NORMAL LOWER URINARY TRACT FUNCTION

Two-Phase Concept of Function: Filling or Storage and Emptying or Voiding

Whatever disagreements exist regarding the anatomic, morphologic, physiologic, pharmacologic, and mechanical details involved in the storage and expulsion of urine by the lower urinary tract, most experts agree on certain points.¹ The first is that the micturition cycle involves two relatively discrete processes: bladder filling with urine storage and bladder emptying. The second is that, whatever the details involved, these processes can be summarized from a conceptual point of view as follows.

Bladder filling and urine storage require the following:

1. Accommodation of increasing volumes of urine at a low intravesical pressure and with appropriate sensation

2. A bladder outlet that is closed at rest and remains so during increases in intra-abdominal pressure

3. Absence of involuntary bladder contractions

Bladder emptying requires the following:

1. Coordinated contraction of the bladder smooth musculature of adequate magnitude and duration

2. Concomitant lowering of resistance at the level of the smooth and striated sphincter

3. Absence of anatomic (as opposed to functional) obstruction

The smooth sphincter refers to the smooth musculature of the bladder neck and proximal urethra. This is a physiologic but not an anatomic sphincter and one that is not under voluntary control. The striated sphincter refers to the striated musculature, which is a part of the outer wall of the proximal urethra in males and females (this portion is often referred to as the intrinsic or intramural striated sphincter), and the bulky skeletal muscle group that surrounds the urethra at the level of the membranous portion in the male and the middle segment in the female (often referred to as the extrinsic or extramural striated sphincter). The extramural portion is the classically described external urethral sphincter and is under voluntary control.²

Any type of voiding dysfunction must result from an abnormality of one or more of the factors just listed. This two-phase concept of micturition, with the three components of each, related to the bladder or to the outlet provides a logical framework for a functional categorization of all types of voiding dysfunction and disorders of filling and storage or to voiding (Boxes 13-1 and 13-2). Some types of voiding dysfunction represent combinations of filling with storage and voiding abnormalities. Within this scheme, however, these become readily understandable, and their detection and treatment can be logically described. Various aspects of physiology and pathophysiology are always related more to one phase of micturition than another. All aspects of urodynamic and video-urodynamic evaluation can be conceptualized in this functional manner according to what they evaluate in terms of bladder or outlet activity during filling with storage or voiding (Table 13-1). All known treatments for voiding dysfunction can be classified in the broad categories of whether they facilitate filling with storage or voiding and whether they do so by an action primarily on the bladder or on one or more of the components of the bladder outlet (see Box 13-2 and Table 13-1).

Box 13-1 Functional Classification

Failure to store

Because of the bladder

Because of the outlet

Failure to empty

Because of the bladder

Because of the outlet

Box 13-2 Expanded Functional Classification

Table 13-1 Urodynamics Simplified

Phase Assessed^*	Bladder Assessment	Outlet Assessment
Filling and storage phase	Total P_ves and P_det during a filling cystometrogram	Urethral pressure profilometry
	Detrusor leak point pressure	Valsalva leak point pressure
	Detrusor leak point pressure	Fluoroscopy
Emptying phase	Total P_ves and P_det during a voiding cystometrogram	Micturitional urethral pressure profilometry
		Fluoroscopy
		Electromyography of periurethral striated musculature
	Flowmetry^†	Flowmetry^†
	Residual urine^†	Residual urine^†

P_det, detrusor pressure; P_ves, bladder pressure.

* This functional conceptualization of urodynamics categorizes each study according to whether it examines bladder or outlet activity during the filling and storage phase or emptying phase of micturition.

† In this scheme, uroflow and residual urine integrate the activity of the bladder and the outlet during the emptying phase.

Mechanisms Underlying the Two Phases of Function

This section summarizes pertinent points regarding the physiology of the various mechanisms underlying normal bladder filling with storage and voiding, abnormalities of which constitute the pathophysiologic mechanisms of the various types of dysfunction of the lower urinary tract. The information is consistent with that detailed by de Groat and associates,^3,⁴ Zderic and colleagues,² and Steers,⁵ and references are provided only when particularly applicable.

