Pathophysiology of Female LUTS

Lower urinary tract symptoms are resulted from lower urinary tract dysfunction. The
pathophysiology of failure of the lower urinary tract in the adult to fill with or store urine
adequately or to empty adequately must logically be secondary to reasons related to the
bladder, the outlet, or a combination (Wein et al., 1988). Table 1 presents the functional
classification and possible mechanisms of lower urinary tract dysfunction.

1 Storage Dysfunction
Bladder overactivity (involuntary contraction or decreased compliance) and decreased
outlet resistance may cause absolute or relative failure of the bladder to store urine
adequately.

1.1 Bladder Overactivity

Overactivity of the bladder during storage phase can be presented as phasic
involuntary contractions, as decreased compliance, or as a combination.
Involuntary contractions are most commonly seen in association with neurologic
disease or injury, bladder outlet obstruction, stress urinary incontinence (perhaps
because of sudden entry of urine into the proximal urethra, eliciting a reflex
contraction), aging (probably related to neural degeneration), or may be truly
idiopathic.

(Wein A. and Moy M., 2008)

Overactive bladder syndrome (OAB), characterized by daily frequency,

nocturia and urgency with or without incontinence, is a widespread medical
condition with significant impact on quality of life. Alterations in nerve and smooth
muscle

excitability

and

changes

in

bladder

urothelium

composed

of

neurotransmitters, sensory receptors, and specific ion channels are linked with
overactive bladder.(Meng et al., 2012) Metabolic effects, inflammatory reaction,
and bladder outlet obstruction also contribute to the pathophysiology of OAB.

Decreased compliance during storage phase may be secondary to neurologic

injury or disease, usually at a sacral or infrasacral level, but may result from any
process that impairs or destroys the viscoelastic or elastic properties of the bladder
wall.(Wein et al., 2008)
Bladder-related storage failure may also occur in the absence of overactivity
because of increased afferent input from inflammation, irritation, other causes of
hypersensitivity, and pain. The causes may be chemical, psychologic, or idiopathic.
One classic example is painful bladder syndrome, a term that is replacing interstitial
cystitis.(Wein, 2011b)

1.2 Bladder Outlet Underactivity

Urethral support is important in the female, the urethra normally being supported
by the action of the levator ani muscles through their connection to the endopelvic
fascia of the anterior vaginal wall. Damage to the connection between this fascia
and this muscle, damage to the nerve supply, or direct muscle damage can
therefore influence continence. Bladder neck function is likewise important, and
loss of normal bladder neck closure can result in incontinence despite normal
urethral support. (Wein et al., 2008)
1.2.1 Bladder neck hypermobility
Genuine stress incontinence in the female is associated with hypermobility of the
bladder neck, with poor pelvic support, and with an outlet that is competent at
rest but loses its competence only during increases in intra-abdominal pressure.
In approximately 50% of continent women, urine enters the urethra during
increases in abdominal pressure. The continence point in these women is at the
middle of the urethra, where urine is stopped before it can escape from the
of DeLancey (1994) proposes
urethral meatus. The hammock hypothesis
that for stress incontinence to occur within hypermobility, there must be a lack of

stability of the suburethral supportive layer. This theory proposes that the effect
of abdominal pressure increases on the normal bladder outlet, if the suburethral
supportive layer is firm, is to compress the urethra rapidly and effectively. If the
supportive suburethral layer is loose or movable, or both, compression is not as
effective.
1.2.2 Intrinsic sphincter deficiency
Intrinsic sphincter dysfunction denotes an intrinsic malfunction of the urethral
sphincter mechanism itself. It is characterized by a bladder neck that is open at
rest and a low abdominal leak point pressure and urethral closure pressure. It is
usually the result of prior surgery, trauma with scarring, or a neurologic
lesion.(Wein et al., 2008)

