Connective Tissue

Several studies have demonstrated a role for connective tissue quality and pelvic floor dysfunction. identified that a mutated type I collagen gene is found in higher frequency among women with stress urinary incontinence. Such a connective tissue promoter of urinary incontinence is supported by finding that nulliparous women with stress urinary incontinence have significantly less collagen in their tissues relative to continent controls ( ). These authors further documented a decreased ratio of type I to type III collagen. This sort of evidence shows that apart from the muscles, connective tissues, and nerves, there are even more compositional differences between continent and incontinent women.

Bladder

During physiologic bladder filling, little or no increase in intravesical pressure is observed, despite large increases in urine volume. This process, called accommodation, is caused primarily by passive elastic and viscoelastic properties of the smooth muscle and connective tissue of the bladder wall. As filling increases to a critical intravesical pressure, detrusor muscle contractility probably is inhibited by activation of a spinal sympathetic reflex that results in inhibition of parasympathetic ganglionic transmission and stimulation of beta-adrenergic receptors in the bladder body. The net effect of these actions is filling and storage of urine within the bladder cavity, with little increase in intravesical pressure relative to volume. Abnormalities in the bladder wall, the detrusor muscle, or bladder innervation can result in incontinence (primarily detrusor overactivity, both idiopathic or neurogenic) or voiding dysfunction.

Urethra

Urethral Support

Anterior vaginal wall support directly affects urethral support as, except for lateral attachments of the urethra to the levator ani (pubourethral ligaments), the urethra rests on the anterior vaginal wall. The anterior vaginal wall is attached to the arcus tendineous fasciae pelvis (ATFP) that is a condensation of levator ani fascia arising from the surface of the levator ani muscles. The arcus tendineous levator ani is the point of attachment between the levator ani and the obturator internus muscles and lies just cranial to the ATFP.

The levator ani provides critical support to the pelvic organs, including the urethra. The urethra, vagina, and anus pass through the levator ani via the urogenital hiatus. This passage normally is closed via tonic contraction of the levator ani muscles. At baseline, the levator ani are contracted much like postural muscles of the spine. The effect of this contraction is to compress the midurethra, distal vagina, and rectum against the pubic bone distally and against abdominal hydrostatic pressure more proximally. The intention of pelvic floor exercises is to optimize this compressive effect on continence. The levator ani as a factor in urethral support is distinct from fascial-based urethral support mediated by the vaginal hammock. These relationships between the urethra, vagina, and levator ani is a reoccurring theme in understanding the mechanisms of female urinary continence.

Work by , and others, emphasized the need for intact support of the bladder neck and proximal urethra in a retropubic position for maintenance of urinary continence under stress. Urethral support by the anterior vaginal wall can be altered by defects in vaginal attachments to the levator ani at the ATFP, although, as noted earlier, the levator ani also contribute to urethral position. A stable suburethral layer of anterior vaginal wall along with tonic contraction of the levator ani prevents urethral and bladder neck descent and facilitates urethral compression with straining. The work by to document “transmission” of abdominal pressure to the urethra during periods of strain emphasized the importance of a retropubic urethra. The success of retropubic operations (i.e. Marshall–Marchetti–Krantz urethropexy) to correct urinary incontinence appeared to render additional support to the need for a retropubic urethra.

This concept is challenged, however, by the success of midurethral sling procedures that do not purpose a retropubic urethra. Sling surgery seems to emphasize the importance of a stable suburethral layer for effective urethral closure. To the contrary, a panel of experts viewing ultrasound videos of subjects’ urethral mobility during cough failed to find any predictive agreement as to which women had urinary incontinence. This and other studies mentioned later in this chapter challenge the importance of urethral support in female continence.

Additional, but less appreciated, elements of urethral support include the pubourethral ligaments that are lateral fascial and muscular attachments of the urethra to the levator ani. These structures, which are supportive of the female urethra and may contribute to urinary continence, are to be distinguished from the pubovesical muscles that probably play a role in voiding by opening the bladder neck. Pubovesical muscles can be seen during a retropubic dissection arching from the ATFP to insert on the urethra; they easily are confused with the pubourethral ligaments that lie beneath ( Fig. 15.1 ).

Retropubic space with the proximal urethra and vagina transected at a level just below the bladder, revealing the attachment of the vagina to the levator ani muscles. PVP, periurethral vascular plexus; R, rectum; VLA, vaginolevator attachment; VW, vaginal wall; PS, pubic symphysis; AFTP, arcus tendineus fasciae pelvis; ATLA, arcus tendineus levator ani; LA, levator ani muscles; OIF, obturator internus fascia; PVM, pubovesical muscle; U, urethra.

