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Platinum Priority – EditorialReferring to the article published on pp. 389–398 of this issue

Bladder Underactivity

Karl-Erik Andersson a,b,*

a Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston Salem, NC, USA; b Institute for Clinical Medicine, Aarhus University,

Aarhus, Denmark

Inability to completely empty the bladder is a common

clinical condition, particularly in the elderly, that has

recently evoked a renewed interest [1,2]. In this month’s

European Urology, Osman and colleagues summarize and

discuss the state of knowledge within this field [3].

1. Terminology

There are several terms used to describe impairment of

bladder emptying, but no consensus has been reached. One

of the terms used is detrusor underactivity (DU), which,

according to the International Continence Society (ICS), is

defined as a contraction of reduced strength and/or

duration, resulting in prolonged bladder emptying and/or

a failure to achieve complete bladder emptying within a

normal time span [4]. DU is a urodynamic diagnosis based

on a pressure–flow study and characterized by a low-

pressure, poorly sustained, or wavelike detrusor contrac-

tion with an associated poor flow rate [5]. This definition is

thus focused on detrusor contraction but covers only part of

the problem, which is multifactorial and may affect the

sensory (afferent) side of the micturition reflex, the central

nervous system (CNS) handling of the afferent information,

and the efferent side of the reflex, including nerves and the

detrusor muscle itself (Fig. 1). A urodynamic evaluation

does not identify these individual components.

Human urodynamic data suggest a loss of bladder

performance and voiding efficiency with aging, and the fact

that symptoms such as urinary retention, poor urinary

stream, and incontinence are age related indicates that

impaired voiding function has an age-associated prevalence

[6]. DU was found in nearly two-thirds of the incontinent

institutionalized elderly [3]. However, an age-related

DOI of original article: http://dx.doi.org/10.1016/j.eururo.2013.10.015.* Institute for Regenerative Medicine, Wake Forest University School of MeTel. +1 336 713 1195; Fax: +1 336 713 7290.E-mail address: Karl-Erik.Andersson@med.lu.se.

0302-2838/$ – see back matter # 2013 European Association of Urology. Phttp://dx.doi.org/10.1016/j.eururo.2013.11.005

decrease of detrusor contractility as the primary contributor

to impaired bladder emptying has not been conclusively

demonstrated [7] and requires in vitro studies on detrusor

muscle to be established.

As pointed out previously, reduced ability to empty the

bladder may result from disturbances of structures other

than the detrusor; thus, it seems illogical to use DU as a

general term. For the many disorders in which the common

denominator is an inability or a reduced ability to empty the

bladder, another term is preferable. Bladder underactivity

(BU) has been suggested [3], and this term may cover the

general condition irrespective of whether the cause is

afferent dysfunction, lack of CNS control, or the detrusor

itself. The term BU, then, may not exactly mirror the ICS

definition of detrusor overactivity, which is a strictly

urodynamic diagnosis.

Osman et al. suggested underactive bladder (UAB) to be

the equivalent of BU in terms of associated symptoms [3].

However, since UAB is based on symptoms, a better term

may be the UAB syndrome, in analogy with the ICS definition

of overactive bladder syndrome. Even so, as pointed out by

Osman et al. [3], UAB will have a certain vagueness, since

which symptoms should be included in the syndrome may

be discussed. As pointed out by several investigators,

BU/UAB syndrome and the potentially related condition of

detrusor hyperactivity with impaired contractility are

frustrating diagnoses for clinicians as well as patients,

since effective pharmacologic treatment is lacking [6,7].

2. Causes of bladder underactivity

Many diseases and disorders cause BU, and many of them

simultaneously engage not only sensory and CNS factors but

dicine, Medical Center Boulevard, Winston Salem, NC 27157, USA.

ublished by Elsevier B.V. All rights reserved.

[(Fig._1)TD$FIG]

Fig. 1 – Mechanisms involved in bladder underactivity.CNS = central nervous system.

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also the detrusor muscle. These causes include aging,

bladder outlet obstruction, diabetes mellitus, neurologic

disorders (eg, Parkinson disease, multiple sclerosis), injury

to the spinal cord and cauda equina (eg, herniated disc,

pelvic fractures), infectious neurologic problems (eg, AIDS,

herpes zoster infection), and iatrogenic factors (eg pelvic

surgery, radical prostatectomy).

Impaired detrusor contractility has been regarded as the

most common cause of BU—for example, in men with

bladder outflow obstruction—but its importance in, for

example, age-related voiding dysfunction is unclear [7].

Since detrusor contraction force and duration are a result of

efferent nerve activity, which in turn is dependent on

sensory input, impaired sensory function is a potential

cause of both BU and UAB syndrome. Afferent nerves from

the bladder convey the normal stimulus for activation of the

micturition reflex (ie, distension of the detrusor), which

initiates activity of low-threshold mechanoreceptive affer-

ents coupled in series with the detrusor muscle cells

(myogenic pathway). However, several functionally distinct

classes of bladder sensory neurons can be distinguished;

these stimuli, when applied to the urothelium, can initiate

afferent signals (urothelial pathway), including the normal

sensations of bladder filling, urgency, and nociception [8].

Structural and functional tissue changes accompanying

aging and diabetes, for example, may add to an altered

bladder afferent function, with subsequent reflex im-

pairment of voiding function. To optimize treatment, the

relative contributions of sensory afferent, CNS, and efferent/

myogenic factors to impaired voiding performance need to

be considered.

3. Animal models

Several models based on outflow obstruction, diabetes,

denervation, hydrodistension, and different types of in-

duced bladder damage have been used but are considered to

be of limited value [2]. Better animal models need to be

established to allow accurate testing of potential treat-

ments. Pelvic arterial occlusive disease plus vascular

endothelial dysfunction may cause progressive vascular

damage resulting in bladder dysfunction, proceeding from

bladder hyperactivity to BU [9,10], and models of chronic

bladder ischemia may be useful for identifying mechanisms

and targets for future treatment.

4. Treatment

The pharmacologic treatment options for BU/UAB syn-

drome are limited. Theoretically, the condition can

be improved by agents that increase detrusor contractile

activity and decrease bladder capacity and/or decrease

outlet resistance. Decreased detrusor contractile activity

as a cause of BU/UAB syndrome could result from partial

denervation and lack of contractile transmitters such

as acetylcholine and adenosine triphosphate and/or a lack

of tissue responsiveness. If the lack of tissue responsive-

ness is caused by irreversible changes in the bladder

wall (loss of muscle tissue, increased collagen deposition),

successful pharmacologic treatment is limited. Current

standard pharmacotherapy includes the use of muscarinic

receptor agonists such as bethechanol to stimulate

detrusor muscarinic receptors or cholinesterase inhibitors

such as distigmine to reduce the degradation of acetyl-

choline. However, available information shows that

little, if any, beneficial effect of muscarinic receptor

agonists or cholinesterase inhibitors can be obtained

in preventing or treating BU/UAB syndrome. Future

potential treatments, including gene and cell therapy,

are still at an experimental stage but have a certain

promise [10].

5. Future directions

The development of clinical noninvasive methods to

characterize the BU/UAB syndrome with different etiologies

and animal models for the study of pathophysiologic

mechanisms are urgently needed and will be rewarding.

Conflicts of interest: The author has been a consultant to Allergan,

Astellas, Ferring, and ONO.

References

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