Emptying/Voiding Dysfunction
Absolute or relative failure to empty the bladder results from decreased bladder
contractility (a decrease in magnitude or duration), increased outlet resistance, or a
combination.
2.1 Detrusor Underactivity
Absolute or relative failure of bladder contractility may result from temporary or
permanent failure or impairment in one of the neuromuscular mechanisms necessary
for initiating and maintaining a normal detrusor contraction. Inhibition of the voiding
reflex in a neurologically normal individual may also occur; it may be by a reflex
mechanism secondary to increased afferent input, especially from the pelvic and
perineal areas, or may be psychogenic. Non-neurogenic causes also include
impairment of bladder smooth muscle function, which may result from overdistention,
various centrally or peripherally acting drugs, severe infection, or fibrosis.(Wein et al.,
2008)
2.2 Bladder Outlet Overactivity or Obstruction

Pathologically increased outlet resistance is much more common in men than in

women. Although it is most often secondary to anatomic obstruction, it may be
secondary to a failure of relaxation or active contraction of the striated or smooth
sphincter during bladder contraction. Striated sphincter dyssynergia is aother common
cause of functional or nonanatomic (as opposed to fixed anatomic) obstruction in
patients with neurologic disease or injury. A common cause of outlet obstruction in the
female is compression or fibrosis following surgery for sphincteric incontinence.(Wein,
2011b)
2.3 Idiopathic Urinary Retention: Fowler's Syndrome
In 1986, Fowler and Kirby identified a group of 19 young women with long-standing
urinary retention who had distinctive electromyographic activity and impaired urethral
relaxation.(Fowler et al., 1986) The impairment identified by Fowler and Kirby was
referred to as decelerating bursts and complex repetitive discharges (CRDs). CRDs are
caused by direct spread of electrical activity form one muscle fiber to another,
producing a low jitter sound on the audio output of the electromyographic machine.
The bursts of depolarizing activity in the semicircular urethral sphincter muscle impair
normal relaxation of the muscle.(Fowler et al., 1985) This impedes normal bladder
emptying, causing an insidious increase in residual volumes and bladder
distention.(Padmanabhan et al., 2008)

3 Neurogenic Disorder and LUTS

Many neurologic conditions can be associated with lower urinary tract dysfunction;
however, the more commonly known conditions of which urologists should be
particularly aware include: traumatic brain injury, spinal cord injury (SCI),
stroke/cerebrovascular

accident,

multiple

sclerosis,

Parkinsons

disease,

myelomeningocele (MMC), brain or spinal cord tumor, transverse myelitis, back or

spine disease (including herniated disk, cauda equina syndrome), diabetes, peripheral

nerve injury and other lower motor neuron diseases. One well-accepted classification
system based on the location of the neurologic lesion in neurogenic bladder may be
used to guide pharmacologic therapies and other interventions.(Dorsher et al., 2012;
Ginsberg, 2013)
Lesions above the brain stem: The loss of the normal inhibition of a reflexic bladder
contraction results in detrusor overactivity. Common symptoms include urinary
frequency, urgency, and urge urinary incontinence. Bladder sensation can be
normal to decreased. The urinary sphincters should be synergistic with the bladder
(ie, relax when the bladder contracts); thus, high bladder pressures should not
develop. Detrusor areflexia can occur in some patients, either initially and
temporarily or manifesting as permanent dysfunction.
Complete suprasacral spinal cord lesions: These patients exhibit detrusor
overactivity that may lead to urinary incontinence. In addition, detrusor-external
sphincter dyssynergia can be found leading to obstructive voiding and incomplete
bladder emptying. Sensation to bladder filling can be normal to decreased. In
addition, if the lesion is located above T6, the patient may experience autonomic
hyperreflexia.
Trauma or disease to the sacral spinal cord: These patients exhibit detrusor
arreflexia and do not usually have involuntary bladder contractions. Depending on
the type and extent of neurologic injury, decreased bladder compliance may occur
during filling. An open smooth sphincter area may result but the striated sphincter
may exhibit varied types of dysfunction, although this area usually maintains a
resting sphincter tone and cannot be controlled voluntarily. Sensation to bladder
filling can be normal to decreased.
Interruption of the peripheral reflex arc (injury distal to the spinal cord): NGB
dysfunction in this situation may be similar to what occurs with distal spinal cord or
nerve root injury. Detrusor arreflexia is usually present and may lead to low

compliance. The smooth sphincter is likely incompetent, and the striated sphincter
may exhibit fixed residual tone that cannot be relaxed voluntarily. Sensation to
bladder filling can be normal to decreased.

