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Interstitial Cystitis Painful Bladder Syndrome

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

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  1. Interstitial CystitisPainful Bladder Syndrome Hann-Chorng Kuo Department of Urology Buddhist Tzu Chi General Hospital Hualien

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. Glomerulation and petechia

  13. Increased vasculature in a man with IC

  14. 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

  15. 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

  16. 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)

  17. 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

  18. Symptomatology of 30 IC

  19. Uroflowmetry in IC patients

  20. Various Types of Abnormal Uroflowmetry in IC (1)

  21. Various Types of Abnormal Uroflowmetry in IC (2)

  22. Various Types of Abnormal Uroflowmetry in IC (3)

  23. 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

  24. Urodynamic results in IC

  25. 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

  26. Normal and abnormal cystometry in IC

  27. Abnormal cystometry in IC (1)

  28. Abnormal cystometry in IC (2)

  29. Abnormal cystometry in IC (3)

  30. Pathological findings in IC

  31. Microscopic finding in early IC

  32. Microscopic findings in Chronic IC

  33. 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

  34. Detrusor Mastocytosis in IC

  35. 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

  36. Bladder mucosa and vasculature

  37. 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

  38. Increased bladder mucosal permeability • Acute bacterial cystitis • Chronic cystitis • Foreign body, calculi, tumor • Overdistension • Acidic fluid or toxin substance • Surgical trauma or instrumentation

  39. 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

  40. 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

  41. 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

  42. 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

  43. 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)

  44. 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

  45. 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

  46. 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

  47. Urodynamic finding before and after Heparin Therapy

  48. The changes of urodynamic parameters before and after heparin treatment

  49. 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

  50. 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

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