Anatomy of the Lower Urinary Tract

The urinary, genital and intestinal tracts in women are inextricably linked in terms of anatomical support. A disorder of one of these tracts must therefore be considered in terms of its influence on surrounding structures and the functional anatomy of the pelvic floor (Wall, 1997).

Figure X1 | The lower urinary tract in men and women

Thus, although the anatomy of the lower urinary tract is complex, with the bladder and urethra normally acting as a single reciprocal functional unit, the function of the bladder is relatively simple: storage and elimination of urine in an effortless, painless manner, and without leakage (Wall, 1997).

Essentially, the bladder is a hollow sac comprising several layers, one of which is the detrusor musclue—a complex network of smooth muscle and connective tissue that accounts for bladder contractility (Figure X1). The bladder is also an autonomic viscus body under voluntary control and has complex neurophysiological aspects to its function (Wall, 1997).

Normally, extrinsic and intrinsic factors combine to maintain urethral closure. Extrinsic factors, such as the levator ani muscles, endopelvic fascia, and their attachments to the side wall of the urethra and pelvic cavity, form a ‘hammack’ behind the urethra (Figure X2).

When intra-abdominal pressure increases (during coughing, sneezing or exercise), the urethra is forced to close against the posterior hammock. However, if this support mechanism is weakened, the urethra and bladder neck may become hypermobile, leading to stress incontinence in many women (Wall, 1997).

Figure X2 | Diagrammatic representation of the ‘hammock hypothesis’ for posterior support of the urethra during episodes of raised intra-abdominal pressure (during coughing, sneezing, exercise) and, therefore, for prevention of urinary leakage (i.e. stress incontinence) (Wall, 1997). The arrow indicates the direction of downward urethral compression against the posterior hammock of support structures when intra-abdominal pressure increases.

Several intrinsic factors contribute to normal urethral closure, including the following two (Wall, 1997):

1. Maintenance of Urethral Tone

This is mediated by α-adrenoceptors in the sympathetic nervous system, probably at the level of the pelvic ganglia, with subsequent cholinergic innervations of longitudinally arranged smooth muscle in the urethra (Abrams 1993).

2. Intramural and Periurethral Striated Muscle

Bundles of the intramural muscle are present close to the urethral lumen (Figure X1), often intermingling with smooth muscle fibres, whereas the periurethral striated muscle (such as the pelvic floor) is separated from the urethra by a layer of connective tissue and is histologically and histochemically different from its intramural counterpart. Both types of striated muscle are innervated from S₂ to S₄ sacral segments of the spinal cord (Abrams 1993).

Stress incontinence Opens in new window resulting from altered intrinsic urethral factors is generally more difficult to correct than that caused by disorders of extrinsic factors (Jackson 1997). Although all of the above anatomical considerations are more relevant to stress than overactive urge incontinence, issues such as detrusor instability that are more pertinent to overactive urge incontinence, are discussed below.

Neurophysiology of Micturition

The normal storage and elimination of urine depends on neural pathways located in the brain, spinal cord and peripheral ganglia. Indeed, integration of somatic and autonomic efferent pathways in the lumbosacral spinal cord required for micturition, and many of the central pathways—together with peripheral and higher central—exhibit phasic or ‘switch-like’ patterns of activity (Harrison 1994).

Such complex sequences of neural facilitation and inhibition lead to coordination of activity between the sphincter apparatus of the bladder outlet with that of the detrusor muscle (Wall 1997; Resnick and Yalla 1997; DeLancey 1994; Harrison and Abrams 1994).

Bladder Filling

Urine, formed in the kidneys, enters the bladder from the ureters at a rate of 0.5–5.0 ml/min. While filling, the pressure in the bladder (intravesical pressure) is generally low and reasonably constant as the viscus expands to accept urine (Wall, 1997). It is largely the elastic and viscoelastic nature of the bladder wall, and neural activity, which inhibits detrusor contraction (Andersson 1997).

To maintain continence during bladder filling, intraurethral pressure must be greater than intravesical pressure and, indeed, an increase in outlet resistance occurs at this stage of the bladder ‘cycle’ (DeLancey 1994). This is attributable to increased muscle fiber recruitment in striated muscle in the urethra and pelvic floor (Wall 1997).

After the bladder has filled to a ‘threshold’ volume, usually about half of its physiological capacity, tension-stretch receptors are stimulated in the bladder wall. Signals are then sent to the pontine micturition center (Barrington’s nucleus) in the brain stem, mainly via small myelinated afferent nerve fibers (A δ) in the pelvic nerves, and then via an ascending ‘arm’ of a long spino-bulbo-spinal reflex pathway (Morrison 1997; Van Arsdalen and Wein 1991).

Cortical and diencephalic mechanisms then inhibit activity in the pontine micturition center (Figure X3) until a suitable time and place for micturition has been selected (Wall 1997; Resnick and Yalla 1997; Harrison and Abrams 1994; Morrison 1997).

Importantly, the bladder threshold volume at which tension-stretch receptors are excited is not fixed. It varies depending on activity in sensory afferents from the bladder, colon, rectum and perineum, and on activity in higher centers of the central nervous system (CNS) (Wall 1997). Furthermore, besides A δ afferents in the pelvic nerves, small unmyelinated C-fibres in these nerves conduct impulses from tension and nociceptors in the bladder wall; a substantial proportion of C-fibres may respond to chemical irritation of the bladder mucosa, rather than to distention of the bladder wall (Harrison and Abrams 1994; Morrison 1997).