(From DeLancey JOL, Starr RA. Histology of the connection between the vagina and levator ani muscles: implications for urinary tract function. J Reprod Med . 1990; 35:765, with permission.)

Levator Ani

Recognition that the levator ani muscles can be made stronger with pelvic floor exercises and thereby improve female urinary continence has been known since before the 1950s. The levator ani muscles include the iliococcygeus, pubovisceral, and puborectalis muscles. The pubovisceral (also referred to as the pubococcygeus) muscle is composed of three subdivisions: the puboperineus (inserting into the perineal body), the pubovaginalis (inserting onto the vaginal wall), and the puboanalis (inserting into the intersphincteric groove of the anal canal). As noted, with contraction, the pubovisceral and puborectalis muscles close the urogenital hiatus and compress the urethra along with the rectum and vagina ( Fig. 15.2 ). This action renders a firm backboard for the urethra, particularly in light of the fascial attachments between the urethra (pubourethral ligament), vagina (ATFP), and the levator ani. As discussed in Chapter 2 , Chapter 4 , innervation of the levator ani does not come from the pudendal nerve. The nerve to the levator ani arises separately from S2-S4 and travels along the medial aspect of the levator muscles. It is therefore possible for a woman to have functional levator ani and a dysfunctional urethral sphincter.

Levator ani muscles in a contracted state, narrowing the pelvic opening, and supporting the pelvic organs.

(Reprinted with the permission of Cleveland Clinic.)

The levator ani and periurethral striated muscles (rhabdosphincter, compressor urethral, urethrovaginal sphincter) have a dual role in maintaining urinary continence: They provide resting urethral tone and assist in support (slow-twitch fibers), and they contract rapidly with increased intra-abdominal pressure (fast-twitch fibers). The integration of these two somatic muscle groups is vital to normal urinary control. During rapid increases in intra-abdominal pressure and with interruption of urination, there is voluntary and reflex periurethral striated muscle contraction, predominantly in the mid- and distal urethra, augmenting urethral pressure. Remarkably, demonstrated that urethral pressure spikes precede, and are often greater than, intravesical pressure spikes during coughing in continent women. Using cinefluorography, observed two actions when a woman is asked to interrupt her urine stream. The first is a prompt constriction of the voluntary musculature that immediately interrupts the urine stream in the midurethra, presumably due to periurethral striated muscle contraction against a stable suburethral base and levator plate. The urine distal to the constriction is voided, but the contents of the proximal urethra are forced back into the bladder. Simultaneously, the base of the bladder is seen to rise and is drawn cephalad presumably because of levator contraction acting on levator attachments to the suburethral base and bladder (i.e. anterior vaginal wall). Both of these actions are characteristic of voluntary fast-twitch muscle contraction; in fact, the diameter of fast-twitch muscle in the levator ani has been correlated with urethral pressures during periods of stress. Emphasizing the role of levator support, noted that pressure increases in the distal urethra with sneezing in dogs decrease after transecting the pelvic muscles from the urethra. Taken together, normal urinary continence in women relies on multiple redundant interconnected mechanisms.

Efferent and Afferent Pathways

Bladder smooth muscle is innervated primarily by parasympathetic nerves, while smooth muscle of the urethra and bladder neck are innervated by sympathetic nerves. Branches of the pudendal nerve innervate the skeletal muscles of the external urethral sphincter. These are the basic components of the efferent nerve pathways from the spinal cord to the lower urinary tract.

The parasympathetic nerves innervating the detrusor exit the spinal cord between S2 and S4. As with all parasympathetic nerves, the preganglionic neurotransmitter is acetylcholine (ACh) yet the postganglionic neurotransmitter varies with the target. Postganglionic parasympathetic neurotransmission to the urethral smooth muscle is via nitric oxide, while both ACh and adenosine triphosphate (ATP) serve this role to detrusor smooth muscle. The contribution of purinergic stimulation of the detrusor is likely minor under normal settings, although upregulation under certain conditions may contribute to development of an overactive bladder (O’Reilly et al., 2002). The role of nitric oxide in urethral smooth muscle contraction is inhibitory. Parasympathetic efferent stimulation of detrusor smooth muscle cells is mediated by muscarinic receptors of which there are two, M ₂ and M ₃ . Although the M ₂ receptor is the most abundant, the M ₃ receptor appears to preferentially drive detrusor contraction. These subtype variations are significant when considering the effects of anticholinergic medications on detrusor function.

