Storage and voiding depend on a coordinated reflex network from the bladder wall up to the brain. Understanding the anatomy, the autonomic/somatic innervation, and the reflexes that switch between storage and voiding is the foundation for classifying every lower-urinary-tract (LUT) dysfunction as a failure to store or a failure to empty, due to the bladder or the outlet.
Lower Urinary Tract Anatomy
- Bladder layers:
- Urothelium (~7 cells thick) — functions: (1) a relatively impermeable barrier (uroplakin and tight-junction proteins); (2) sentinel defense against uropathogens (uroplakins are the attachment site for type-1 piliated E. coli); (3) afferent signaling (urothelial cells release/respond to neurotransmitters via myofibroblasts); and (4) modulation of detrusor contractility. The glycosaminoglycan layer may aid bacterial anti-adherence but has no proven impermeability role.
- Lamina propria — a plexus of unmyelinated nerves, interstitial cells (myofibroblasts), and microvasculature.
- Detrusor — fascicles in random directions; gap junctions let excitation propagate through the smooth-muscle syncytium; has afferent innervation; contractility declines rapidly with ischemia.
- Internal (smooth) sphincter — a competent ring at the bladder neck in males (absent in females); a physiologic, not anatomic, sphincter, not under voluntary control.
- External (striated) sphincter (EUS): under voluntary control, innervated by the pudendal nerve (S2–S4), with slow-twitch fibers (sustained tone) and fast-twitch fibers (rapid tone for sudden pressure rises). Two parts: the periurethral pelvic-floor striated muscle (both fiber types; pelvic-floor exercises may convert fast- to slow-twitch) and the rhabdosphincter (predominantly slow-twitch, in the outer wall of the proximal urethra).
Smooth Muscle and Bladder Mechanics
- Contraction: parasympathetic acetylcholine acts on muscarinic receptors → Ca²⁺ entry → Ca²⁺-calmodulin activates myosin light-chain kinase → actin–myosin interaction; relaxation when intracellular Ca²⁺ falls. Interstitial cells/myofibroblasts may pace spontaneous activity.
- Storage (filling): compliance = ΔV/ΔP. Decreased compliance results from (1) viscoelastic changes — more collagen/less elastin (from injury, obstruction, denervation; once collagen-replaced, it is unresponsive to drugs/distention/nerve section and often needs augmentation), fast filling rate (slow physiologic filling keeps Pves <10 cm H₂O), and detrusor hyperactivity; or (2) central neural input. Types I, III, IV collagen predominate; type III especially associates with poor storage.
- Voiding: Pdet = Pves − Pabd. Low voiding pressure in women does not necessarily mean impaired contractility.
Neural Control
Micturition uses three nerves, all carrying efferent and afferent fibers: parasympathetic (pelvic, S2–S4), sympathetic (hypogastric, T11–L2), and somatic (pudendal, S2–S4).
- Parasympathetic (sacral S2–S4) — contributes to voiding: excites the bladder and relaxes the urethra. Cauda equina/pelvic plexus injury causes decentralization (not complete denervation).
- Sympathetic (T11–L2) — contributes to storage: relaxes the bladder (β-adrenergic), contracts the bladder base and urethra (α-adrenergic).
- Somatic (pudendal, S2–S4; motoneurons in the Onuf nucleus) — contributes to storage: contracts the EUS.
Afferents:
| Fiber type | Location | Normal function | Effect of inflammation |
|---|---|---|---|
| Aδ (finely myelinated) | Smooth muscle | Sense bladder fullness (wall tension) | Discharge at lower pressure threshold |
| C fiber (unmyelinated) | Mucosa | Stretch/volume sensing | Discharge at lower threshold |
| C fiber (unmyelinated) | Mucosa/muscle | Nociception to overdistention; silent afferent | Sensitive to irritants; becomes mechanosensitive, unmasking a new afferent pathway |
Pelvic-nerve afferents are most important for normal micturition. Modulators of afferent sensitivity include nitric oxide (major mediator of urethral smooth-muscle relaxation; PDE5 terminates NO action) and urothelial ATP release. Aging and diabetes reduce afferent sensitivity → impaired voiding and higher residuals.
- Pontine micturition center (PMC / Barrington nucleus): the essential control center integrating afferent input and coordinating sphincter relaxation with detrusor contraction; glutamate is its primary neurotransmitter. The PMC indirectly inhibits the Onuf nucleus via GABAergic interneurons.
Reflex Circuitry
- Storage (guarding) reflex — bladder distention → low-level Aδ afferent firing → sympathetic outflow (contract bladder base/urethra, relax bladder) and pudendal outflow to the EUS; parasympathetic is inactive.
