Download simplified neurophysiology of the lower urinary tract

ADDITIONAL ARTICLES
SIMPLIFIED
NEUROPHYSIOLOGY OF
THE LOWER URINARY TRACT
Lars Viktrup, MD, PhD, and Richard C. Bump, MD
Urinary incontinence is an important health problem with a significant effect on the quality of life of
its sufferers. Despite the prevalence and impact of the condition,
incontinent patients seem to accept their symptoms for years before they consult their physician.
When they do finally consult their
physician, an unnecessarily high
proportion is referred to a specialist. However, though the pathophysiology is complex, urinary incontinence can be effectively
treated in primary care practice
with a basic knowledge of the
anatomy and function of the lower
urinary tract. This review presents
updated findings on the neurophysiology of the lower urinary
tract (LUT), focusing on the role of
the central and peripheral autonomic and somatic nervous systems during urinary storage and
voiding. (Prim Care Update Ob/
Gyns 2003;10:261–264. © 2003
Elsevier Inc. All rights reserved.)
Lower urinary tract symptoms
(LUTS) and urinary incontinence in
particular affect the quality of life of
many men and women. Nevertheless, incontinent patients seem to
accept their symptoms for years before they consult their physician.1
Furthermore, for those who do consult their physician, an unnecessarily high proportion is referred to a
specialist for assessment and treatment.2 This is unfortunate, since
urinary incontinence may be manFrom Eli Lilly Research Laboratories, Indianapolis,
Indiana.
Volume 10, Number 5, 2003
aged in a primary care practice setting with reference to a basic description of the LUT. To maintain
urinary continence, intact anatomical structures in and around the
urethra together with a correct position of the bladder neck are a
necessity, while the comprehensive
innervation of the LUT needs to be
intact. The central and peripheral
autonomic and somatic nervous
systems synchronize urinary storage and voiding via inhibitory and
facilitatory activity. Certain neurotransmitters play an important role
in this function and new pharmacological opportunities to treat both
urge urinary incontinence (UUI)
and stress urinary incontinence
(SUI) are currently being investigated.3,4 A knowledge of the basic anatomy and function of the LUT is
important in understanding how
these medications can be effective.
The aim of this article is to provide
an updated simple review of the
neurophysiology of the LUT.
The Bladder and
the Urethral Muscles
The urinary bladder is a hollow,
muscular organ with smooth muscle fibers (detrusor muscle) extending in many directions, allowing it
to expand during urine storage and
contract during voiding. UUI is a
result of overactivity in this muscle.
The smooth muscle layer runs as a
continuum from the detrusor in the
bladder via the bladder neck and
ends in the proximal part of the
urethra. The urethral muscles may
© 2003 Elsevier Inc., all rights reserved. 1068-607X/03/$30.00
●
be divided into an inner layer of
smooth muscle fibers and an outer
layer of striated muscle fibers forming the rhabdosphincter (Figure 1).
The urethral smooth muscles are
primarily longitudinal and may
shorten and widen the urethral lumen during voluntary voiding,
while a thinner circular outer
sheath provides some resting tone
during storage. 5 The urethral
smooth muscle extends down most
of the length of the urethra. The
striated rhabdosphincter is thickest
in the middle two-thirds of the urethra, while the muscle proximally
and distally is horseshoe-shaped
and intermingled posterior with
connective tissue in the anterior
wall of the vagina.6
In addition to the muscular structures, the urethral lumen lining, the
urethral vascular plexus, and the
collagen and elastin connective tissue of the urethra contribute to continence. Another important factor
affecting SUI is the pelvic floor with
its levator ani and coccygeus muscle. The pelvic floor muscles are
suspended like a hammock between
the pubic bone in the front and the
coccyx bone behind. The pelvic
floor supports and maintains the
position of the pelvic organs and
attaches to the anterior vaginal wall,
allowing compression of the urethra
against the vaginal wall. These muscles help resist the tendency of the
bladder neck to thrust downward
when physical activities such as
running, jumping, coughing or
sneezing produce a sudden increase
in abdominal pressure. Conscious
tightening of these muscles helps
doi:10.1016/S1068-607X(03)00043-X
261
VIKTRUP AND BUMP
well as nociceptors. Injury to the
proprioceptive fibers of the pelvic
floor may account for some women’s decreased ability to perform
correct pelvic floor muscle training.8
Bladder Filling
Figure 1. The muscle types in the bladder, urethra, and the pelvic floor.
elevate and stabilize the anterior
vaginal wall and urethra.
