1. Pathophysiology of OAB
Jun Jang
Deajeon St. Mary’s Hospital

2. Pathophysiology of OAB
Contents
Definition of OAB 3 1
Symptoms of OAB 2
Pathophysiology of OAB 3
Conclusions 4

3. Definition of Overactive Bladder
Definition of Overactive Bladder
a symptom syndrome
Urinary urgency, with or without urge incontinence, usually accompanied by frequency and nocturia
No signs of other pathology or infection
Abrams P et al. Neurourol Urodyn. 2002;21:

4. Symptoms of Overactive Bladder
Symptoms of Overactive Bladder
Urgency; the complaint of a sudden compelling desire to pass urine, which is difficult to defer
Urge urinary incontinence; the complaint of involuntary loss of urine accompanied by or immediately preceding by urgency
Frequency, Nocturia
Abrams P et al. Neurourol Urodyn. 2002;21:

5. Pathophysiology of OAB
Pathophysiology of OAB
Neurogenic
Detrusor Overactivity
Myogenic

6. Pathophysiology of OAB
Pathophysiology of OAB
a sudden increase in intravesical pressure at low volumes during the filling phase
increased spontaneous myogenic activity
fused tetanic contractions
altered responsiveness to stimuli
characteristic changes in smooth muscle ultrastructure

7. Morphologic changes of the detrusor
Morphologic changes of the detrusor
patchy denervation
increased coupling
enlarged sensory neurons
increased spinal micturition reflex
Regardless of the etiology, unstable detrusor develops common changes
in the macroscopic structure of the bladder.

8. Morphologic changes of the detrusor
Morphologic changes of the detrusor
Patchy denervation of the detrusor muscle bundles in bladder biopsies of OAB patients
→ a notable increase in connective tissue between normal muscle bundles
; Increased infiltration of connective tissue
→ complete denervation
hypertrophy of the smooth muscle
incomplete emptying of the bladder
during micturition
Unstable human bladders frequently show patchy denervation of the muscle bundles. Some muscle fascicles may be completely denervated, while neighboring bundles appear normal. Other regions may show intermediate innervation. The areas of reduced innervation become infiltrated with connective tissue. After complete denervation, hypertrophy of the smooth muscle cells occurs.

9. Morphologic changes of the detrusor
Morphologic changes of the detrusor
Lack of electrical coupling in normal bladder
- Detrusor; made up of smooth muscle bundles
- allows the bladder to ignore irrelevant electrical impulses that would otherwise cause an unwarranted response.
Unstable bladder; increased coupling of smooth muscle
→ increased excitability in the event of inadvertent low-grade efferent stimuli triggering the sense of urgency and culminating in an involuntary contraction
age related or a result of nerve damage from disease, injury, or obstruction.
At an ultrastructural level, a common feature in unstable detrusor is the presence of protrusion junctions and ultra-close abutments between the myocytes. This picture is rare in the normal detrusor and may represent the morphologic correlate to increased electrical coupling in unstable bladders

11. Neurological changes Neuroplasticity
Neurological changes
Neuroplasticity
the ability of the nervous system to change transmitters, reflexes, or synaptic transmission in the event of disease or injury
afferent neurons in the dorsal root ganglia enlarge
→ a shortened delay in the central transmission of the micturition reflex
The micturition pathway is reorganized from a spinobulbospinal loop to a predominantly spinal network.
Activation of secondary excitatory parasympathetic afferents (myelinated Aδ- and unmyelinated C-fibers), which are usually silent, can then trigger micturition.

12. Afferent Plasticity in the Inflamed or Obstructed Bladder
Afferent Plasticity in the Inflamed or Obstructed Bladder
3. Enhanced synaptic transmission: increased expression of GAP-43 and axonal sprouting
Afferent neuron
Dorsal horn interneuron
2. Recruitment of lower-threshold, spontaneously firing afferents
4. Storage Symptoms (?)
Preganglionic neuron
Sacral spinal cord
1. Irritated or obstructed bladder
Parasympathetic postganglionic neuron
GAP-43 = growth-associated protein 43
Adapted from Steers WD. Rev Urol. 2002;4:S7-S18.

13.
Neurological changes
Ischemia → nerve injury → smooth muscle damage & impaired contractility
Peripheral vascular disease, benign prostatic hyperplasia, urethral stricture, detrusor–sphincter dyssynergia, or diabetic neuropathy
→ may cause severe obstruction, reduced blood flow, and neuronal death
The coexistence of neurologic factors and ischemia gives rise to detrusor hyperactivity with impaired contractility or unstable contractions in the absence of sensation of urgency.