4 Post-micturition Symptoms
Post-micturition symptoms (a feeling of incomplete emptying following urination and
post-micturition dribble) are infrequently reported in isolation of other LUTS.
Post-micturition symptoms have been grouped with voiding symptoms in women in the
IUA/ICS classification for standardized reporting.(Haylen et al., 2010) In men, post-void
dribbling accounted for much of post-micturition symptoms, whereas in women,
incomplete emptying was more common. (Maserejian et al., 2011)
Postvoid dribbling refers to involuntary leakage of urine immediately after voiding.
This may be seen in posttoilet-trained girls who dribble soon after standing up
following a void and are otherwise normal with no other associated urinary symptoms.
In these circumstances it may be a result of vesicovaginal reflux whereby urine is
trapped in the vagina during voiding, and once the child stands the urine begins to
dribble out. When in doubt, it can be confirmed by performing a micturating
cystourethrogram. (Wein, 2011a)

References
DeLancey JO (1994). Structural support of the urethra as it relates to stress urinary
incontinence: the hammock hypothesis. Am J Obstet Gynecol 170(6): 1713-1720;
discussion 1720-1713.
Dorsher PT, McIntosh PM (2012). Neurogenic bladder. Adv Urol 2012: 816274.
Fowler C, Kirby RS (1986). Electromyography of urethral sphincter in women with urinary
retention. The Lancet 327(8496): 1455-1457.
Fowler CJ, Kirby RS, Harrison MJ (1985). Decelerating burst and complex repetitive
discharges in the striated muscle of the urethral sphincter, associated with urinary retention
in women. Journal of Neurology, Neurosurgery & Psychiatry 48(10): 1004-1009.
Ginsberg D (2013). The epidemiology and pathophysiology of neurogenic Bladder. Am J
Manag Care 19: S191-196.
Haylen BT, de Ridder D, Freeman RM, Swift SE, Berghmans B, Lee J, et al. (2010). An
International Urogynecological Association (IUGA)/International Continence Society (ICS)
joint report on the terminology for female pelvic floor dysfunction. Neurourol Urodyn 29(1):
4-20.
Maserejian NN, Kupelian V, McVary KT, Doshi M, Link CL, McKinlay JB (2011). Prevalence
of post-micturition symptoms in association with lower urinary tract symptoms and
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Meng E, Lin W-Y, Lee W-C, Chuang Y-C (2012). Pathophysiology of Overactive Bladder.
LUTS: Lower Urinary Tract Symptoms 4: 48-55.
Padmanabhan P, Rosenblum N (2008). Chapter 16 - Idiopathic urinary retention in the
female. In: Raz S, Rodrguez LV (ed)^(eds). Female Urology (Third Edition), edn.
Philadelphia: W.B. Saunders. p^pp 187-193.
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Failure to Store
Because of the bladder
Overactivity
Involuntary contractions
Neurologic disease or injury
Bladder outlet obstruction (myogenic)
Inflammation
Idiopathic cause
Decreased compliance
Neurologic disease or injury
Fibrosis
Idiopathic cause
Combination of overactivity and decreased compliance
Hypersensitivity
Inflammation or infection
Neurologic disease or injury
Psychological origin
Idiopathic cause
Because of the outlet
Genuine stress urinary incontinence
Lack of suburethral support
Pelvic floor laxity or hypermobility
Intrinsic sphincter deficiency
Neurologic disease or injury
Fibrosis
Combination of causes
Failure to Empty
Because of the bladder
Neurologic cause
Myogenic cause
Psychogenic cause
Idiopathic cause
Because of the outlet
Anatomic causes
Pelvic organ prolapse
Urethral stricture
Urethral compression
Functional causes

Bladder neck dysfunction

Detrusor external sphincter dyssynergia
Dysfunctional voiding
Combination of causes
Idiopathic causes (e.g., Fowler's syndrome)

Table 1: Expanded functional classification of lower urinary tract dysfunction. Modified from
Wein A, Moy M : Categorization of voiding dysfunction. In: Raz S, Rodrguez LV. Female
urology. 3rd ed. Philadelphia: Elsevier Saunders; 2008, 162