Infarct cerebral, parkinsons disease

Cerebrovascular disease (e.g. strokes,

etc)

Supra-pontine lesion and damage the

cerebral cortex

Impaired micturition reflex

Impaired glutamatergic
pathway in CNS

Impaired central
dopaminergic pathway

Mediated by NMDA
glutamatergic excitatory
mechanism

Mediated by D2
dopaminergic excitatory
mechanism

Imbalance function of excitatory and

inhibitory regulation of micturition

Bladder over-activity

Vertebrae trauma or etc

Spinal cord lesion

Damage the lumbo-sacral level

Impaired voluntary and supraspinal

reflex pathways

Impaired
parasympathetic
pathways (s2-s4)

Impaired emptying
bladder mechanism

Impaired sympathetic
pathways (T11-L2)

Impaired storage bladder

mechanism

Bladder over-activity and

overflow

Impaired sacral somatic

pathways (Onufs
nucleus)

Impaired contraction of
urethral sphincter

Benign prostatic enlargement

Bladder outlet obstruction

intra-vesical pressure during

voiding

tissue pressure of hypertrophied

bladder wall during filling

HYPERTROPHY

Nerve structural

Impaired density of the nerve

structures

Alter total density

Nerves gene expression

Absence of cholinergic nerve

terminals

Relative functional
role of MR subtypes

Change of muscarinic
receptor (MR) expression

Alteration in 1 and/or
adrenergic receptor

1-adrenergic
receptor

-adrenergic receptor

1A-ARs expression
& little expression of
1D receptor

3 receptor
expression

 in mRNA expression
of M2 and M3
receptors

contractionmediated 1adrenergic receptor

relaxation mediated
-adrenergic receptor

Denervation

Super-sensitivity other
agonists such as high
potassium

Super-sensitivity to
acetylcholine

Bladder over-activity

Reduc3e response to
intramural nerve
stimulation

Bladder outlet obstruction

force required to expel urine

augmented urethra resistance

HYPERTROPHY

Compensation phase

decompensating phase

Increase muscle contractility

Bladder dysfunction

transverse area of smooth

muscle

Impaired of myosin heavy chains

Muscle bundle become

longer and larger

Impaired interaction of myosin II

ATP-ase and actin

SM2 and SM1 ratio decrease or

increase

Deteriorate the contractile function

Bladder over-activity

Detrusor smooth muscle

Cholinergic agonists bind to MRs

[Ca2+] intracellular increase

Induce calmodulin (calciummodulated protein)-mediated

activation MLC-kinase

NORMAL

Phosphorylates MLC

Induced smooth muscle contraction

[Ca2+] intracellular return to its

baseline level

Maintaining contraction by calcium

sensitization mechanism independent
of [Ca2+] intracellular

Regulate by

Rho-kinase (ROK)

Protein kinase C (PKC) activation

Bladder obstruction outflow

Alters the expression of ROK isoforms

ROK or ROK

Force generated in obstructive

bladder

ROK pathway responsible for force

maintenance response in
decompensate bladder

Deteriorate the detrusor smooth

muscle

Bladder over-activity

Older age in women, menopause

phase, ovanektomy

Estrogen level
stretch-induced Ach release

Ach release from cholinergic nerves

Rho-kinase
detrusor contractility

Detrusor muscle tone

Impaired contractility

bladder compliance

Bladder overactivity

Vaginal delivery

Compression by the
presenting part of the
fetus during laboring

Injury to connective
tissue supports by the
mechanical process of
vaginal delivery (e.g
forceps delivery)

Trauma during
parturition

Damage to the pelvic

nerves and/or muscles

Vascular damage to the

pelvic structure

The medial pubo-coccygeus

muscle undergo the largest
stretch of any musculus levator
ani

Risk for stretch-related injury

Bladder over-activity

Damage pelvic floor

Bladder-supporting bone
impaired

Damage pelvic floor

Bladder-supporting bone
impaired

Direct injury to the

urinary tract