The Central
Nervous System
Different centers in the brain and the
spinal cord have various roles for
the urinary function. The cerebral
cortex permits conscious control
over micturition by allowing voluntary contraction of the striated
rhabdosphincter and of the levator
ani muscle to resist micturition and
stress incontinence. It also provides
input to the pontine micturition
center in the brainstem to allow
voluntary suppression of detrusor
activity after early childhood. The
pontine micturition center coordinates the contraction of the detrusor
muscle and relaxation of the striated urethral rhabdosphincter during voiding. In the spinal cord, all
impulses reaching the bladder and
the urethra are mediated via nerves
originating in the thoracic-lumbar
sympathetic division and the sacral
parasympathetic and somatic divisions (Figure 2). The spinal cord
262
also serves as a relay station for
sensory information from the bladder, urethra, and the pelvic floor.
The Peripheral
Nervous System
The peripheral nervous system innervates the bladder and the urethra
with autonomic efferent sympathetic fibers via the hypogastric
nerve and the bladder with parasympathetic fibers to the bladder via
the pelvic nerve (Figure 2). The
somatic efferent motor innervation
to the striated rhabdosphincter runs
in the pudendal nerve, while direct
sacral fibers innervate the levator
ani muscle (Figure 2).7 The somatic
and sympathetic divisions promote
storage while the parasympathetic
division promotes voiding.
Sensory impulses from the bladder or the urethra travel back to the
spinal cord via the same sympathetic, parasympathetic, or somatic
nerves that supply the area with
efferent fibers. The sensory stimuli
include stretch-, tension-, friction-,
and proprioceptive receptors as
When the bladder begins to fill with
urine, stretch receptors in the bladder wall generate nerve impulses
that are transmitted along sensory
fibers to the central nervous system
(CNS). These afferent impulses
cause reflex activation of the sympathetic nucleus, a cluster of neurons located in the upper lumbar
spinal cord. The sympathetic nucleus responds by firing impulses
along the hypogastric nerve back to
the bladder and urethra, with subsequent release of the neurotransmitter norepinephrine. In the bladder the beta-adrenergic receptors on
the detrusor muscle respond to norepinephrine by causing relaxation
and allowing the bladder to fill
without an increase in pressure or
change in tone. At the same time
alpha1-adrenergic receptors in the
urethral smooth muscles respond to
norepinephrine by bringing about
contraction of the urethral smooth
muscles. During filling, there is also
tonic activity of the striated urethral
rhabdosphincter. This activity can
be augmented with voluntary contraction of the rhabdosphincter. As
the detrusor muscle relaxes and the
urethral smooth and striated muscles contract, the urethral pressure
remains greater than the bladder
pressure, facilitating urine storage
without urine loss.
Bladder Emptying
Normal voiding involves both voluntary and involuntary neural regulation. When the bladder reaches
capacity, stimuli from the bladder
are transmitted to the pontine micturition center. If voiding is initiPrim Care Update Ob/Gyns
LOWER URINARY TRACT
ing UUI by blocking the effect of
acetylcholine on muscarinie receptors on the detrusor muscle.
CONTRACTION OF
THE RHABDOSPHINCTER
Figure 2. The innervation of the bladder, urethra, and the pelvic floor.
ated, the pontine micturition center
stimulates output from the parasympathetic nucleus in the spinal
cord, which results in detrusor contractions via release of acetylcholine and stimulation of the muscarinic bladder receptors. The pontine
micturition center also sends impulses to the pudendal motor nucleus, which inhibits the activity of
the pudendal nerve and the rhabdosphincter. This combined activity allows the rhabdosphincter to
relax in coordination with the contraction of the bladder. Pontine impulses also suppress sympathetic
activity to the bladder and urethra.
