Normal physiology  

Nervous System

1) Brain and spinal cord:

  • Normal voiding occurs in response to afferent signals of the bladder filling, and it is controlled by nervous system of the brain and spinal cord.
  • CNS and PNS coordinate the activity of the detrusor smooth muscle and urethral sphincter muscle.
  • The S2–S4 spinal cord constitute primary parasympathetic micturition center that innervate the bladder as well as the distal urethral sphincter (striated sphincter).
  • Above the sacral segments, the thoracolumbar segments (T11-L2) provide the sympathetic outflow from the spinal cord to the bladder and the proximal urethral sphincter.
  • Above the spinal cord is an important control center in the pons where it directly excites bladder neurons and inhibits the urethral sphincter, thus resulting coordination of the bladder contraction and sphincter relaxation at the same time to empty the urine.
  • The cerebral cortex appears to be involved in inhibiting lower centers of micturition.
  • Primary neurologic control of the bladder and urethral sphincters depends on multiple levels of the nervous system, especially the sacral segments and the pons

2) Peripheral innervation:

  • The lower urinary tract is innervated by three principal sets of peripheral nerves involving the parasympathetic, sympathetic, and somatic nervous systems from 3 major nerves, namely the pelvic, hypogastric and pudendal nerves, respectively.
  • These nerves contain afferent (sensory) as well as efferent (motor) axons.
  • Parasympathetic and sympathetic nervous systems form pelvic plexus at the lateral side of the rectum before reaching bladder and sphincter.
  • Division according to the system
    • Sympathetic pathways:
      • originate from the T11-L2 (sympathetic nucleus; intermediolateral column of gray matter)
      • inhibiting the bladder body and excite the bladder base and proximal urethral sphincter
    • Parasympathetic nerves:
      • emerge from the S2-4 (parasympathetic nucleus; intermediolateral column of gray matter)
      • exciting the bladder and relax the urethra
    • Sacral somatic pathways:
      • emerge from the S2-4 (Onuf’s nucleus; ventral horn)
      • form pudendal nerve, providing an innervation to the striated urethral sphincter.
      • Pudendal nerves from S2-4 excite the distal striated urethral sphincter.
  • Division according to the action
    • Efferent Action
      • Parasympathetic:
        • postganglionic neurons are located in the detrusor wall layer as well as in the pelvic plexus.
        • Releases the excitatory transmitter acetylcholine.
        • Activation (pelvic nerve) induces contraction of the bladder body, which contribute emptying of the bladder.
      • Sympathetic:
        • provides a noradrenergic excitatory and inhibitory input to the bladder and urethra.
        • Activation (hypogastric nerve) induces relaxation of the bladder body and contraction of the bladder outlet and urethra, which contribute urine storage in the bladder.
      • Sacral somatic nerve:
        • Activation (pudendal nerve) causes the contraction of the striated urethral sphincter.
    • Afferent Action
      • Afferent axons in the pelvic, hypogastric, and pudendal nerves also transmit sensory information from the lower urinary tract to the spinal cord.
      • Pelvic nerve afferents consist of the following 2 fibers:
        • Myelinated A-delta fibers:
          • mediating normal micturition
          • sensitive to gradual distention of the urinary bladder
        • Unmyelinated C-fibers:
          • Under normal conditions: do not respond to bladder distention.
          • Various pathological conditions including SCI: chemoreceptors and mechanosensitive nociceptors from the bladder and urethra become hyperactive and can cause hyperreflexic bladder and urinary incontinence.
  • Division according to the name of the nerves
    • Pelvic nerve:
      • Efferent
        • Parasympathetic
        • Axons from preganglionic neurons in the sacral spinal cord traverse the pelvic nerve and make synapses in the pelvic plexus.
        • postganglionic neurons are primarily cholinergic but they may also contain purinergic, peptidergic and nitrergic.
        • postganglionic neurons innervate detrusor smooth muscle
      • Afferent sensory
        • from detrusor smooth muscle
        • Neurotransmitters include glutamate, neuropeptides and nitric oxide.
    • Hypogastric nerve:
      • Sympathetic
      • postganglionic fibers are primarily noradrenergic but may also be purinergic and peptidergic
      • Innervating primarily longitudinal and circular smooth muscle layers in the bladder neck and proximal urethra with a minor component innervating the detrusor muscle
    • Pudendal nerve:
      • Efferent
        • Innervating the urethral rhabdosphincter as well as the external anal sphincter and some perineal muscles
        • Female levator ani muscle is not innervated by the pudendal nerve but rather by innervation that originates the sacral nerve roots (S3-S5) that travels on the superior surface of the pelvic floor (levator ani nerve) [Barber 2002].
      • Afferent sensory
        • from urethra as well as the rectum, clitoris or penis and perineal skin
        • contain glutamate and neuropeptides, similar to pelvic afferent fibers

