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Pathophysiology of OAB. Jun Jang Deajeon St. Mary’s Hospital. 3. 3. Definition of OAB. 1. 3. Symptoms of OAB. 2. Pathophysiology of OAB. Conclusions. 4. Contents. Definition of Overactive Bladder. a symptom syndrome - PowerPoint PPT Presentation
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Contents
Symptoms of OAB2
Conclusions4
Definition of OAB31
Pathophysiology of OAB33
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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;21:167-178.
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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;21:167-178.
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Pathophysiology of OAB
Neurogenic
Myogenic
Detrusor Detrusor OveractivityOveractivity
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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
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Morphologic changes of the detrusor
patchy denervation increased coupling enlarged sensory neurons increased spinal micturition reflex
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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
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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.
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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.
www.themegallery.comAfferent Plasticity in the Inflamed or
Obstructed Bladder
Parasympathetic postganglionic
neuron
Sacral spinal cord
1. Irritated or obstructedbladder
Preganglionicneuron
Dorsal horn interneuron
3. Enhanced synaptic transmission: increased expression of GAP-43 and axonal sprouting
Adapted from Steers WD. Rev Urol. 2002;4:S7-S18.
2. Recruitment of lower-threshold, spontaneously firing afferents
GAP-43 = growth-associated protein 43
4. Storage Symptoms (?)
Afferent neuron
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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.
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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.
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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
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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
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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);295-302
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Potential Etiology of OAB in Men With BPO
Reorganization of spinal micturition reflex(C-fiber-mediated)Altered Na+ channel
expression/function
Outflow Obstruction
Detrusor muscle
Increased electrical coupling between cells
Hypertrophy/hyperplasiaInstability of membrane potential Altered intracellular Ca2+-regulation
Overactive bladder
Expression of nerve
growth factor
Partial denervation
Hypertrophy of afferent and efferent neurons
Supersensitivity to AchReduced response to intramural nerve stimulation
Steers WD. Rev Urol. 2002;4:S7-S18
Ischemia
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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
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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
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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.
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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: 646–651Brading AF. Urology 1997;50(S6A): 57–67; discussion 68–
73Brading AF et al. Br J Urol 1994;73: 3–8
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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
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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.