- Voiding (spinobulbospinal) reflex — high-level afferent activity activates the PMC, which inhibits the guarding reflex and stimulates parasympathetic outflow (contract bladder, relax internal sphincter). The ascending signal travels pelvic nerve → periaqueductal gray → PMC → descending output. The reflex functions as an on/off switch; without higher control (infants, neuropathic bladder), involuntary emptying occurs at a critical volume.
- Emptying phase: initial urethral-sphincter relaxation (NO-mediated + withdrawal of sympathetic input), then bladder contraction and flow.
- Duloxetine (norepinephrine/serotonin reuptake inhibitor) increases both sphincter and bladder activity — used for stress and urgency incontinence.
- After spinal cord injury, a capsaicin-sensitive C-fiber spinal reflex develops and contributes to detrusor overactivity (also in MS); the research-only ice-water test is negative in healthy bladders but positive (cannot retain) when C-fiber reflexes dominate.
Classification of LUT Dysfunction
Normal storage requires low-pressure accommodation with normal sensation, a closed outlet, and no detrusor overactivity; normal emptying requires a coordinated detrusor contraction, lowered sphincter resistance, and no anatomic obstruction. Dysfunction is classified as failure to store or failure to empty, each due to the bladder or the outlet.
- Failure to store — from bladder overactivity (involuntary contractions and/or low compliance), decreased outlet resistance, or altered sensation.
- Bladder overactivity is most commonly seen with neurologic disease (CVA, MS, Parkinson are the top causes of urge UI via loss of suprapontine inhibition → neurogenic detrusor overactivity), BOO (BPH in men; post-anti-incontinence-surgery in women), iatrogenic radiation, aging, SUI, inflammation/irritation, and idiopathic causes. Diabetes causes NDO early and impaired emptying late.
- Decreased outlet resistance — from damage to sphincter innervation/structure or (in women) outlet support. Intrinsic sphincter deficiency is most often iatrogenic (radical prostatectomy is the most common surgical cause in men; urethral/anti-incontinence surgery in women), plus neurologic disease, lumbosacral injury, α-antagonist/relaxant drugs, and obstetric trauma.
- Failure to empty — from bladder underactivity (reduced magnitude/coordination/duration → overflow incontinence; from lumbosacral/conus disease, diabetic/alcoholic neuropathy, radical pelvic surgery) or increased outlet resistance (more common in men; anatomic obstruction or sphincter dyssynergia).
- ICS terms: overactive detrusor (neurogenic vs idiopathic); underactive detrusor (inadequate magnitude/duration); acontractile detrusor (no contraction on UDS); areflexia (acontractility from absent neural control); dysfunctional voiding (intermittent flow from periurethral striated contraction in neurologically normal patients); detrusor sphincter dyssynergia (detrusor contraction with involuntary striated-sphincter contraction); non-relaxing urethral sphincter obstruction (usually neurologic).
Self-Test
1. What are the functions of the urothelium? A barrier (uroplakin/tight junctions), sentinel defense against uropathogens, afferent signaling, and modulation of detrusor contractility.
2. How do fast- vs slow-twitch fibers contribute to continence? Slow-twitch fibers maintain sphincter tone over prolonged periods; fast-twitch fibers add tone rapidly (e.g. with a sudden rise in abdominal pressure).
3. Which nerve and roots innervate the EUS? The pudendal nerve, S2–S4 (motoneurons in the Onuf nucleus).
4. Describe the autonomic innervation and its roles in storage/voiding. Parasympathetic (pelvic, S2–S4) drives voiding (bladder contraction, urethral relaxation); sympathetic (hypogastric, T11–L2) drives storage (bladder relaxation, base/urethral contraction).
5. What is the primary neurotransmitter of the PMC stimulating micturition? Glutamate.
6. Describe the storage and voiding reflexes. Storage (guarding): Aδ afferents → sympathetic + pudendal outflow (close outlet, relax bladder). Voiding (spinobulbospinal): high afferent activity → PMC inhibits guarding and stimulates parasympathetic outflow (contract bladder, relax sphincter).
7. What is the first step of bladder emptying? Relaxation of the urethral sphincter (decreasing outlet resistance) before the detrusor contracts.
8. Which afferent fibers sense fullness vs nociception? Aδ fibers sense fullness (wall tension); C fibers sense nociception/overdistention.
9. What mediates urethral relaxation during voiding? Nitric oxide.
10. MOA and uses of duloxetine? A norepinephrine/serotonin reuptake inhibitor that increases sphincter and bladder activity — used for stress and urgency incontinence.
11. List aging-related changes to micturition. Decreased afferent (sensation) and efferent activity, decreased detrusor contractility, and decreased urethral pressure.