Nervous Control of Micturition

1. Local Reflex Pathways

  • Reflexes between the urethra and bladder play an integral role in the neural control of the lower urinary tract

1-1. Storage reflex

  • Storage phase is regulated by 2 separate storage reflexes: sympathetic autonomic and somati

1) Sympathetic storage reflex:

  • Synonyms:
    • pelvic-to-hypogastric reflex
    • bladder-to-sympathetic reflex
  • Role: Primarily urine storage mechanism
    • (contracting the muscle) stimulating α1 adrenergic receptors in the urethral smooth muscle: -> promotes closure of the urethral outlet
    • (relaxing the muscle) stimulating β3 adrenergic receptors in the detrusor smooth muscle: -> inhibits neurally mediated contractions of the bladder by
  • Activation mechanism:
    • Reflex activation triggered by afferent activity induced by distention of the urinary bladder

2) Somatic storage reflex:

  • Synonyms:
    • pelvic-to-pudendal reflex
    • guarding reflex
    • continence reflex
    • bladder-to-external urethral sphincter guarding reflex
  • Role:
    • During normal urine storage this pathway is tonically active
    • A more rapid somatic storage reflex: during sudden unexpected increase in bladder pressure, it becomes dynamically active to contract the rhabdosphincter
  • Activation mechanism:
    • Triggered by a sudden increase in bladder pressure, such as during a cough, laugh or sneeze.
    • It activates striated urethral muscle.
  • Clinical meaning in SCI:
    • Inhibition of bladder activity during urine storage
    • Alterations in these mechanisms may develop in neurogenic bladder dysfunction.
    • Direct activation of these reflexes by electrical stimulation of the sacral spinal nerve roots (sacral neuromodulation) is proved to be clinically effective.
    • Is induced in SCI patients by activation of afferent input from various sites including the urethral sphincter, anal sphincter [McGuire 1983; Fossberg 1990], penis (penile squeeze; Kondo 1982], vagina, rectum and perineum.

1-2. Micturition Reflex

1) Somatic micturition reflex (urethra-to-bladder reflex)

  • Synonym:
    • excitatory urethra to bladder reflex
  • Activation mechanism:
    • In response to urethral fluid flow, sensory nerves in the wall of the urethra can fire [Talaat 1936]
    • is mediated by afferent inputs traveling through the pudendal nerve to the sacral spinal cord [Shefchyk 1998] and brain [Barrington 1941].
    • is thought to involve a spinobulbospinal pathway like the actions of bladder afferents [Morrison 1987]
  • Role:
    • Urinary flow through the urethra could alter the following vesicourethral activity:
      • Urinary bladder:
        • initiate bladder contractions in the quiescent bladder
        • augment bladder contractions already underway [Garry, 1959]
      • Urinary sphincter:
        • suppress sphincter activity (e.g. guarding reflex) during voiding

2) Spinal vesicovesical micturition reflex: Pathologic reflex

  • Synonym:
  • C-fiber bladder afferent to bladder efferent reflex
  • Activation mechanism
    • Triggered by certain noxious stimulus (bladder fullness is not a triggering stimulus) -> activated by bladder afferents unmyelinated C-fibers in the bladder wall -> major pelvic ganglion -> through pelvic nerve into the spinal cord -> spinal micturition center
    • Efferent fibers traverse (through pelvic nerve) and synapse in the major pelvic ganglion -> innervate the smooth muscle in the bladder wall -> bladder contraction
  • Role:
    • Pathologic parasympathetic micturition reflex responsible for detrusor hyperreflexia (for example, in SCI condition)
  • Clinical meaning in SCI:
    • Intravesical capsaicin instillation completely block rhythmic bladder contractions [De Groat, 1990]