Bladder Emptying

When urination starts, the intramural and periurethral (pelvic floor) striated muscle and external urethral sphincter voluntarily relax, the bladder neck opens and forms a funnel, and sustained contraction of the detrusor muscle ensues. The bladder is emptied, after which the detrusor muscle relaxes, the urethra re-close; intraurethral pressure increases and intravesical pressure falls in such a way that any urine in the proximal urethra is returned to the bladder, with filling and then restarting. Thus, as already indicated, micturtion is achieved by a complex neural coordination of muscular activity in the bladder outlet (Resnick and Yalla 1997; DeLancey 1994).

Micturition Reflexes

Afferent ‘limbs’ of the principal micturition reflex, a long spino–bulbo– spinal reflex, were described above. These, together with their efferent counterparts, are discussed in greater detail here.

Essentially, the CNS controls lower urinary tract function through a complex series of reflex mechanisms (Burnstock 1985). The major CNS structures involved are the cerebral cortex, brain stem (pontine micturition center) and sacral spinal cord (segments S2–S4; that is the sacral micturition center in the conus medullaris); the latter is where final integration of urethral and bladder activity occurs (Abrams 1993).

The pontine micturition center—controlled by impulses from cortical and diencephalic regions, is thought to be the region with voluntary control over micturition. Facilitative activity in the upper cortex allows the pontine micturition center to send efferent impulses down complex spinal pathways to the sacral micturition center, where impulses triggering detrusor contraction and external urethral sphincter relaxation are generated.

In addition, multiple neural connections between the cerebellum and brainstem reflex centers (Figure X3) are thought to coordinate detrusor contraction with pelvic floor relaxation (Wall 1997).

Peripheral innervations of the lower urinary tract is derived from three sources (Wall 1997; Harrison and Abrams 1994).

1. Sacral Parasympathetic (Pelvic) Nerves

These originate in segments S2–S4 of the spinal cord and control motor function of the bladder (that is, detrusor contraction and bladder emptying). Both pre- and post-ganglionic parasympathetic neurons release acetylcholine as their principal neurotransmitter, which acts as muscarinic receptors.

2. Thoracolumbar Sympathetic (Hypogastric and Sympathetic Chain) Nerves

These emanate from segments T11–L3 of the spinal cord; the main neuro-transmitter released by pre-ganglionic neurons is acetylcholine, whereas that released by post-ganglionic neurons is noradrenaline. The latter acts on δ-adrenoceptors in smooth muscle in the urethra and bladder neck causing contraction and acts on β-adrenoceptors in the smooth muscle of the bladder wall causing relaxation.

3. Sacral Somatic (Pudendal) Nerves

These cholinergic nerves are derived from segments S2–S4 of the spinal cord and innervate the external urethral sphincter and muscles of the pelvic floor.

The normal storage and elimination of urine involves complicated interaction between the sacral parasympathetic and thoracolumbar sympathetic systems outlined above (Figure X3).

Various neuropeptides (like neuropeptide Y) and non-adrenergic, non-cholinergic (NANC) neurotransmitters (like adenosine triphosphate [ATP]) are thought to play facilitatory and/or inhibitory roles in these peripheral systems, as well as in the spinal cord and higher regions of the CNS (Burnstock 1986; Daniel et al 1983; De Groat 1993). Simply put, however, the sympathetic nervous system mediates urine storage through detrusor relaxation and urethral contraction, whereas the parasympathetic nervous system mediates detrusor contraction and urination (Wang et al 1995).

Details of specific micturition reflexes involving the central and peripheral neural pathways are shown in simplified format, and discussed, in Figure X3. Fundamentally, spinal ‘guarding reflexes’ maintain continence during bladder filling whereas spino–bulbo–spinal reflexes are primarily responsible for urination (Table X1) (Harrison and Abrams 1994).

Receptor Pharmacology

Understanding of receptor pharmacology is obviously important since it is allied to information about the neural pathways involved in micturition reflexes. Detrusor smooth muscle cells contract through neural impulses mediated by acetylcholine muscarinic (M) receptors.

Although M₂/m2 receptors comprise about 80 per cent of the total population of muscarinic receptors in human smooth muscle (Andersson 1997), the bladder contains both M₂/m2 and M₃/m3 receptors, with the latter considered to mediate detrusor contraction (Nilvebrant et al 1997; Tobin and Sjygren 1995).

Presynaptic M₁ and M₂ receptors have also been identified in the bladder, with activation of M₁ subtypes perhaps facilitating the micturition cycle (Somogyi and De Groat 1992; Somogyi et al 1994; Yarker et al 1995).

Sympathetic supply to the detrusor muscle is meager, but noradenaline may facilitate bladder filling by relaxing the detrusor via stimulation of β-adrenoceptors contained in the muscle (Abrams 1993; Nilvebrant et al 1997).

Noradrenaline may also inhibit neurotransmission in parasympathetic ganglia. The bladder neck and proximal urethra receive a rich sympathetic supply, which, through stimulation of α-adrenoceptors, is involved in smooth muscle contraction and the maintenance of continence (Abrams 1993; Nilvebrant et al 1997).

Overall, however, much further research is required to fully define the role of various receptor subtypes located in the bladder and bladder ganglia, in the regulation of bladder function. While it is thought, for example, that acetylcholine is the principal neurotransmitter maintaining normal detrusor function, ATP may be a particularly important neurotransmitter to the detrusor muscle in patients with detrusor inastability or bladder outlet obstruction (Abrams 1993).