The sympathetic nervous system acts to relax the bladder and contract the urethra. While sharing ACh as the preganglionic neurotransmitter with the parasympathetic system, postganglionic neurotransmission is via norepinephrine. Spinal cord input into the sympathetic control of the bladder arises from T10 to L2 with postganglionic delivery to the target organs via the hypogastric nerve. This nerve can be purposefully or inadvertently surgically transected (e.g. presacral neurectomy) with resultant overexpression of parasympathetic drive to the lower urinary tract.

Somatic nerve input to the lower urinary tract is primarily via the pudendal nerve that gets its spinal cord input from S2-S4. Motor neurons in spinal cord segments S2-S4 are located in Onuf’s nucleus. The neurotransmitter ACh acts on nicotinic receptors in the striated muscle of the external urethral sphincter.

Understanding of higher order control of urethral and bladder function has been enhanced greatly in recent years. The supraspinal elements of efferent control of the bladder are referred to as the pontine micturition and storage centers. These sites serve as the final integrative centers taking input from afferent spinal cord nerves and other regions of the brain ultimately acting to turn on or off the lower urinary tract. Central nervous system (CNS) excitatory neurotransmission is primarily via glutamic acid. The external urethral sphincter is activated via CNS glutamatergic transmission; suppression of this leads to urethral sphincter relaxation and voiding. Other supraspinal neurotransmitters that have garnered attention are serotonin and norepinephrine. As noted by , both serotonin and norephinephrine stimulate the urethral sphincter, potentiating the effect of glutamate-induced activation. Serotonine and norepinephrine reuptake inhibitors apparently are effective because of this enhancement in glutamate activation of the external urethral sphincter at Onuf’s nucleus. The prominence of serotonin and norepinephrine in the development of clinical depression renders some possible insight into the recognized association of depression and urinary incontinence.

The parasympathetic, sympathetic, and somatic efferent pathways also relay afferent sensory input from the lower urinary tract to the spinal cord and CNS. Parasympathetic sensory receptors (Aδ and C fibers) transmit information on both bladder volume during storage and contraction amplitude during voiding. These roles suggest that parasympathetic nerves both initiate voiding and sustain bladder contraction during voiding.

Coordinating Reflexes

The common view that urinary incontinence neatly divides into anatomic-based causes and detrusor overactivity fades with a more complete understanding of the coordination between the anatomy and underlying neurologic circuitry. Indeed proposed a singular abnormality in urethral motor function as the cause of stress and urge urinary incontinence. An overactive urethral opening mechanism wherein urethral pressure falls instead of increasing during periods of filling phase provocation was in their view the root cause of female urinary incontinence. This view emphasizes the coordination that exists between the bladder and urethra, which remains incompletely understood. It is appreciated that pathways between the CNS and the lower urinary tract interact such that as one is activated, another may be inhibited. Parasympathetic activation with detrusor contraction and consequent urethral relaxation leads to reflex inactivation of sympathetic and somatic contraction of the urethral sphincter. The guarding reflex is a good example of coordination of the various nervous system inputs to the lower urinary tract. As the bladder fills, stretch receptors relay afferent input to the spinal cord, where pudendal somatic efferent activation is stimulated. As the afferent stimulation increases with rising bladder volumes, the efferent stimulation to the external urethral sphincter likewise is increased to maintain continence. Meanwhile, detrusor contractile parasympathetic impulses are inactive with activation of sympathetic-driven detrusor relaxation and urethral smooth muscle contraction. Other sacral reflexes include a rise in urethral pressure preceding any rise in abdominal pressure, wherein that rise includes a proportional increase in pelvic floor activation. Taken together, there is abundant and growing evidence to argue that neuromuscular dysfunction, and not strictly altered anatomy, has a role in the development of female urinary incontinence.

This sort of complex integration of nervous system input to the lower urinary tract is inadequately measured by urodynamic studies. To what extent the autonomic nervous system is influencing detrusor and urethral sphincteric function cannot be measured. Because urethral resistance reflects not only any anatomic factors but also somatic and autonomic nervous system factors, the relative contribution of each is unknown. To assume that one factor is more important than another in causing urinary incontinence undoubtedly leads to the many treatments and to the variable treatment outcomes seen in clinical management.