2. Supraspinal Vesicovesical Micturition Reflex Pathway

  • The parasympathetic reflex outflow to the detrusor has a more complicated central organization, involving spinobulbospinal pathway passing through a micturition center in the pons.
  • Synonym:
    • Aδ-fiber bladder afferent to bladder efferent reflex
  • Activation mechanism
    • Triggered by stretch receptors in the detrusor muscle to the distention of the bladder -> activates myelinated Aδ afferent fibers (first order afferent neuron: through pelvic nerve) -> spinal cord
    • spinobulbospinal pathway (second order afferent neuron) -> activates neuron in the pontine micturition center (PMC; Barrington's nucleus; M region) -> this neuron project directly to reciprocal connections:
      • bladder preganglionic neurons in the sacral parasympathetic nucleus: -> Sacral parasympathetic preganglionic neuron (PGN) (first order efferent neuron; through pelvic nerve) -> Activation of pelvic parasympathetic postganglionic neurons (second order efferent neuron; pelvic plexus) and causes acetylcholine release to the M2 and M3 receptors -> bladder contraction
      • Nucleus in the sacral dorsal gray commissure (DGC) (GABA premotor interneuron) -> excite urethral sphincter motoneuron (first order efferent neuron) in Onuf's nucleus -> inhibits the urethral sphincter [Blok 1998]
  • Role: normal supraspinal, parasympathetic micturition reflex

3. Summary

  • Taken the functions of urinary bladder and urethral sphincter together:
    • In filling phase:
      • Bladder: should be stable and compliant
      • Urethral sphincter: should be able to resist increases in abdominal pressure and remain closed (competent)
      • Therefore, it should hold increasing amounts of urine at low pressure without involuntary contractions.
    • In emptying phase:
      • Urethral sphincter: initial relaxation before detrusor contraction by:
        • activation of a parasympathetic pathway (GABA interneuron)
        • removal of excitatory inputs to the urethra
        • flow of urine through the urethra facilitate bladder emptying
      • Bladder: contract to empty the urine without significant residual urine
 Storage phaseEmptying phase
Desired actionBladder: relaxation required
Sphincter: closed
Bladder: contraction required
Sphincter: relaxed

Key Points of This Section
  • Normal voiding occurs in response to afferent signals of the bladder filling, and it is controlled by nervous system of the brain and spinal cord.
  • The pons coordinates the activity of the detrusor smooth muscle and urethral sphincter muscle.
  • The S2–S4 spinal cord constitutes primary parasympathetic micturition center that innervate the bladder as well as the urethral sphincter.
  • The T11-L2 spinal segments provide the sympathetic outflow from the spinal cord to the bladder and the proximal urethral sphincter.
  • Central and local and reflexes play an important role in the neural control of the lower urinary tract.

References

  • Barber MD, Bremer RE, Thor KB, Dolber PC, Kuehl TJ, Coates KW. Innervation of the female levator ani muscles. Am J Obstet Gynecol. 2002 Jul;187(1):64-71.
  • Barrington FJF. The component reflexes of micturition in the cat III. Brain 1941;64:239–43.
  • Blok BF, van Maarseveen JT, Holstege G. Electrical stimulation of the sacral dorsal gray commissure evokes relaxation of the external urethral sphincter in the cat. Neurosci Lett. 1998 Jun 12;249(1):68-70.
  • de Groat WC, Kawatani M, Hisamitsu T, Cheng CL, Ma CP, Thor K, Steers W, Roppolo JR. Mechanisms underlying the recovery of urinary bladder function following spinal cord injury. J Auton Nerv Syst. 1990 Jul;30 Suppl:S71-7.
  • Fossberg E, Sorensen S, Ruutu M, Bakke A, Stien R, Henriksson L, Kinn AC. Maximal electrical stimulation in the treatment of unstable detrusor and urge incontinence. Eur Urol. 1990;18(2):120-3.
  • Gary RC, Roberts TD, Todd JK. Reflexes involving the external urethral sphincter in the cat. J Physiol. 1959 Dec;149:653-65.
  • Kondo A, Otani T, Takita T. Suppression of bladder instability by penile squeeze. Br J Urol. 1982 Aug;54(4):360-2.
  • McGuire EJ, Morrissey S, Zhang S, Horwinski E. Control of reflex detrusor activity in normal and spinal cord injured non-human primates. J Urol 1983 Jan; 129(1):197-9.
  • Morrison JFB. Reflex control of the lower urinary tract. In: Torrens M, Morrison JFB (eds). The Physiology of the Lower Urinary Tract, Springer-Verlag, New York, 1987;193–236.
  • Shefchyk SJ, Buss RR. Urethral pudendal afferent-evoked bladder and sphincter reflexes in decerebrate and acute spinal cats. Neurosci Lett. 1998 Mar 20;244(3):137-40.
  • Talaat M. Afferent impulses in the nerves supplying the urinary bladder. J Physiol 1936;89:1–13.

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