14.
Neurological changes
A possible molecular trigger for changes in bladder afferents or synaptic transmission in the CNS
Nerve growth factor
- a naturally occurring molecule
- stimulates growth and differentiation of the sympathetic and certain sensory nerves
- responsible for neuronal regrowth after injury
Patients with OAB, benign prostatic hyperplasia, or interstitial cystitis may have elevated levels of nerve growth factor in their bladders.

15. OAB, Neurogenic DO may result from DO may reflect
OAB, Neurogenic
DO may result from
Decreased central inhibitory control
Increased afferent activity
Increased detrusor sensitivity to motor input
DO may reflect
Cerebrovascular disease
Neurologic disease

16. OAB, Myogenic DO may result from DO is reflected by
OAB, Myogenic
DO may result from
Alterations in structural and functional properties of the detrusor muscle
Partial denervation of the detrusor muscle
DO is reflected by
Abnormal spontaneous mechanical activity
Supersensitivity to acetylcholine (ACh)
Increased sensitivity to direct electrical stimulation
Depressed responses to intrinsic nerve stimulation

17. Pathophysiology of mixed UI
Pathophysiology of mixed UI
Unclear and multifactorial
Entrance of urine into the proximal urethra during descent and opening of the bladder neck
 evoke urethro-detrusor facilitative reflex
 stimulate afferent n. of the bladder
 detrusor contraction
Bump RC. Obstet Gynceol Report 1990(2);

18. Potential Etiology of OAB in Men With BPO
Potential Etiology of OAB in Men With BPO
Supersensitivity to Ach
Reduced response to intramural nerve stimulation
Partial denervation
Ischemia
Increased electrical coupling between cells
Hypertrophy/hyperplasia
Instability of membrane potential
Altered intracellular Ca2+-regulation
Outflow Obstruction
Detrusor muscle
Overactive bladder
Reorganization of spinal micturition reflex (C-fiber-mediated)
Altered Na+ channel expression/function
Expression of nerve growth factor
Hypertrophy of afferent and efferent neurons
Steers WD. Rev Urol. 2002;4:S7-S18

19. Detrusor hyperactivity and impaired contractility in elderly patients
Detrusor hyperactivity and impaired contractility in elderly patients
symptoms and cystometric evidence of bladder overactivity are found together with incomplete emptying that is not caused by obstruction.
Histologic changes in the bladders of aging humans have provided evidence of changes in cell-to-cell connections manifested by increased protrusion junctions.
In patients with impaired contractility, there was also degeneration of muscle cells and nerve axons
Elbadawi A, et al. J Urol 1997;157:1814–1822

20.
OAB in the elderly
caused by age-related diseases that indirectly alter normal urinary tract function
Metabolic, degenerative, or neurogenic diseases
Stroke, Alzheimer disease, multi-infarct or other dementias, Parkinson disease, or multiple sclerosis
→ may impair higher cortical inhibition of the bladder
→ neurogenic detrusor overactivity
DM → poor blood glucose control → osmotic diuresis and polyuria
Sleep disorders → nocturia
Disorders of the PFM(POP, fecal incontinence) → lessen their capacity to resist sudden increases in intravesical bladder pressure during the filling phase → bladder control problems, especially SUI

21. Hypersensitivity-induced overactivity
Hypersensitivity-induced overactivity
Unmyelinated, capsaicin-sensitive C-afferents
- mediate pain
- contribute to other sensations of bladder fullness and urgency
normally inactive; “silent C-fibers”
During neuropathic conditions and possibly inflammatory conditions, there is recruitment of C fibers that form a new functional afferent pathway that can cause urge incontinence and possibly bladder pain.

22. Idiopathic bladder overactivity
Idiopathic bladder overactivity
Denervation in biopsy specimens from humans with clinical evidence of OAB
→ muscle abnormalities may be a frequent cause
some sort of change in smooth muscle properties may be a necessary prerequisite for bladder overactivity.
Mills IW et al. J Urol 2000;163: 646–651
Brading AF. Urology 1997;50(S6A): 57–67; discussion 68–73
Brading AF et al. Br J Urol 1994;73: 3–8

23. Other causes Depression or anxiety
Other causes
Depression or anxiety
OAB more often than the general population.
associated with disturbances in brain circuits using specific neurotransmitters, in particular serotonin (5-hydroxytryptamine, or 5-HT).
Actions of 5-HT; very complex
- facilitating effect on voiding via modulation of bladder afferents, volume thresholds, and bladder contractions

24.
Conclusions
The ICS definition of overactive bladder emphasizes the symptomatic nature of the disease
The symptoms of OAB is originated from the change in both afferent neuron and detrusor.
Modulation of these components appears to be a promising area for clinical intervention in the management of OAB.

25. Thank You !