Pathophysiology of OAB

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Pathophysiology of OAB

Jun Jang

Deajeon St. Mary’s Hospital


Contents

Symptoms of OAB2

Conclusions4

Definition of OAB31

Pathophysiology of OAB33


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.


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.


Pathophysiology of OAB

Neurogenic

Myogenic

Detrusor Detrusor OveractivityOveractivity


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


Morphologic changes of the detrusor

patchy denervation increased coupling enlarged sensory neurons increased spinal micturition reflex


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


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.


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


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.


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.


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


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


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


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


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


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


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.


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


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


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.

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Pathophysiology of OAB

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