The net effect is that bladder pressure increases due to contraction of
the detrusor muscle, while urethral
pressure decreases due to relaxation
of the rhabdosphincter, permitting
voiding to occur.
Volume 10, Number 5, 2003
Conscious Inhibition
of the Micturition Reflex
The cerebral cortex is the area of the
brain that mediates awareness and
conscious thought. Thus, the cerebral cortex is involved in the conscious perception of the need to
urinate and the decision to initiate
voiding. When the decision is made
to postpone bladder emptying, the
cerebral cortex: 1) sends signals to
the lower urinary tract to contract
the rhabdosphincter and levator
ani, to resist urination and urine
loss, and 2) suppresses parasympathetic impulses from the pontine
micturition center that normally
mediate micturition.
New and old pharmaceutical
agents have proved to alleviate premature detrusor contractions caus-
The rhabdosphincter and external
anal sphincter are innervated by the
pudendal nerve. The pudendal
nerve stimulates contraction of
these muscles via the neurotransmitter acetylcholine acting on nicotinic receptors. Nerve tracts from
higher centers in the central nervous system (the medulla and locus
ceruleus) terminate in Onuf’s nucleus in the spinal cord. These
nerves use serotonin and norepinephrine as their neurotransmitters. At Onuf’s nucleus they synapse with pudendal motor neurons.
The neurotransmitter glutamate
plays an important role for initiating the pudendal activity in Onuf’s
nucleus. Thus, there are three sets of
neurotransmitters involved—
serotonin, norepinephrine and glutamate, which are released in
Onuf’s nucleus, and acetylcholine,
which is released by pudendal neurons and which stimulates receptors on the rhabdosphincter and
external anal sphincter. In effect, 1)
glutamate starts the pudendal message, 2) serotonin and norepinephrine working at the proximal end of
the pudendal nerve by stimulating
its motor neuron cell bodies to amplify the message, while 3) acetylcholine works at the distal end of
the pudendal nerve where its release causes the rhabdosphincter to
contract. Increasing the pudendal
activity in Onuf’s nucleus causing
the rhabdosphincter to contract
more forcefully may avoid SUI if a
sudden increase in abdominal pressure occurs. Increasing the availability of norepinephrine and serotonin in Onuf’s nucleus is believed
to intensify this pudendal activity
and new pharmaceutical agents to
treat women with SUI are therefore
263
VIKTRUP AND BUMP
currently being tested for this purpose.9
CONTRACTION
OF THE PELVIC FLOOR
Direct sacral nerves carry impulses
mediated by acetylcholine to the
levator ani stimulating contraction
via nicotinic receptors.4
INHIBITION OF
PARASYMPATHETIC ACTIVITY
At the same time that the rhabdosphincter and levator ani are
stimulated to contract, inhibitory
impulses are transmitted along the
hypogastric nerve to inhibit contraction of the detrusor muscle.
The net effect of this neural activity is that urethral pressure increases with the contraction of the
rhabdosphincter and the levator
ani, while vesical pressure decreases with the relaxation of the
detrusor muscle. This keeps urine
contained in the bladder. After additional urine accumulates, the
micturition reflex occurs again. Al-
264
though the urge to urinate can usually be temporarily suppressed
again as more urine accumulates,
the urge sensations ultimately become irresistible and micturition
occurs.
6.
7.
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Doctor Guide to Urinary Incontinence in Women. London: Dorling
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Thind P. The significance of smooth
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Barber MD, Bremer RE, Thor KB,
Dolber PC, Kuehl TJ, Coates KW.
Innervation of the female levator ani
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Viktrup L. The risk of lower urinary
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We are grateful to Plexus Learning Design, LLC for the illustrations used in
Figures 1 and 2.
Address correspondence and reprint
requests to: Lars Viktrup, MD, PhD, Eli
Lilly and Company, Faris II, Drop Code
6112, Indianapolis, IN 46285.
Prim Care Update Ob/Gyns