration
  • Hemorrhage is usually not a problem
  • Analgesics for severe irritative symptoms
  • Remove the catheter after fully awakened
basic urodynamic abnormalities
Basic urodynamic abnormalities
  • Sensory urgency
  • Intolerance to increments of bladder volume
  • Decrease in bladder compliance <30ml/cm water (16/30 v 3/17 PBS, p<0.025)
  • Smaller maximal capacity under anesthesia (548 v 612, p<0.05)
urodynamic findings in ic
Urodynamic findings in IC
  • 50 patients with painful bladder underwent urdynamic study and cystoscopic hydrodilation
  • 30 (28 F & 2 M) had characteristic IC, 20 non-IC
  • Symptomatology was indifferent between IC & non-IC
uroflowmetry in ic
Uroflowmetry in IC
  • Most IC patients present with abnormal flow pattern
  • With or without a low maximal flow rate (22/28), but this feature also can be found in non-IC (11/16)
  • Can rule out other hypersensitive bladder and bladder outlet obstruction
urodynamic parameters in ic
Urodynamic parameters in IC
  • Bladder hypersensitivity FSF <100ml
  • A trend toward smaller capacity in chronic cases
  • Most have normal compliance in early IC and decreased compliance in classic IC
  • Most have a normal flow rate
  • Urethral pressure profile has no clinical value
  • As prognostic indicators and surgical results
microscopic findings in ic
Microscopic findings in IC
  • Classical IC – mucosal ulceration with granulation tissue; marked mononuclear cell infiltration; increased mast cell in lamina propria and detrusor; presence of intraurothelial mast cell; perineural inflammatory cell; significant fibrosis
  • Early IC – mucosal rupture; suburothelial hemorrhage; scanty inflammation and mild submucosal edema
physiology of micturition
Physiology of Micturition
  • Bladder sensation: first sensation 150ml, full sensation 250-350ml, urge sensation 400-500ml
  • Sensory afferents – reflex center S2-4 – micturition center (pons) – cerebral cortex
  • Voiding pressure in women 20-40 cm water, men 30-50 cm water
vesical blood urine barrier
Vesical Blood Urine barrier
  • Urothelium appears to be a functional extension of renal collecting duct
  • Absence of barrier allows recirculation of renal waste and deteriorate function
  • 13:1 mucosal to muscular blood flow in bladder wall ratio imply a barrier function for blood-urine compound exchange and equilibrium
increased bladder mucosal permeability
Increased bladder mucosal permeability
  • Acute bacterial cystitis
  • Chronic cystitis
  • Foreign body, calculi, tumor
  • Overdistension
  • Acidic fluid or toxin substance
  • Surgical trauma or instrumentation
increased permeability of bladder epithelium
Increased permeability of Bladder epithelium
  • Bladder capacity was decreased by K, hyperosmolar, and PH5; while increased by hypoosmolarity electrolyte free media, furosemide, and PH8
  • Normal subjects absorbed 4.3%, IC 25% of concentrated urea from bladder
  • Frequent voiding reduced urinary contact time, protecting from urine recirculation
pathophysiology of leaky epithelium and cystometry
Pathophysiology of Leaky epithelium and cystometry
  • Impairment of blood urine barrier led to a decrease in compliance and capacity
  • Isotonic KCl and hyperosmolar NaCl induced an immediate onset of voiding contraction in rat bladders
  • CMG in normal bladder revealed no such effects of KCl & hyperosmolar NaCl
  • Urge sensation and pressure are elicited in diseased human bladder after intravesical K
potassium and bladder control
Potassium and Bladder control
  • Bladder sensory afferent pathway relative to submucosal K and intramuscular proprioceptor to to intravesical pressure and tension
  • Intravesical K or hyperosmolarity affects exteroception resulting in reflective storage pressure elevation and urge proprioception
  • Local or perimuscular K enhancement facilitates onset of voiding contraction
glycosaminoglycan frequency urgency syndrome
Glycosaminoglycan & Frequency urgency syndrome
  • A subset of frequency urgency syndrome has a leaky epithelium and cations (K) can diffuse subepithelially and provoke urgency frequency
  • Intravesical KCl (0.4M) provoked symptoms in 4.5% normal, 70%IC, 18% heparin treated IC, 100% irradiation cystitis
  • Intravesical sulfated polysaccharide can restore injured urothelium to normal
pathophysiology of leaky epithelium
Pathophysiology of Leaky Epithelium
  • Hyperosmolar NaCl concentration decreased more rapidly in over-distension, retention, bacterial and chronic cystitis
  • Serious water inflow and recirculation of renal waste occurred in urine retention
  • In experimental cystitis, slow blood flow rate resulted in maximal hyperosmolar suburothelial urea accumulation (maximal exchange)
treatment of interstitial cystitis
Treatment of Interstitial Cystitis
  • Cystoscopic hydrodilatation
  • Intravesical heparin therapy
  • Intravesical DMSO instillation
  • Intravesical capsaicin or resiniferatoxin
  • Sodium pentosan polysulfate (PPS, Elmiron)
  • Amitriptynin
  • Supratrigonal cystectomy augmentation
medical treatment of ic
Medical treatment of IC
  • Cyclosporine
  • Methotrexate
  • Tice strain BCG– 60% response rate vs 27% in placebo
  • Elmiron (PPS 100mg tid) – 6.2% to 18.7% response rate
  • Electromotive administration of intravesical lidocaine & dexamethasone – 62% effective
inravesical heparin therapy
Inravesical 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
intravesical capsaicin therapy
Intravesical Capsaicin Therapy
  • Capsaicin in 10 uM concentration instilled intravesically 1/week to 10 women with hypersensitive bladder(HSB) and 10 with interstitial cystitis, a total 6 weeks
  • 8 HSB responded for 3-5 days, 2 IC responded for 2-3 days
  • No reported side effects
cystoscopic hydrodilatation50
Cystoscopic hydrodilatation
  • Under general or spinal anesthesia, at pressure of 80cm water, the bladder was distended for 30min
  • Effective in relieving symptoms after hydrodilatation
  • The increased bladder capacity was limited
  • Regular hydrodilatation is needed
cystectomy augmentation
Cystectomy & augmentation
  • Supratrigonalor subtrigonal cystectomy plus enterocystoplasty are effective
  • Major operation with complication
  • Residual LUTS including pain persist in 30% of patients
  • Only suitable in severe classical IC
bladder autoaugmentaton
Bladder autoaugmentaton
  • A minor operation to relieve intravesical pressure
  • Myomectomy or detrusectomy and open bladder wall
  • Increased bladder capacity and pain at full bladder can be relieved
  • Covering of omentum or de-epithelial bowel musculature will be helpful
conclusions
Conclusions
  • Interstitial cystitis is more prevalent than previously realized
  • A multiplicity of dynamic pathophysiological processes in bladder
  • Vicious circle of increased urothelial permeability, inflammation, and nerve sensitization leads to chronicity of IC
ad