Bladder Response during Filling

The normal adult bladder response to filling at a physiologic rate is an almost imperceptible change in intravesical pressure. During at least the initial stages of bladder filling, after unfolding of the bladder wall from its collapsed state, this very high compliance (Δ volume/Δ pressure) of the bladder primarily results from its elastic and viscoelastic properties. Elasticity allows the constituents of the bladder wall to stretch to a certain degree without any increase in tension. Viscoelasticity allows stretch to induce a rise in tension, followed by a decay (i.e., stress relaxation) when the filling (i.e., stretch stimulus) slows or stops. Brading and colleagues ⁶ think there is continuous contractile activity in the smooth muscle cells to adjust their length during filling but without (normally) synchronous activity that would increase intravesical pressure, would impede filling, and could cause urinary leakage. Clinically and urodynamically, the bladder seems relaxed. The urothelium also expands but must preserve its barrier function while doing so. There may be an active component to the storage properties of the bladder. The mucosa and lamina propria are normally the most compliant layers of the bladder. Coplen and associates⁷ have hypothesized that the smooth muscle layer may have a chronic effect on compliance in the midportion of the cystometric filling curve through a complex interaction between muscle and extracellular matrix. This layer may acutely affect compliance in response to neurologic input as well.

In the usual clinical setting, filling cystometry seems to show a slight increase in intravesical pressure, but Klevmark ^8,⁹ elegantly showed that this pressure rise is a function of the fact that cystometric filling is carried out at a greater than physiologic rate and, at physiologic filling rates, there is essentially no rise in bladder pressure until bladder capacity is reached.

The viscoelastic properties of the stroma (i.e., bladder wall less smooth muscle and epithelium) and the urodynamically relaxed detrusor muscle account for the passive mechanical properties and normal bladder compliance seen during filling. The main components of the stroma are collagen and elastin. When the collagen component increases, compliance decreases. This can occur with various types of injury, chronic inflammation, bladder outlet obstruction, and neurologic decentralization. After decreased compliance has occurred because of a replacement by collagen of other components of the stroma, it is generally unresponsive to pharmacologic manipulation, hydraulic distention, or nerve section. Most often, under those circumstances, augmentation cystoplasty is required to achieve satisfactory reservoir function.

Does the nervous system affect the normal bladder response to filling? At a certain level of bladder filling, spinal sympathetic reflexes facilitatory to bladder filling and storage are evoked in animals, a concept developed over the years by de Groat and associates,³ who have also cited indirect evidence to support such a role in humans. This inhibitory effect is likely mediated primarily by sympathetic modulation of cholinergic ganglionic transmission. Through this reflex mechanism, two other possibilities exist for promoting filling and storage. One is neurally mediated stimulation of the predominantly α-adrenergic receptors in the area of the smooth sphincter, the net result of which would be to cause an increase in resistance in that area. The second is neurally mediated stimulation of the predominantly β-adrenergic receptors (inhibitory) in the bladder body smooth musculature, which would cause a decrease in bladder wall tension. McGuire and colleagues¹⁰ also cited evidence for direct inhibition of detrusor motor neurons in the sacral spinal cord during bladder filling that results from increased afferent pudendal nerve activity generated by receptors in the striated sphincter. Good evidence exists to support a tonic inhibitory effect of other neurotransmitters on the micturition reflex at various levels of the neural axis. Bladder filling and consequent wall distention may also release autocrine-like factors (e.g., nitric oxide, prostaglandins, peptides) that influence contractility.

Outlet Response during Filling

There is a gradual increase in urethral pressure during bladder filling, contributed to by at least the striated sphincteric element and perhaps by the smooth sphincteric element as well. The rise in urethral pressure seen during the filling and storage phase of micturition can be correlated with an increase in efferent pudendal nerve impulse frequency and in electromyographic activity of the periurethral striated musculature. This constitutes the efferent limb of a spinal somatic reflex, the so-called guarding reflex, which results in a gradual increase in striated sphincter activity.

Although it seems logical and compatible with neuropharmacologic, neurophysiologic, and neuromorphologic data to assume that the muscular component of the smooth sphincter also contributes to the change in urethral response during bladder filling, it is extremely difficult to prove this experimentally or clinically. The direct and circumstantial evidence in favor of such a hypothesis has been summarized by Wein and Barrett,¹ Elbadawi,¹¹ and Brading.¹² The passive properties of the urethral wall deserve mention because they undoubtedly play a large role in the maintenance of continence.^6,¹³ Urethral wall tension develops within the outer layers of the urethra; however, urethral pressure is a product of the active characteristics of smooth and striated muscle and of the passive characteristics of the elastic, collagenous, and vascular components of the urethral wall, because this tension must be exerted on a soft or plastic inner layer capable of being compressed to a closed configuration—the “filler material” representing the submucosal portion of the urethra. The softer and more plastic this area is, the less pressure required by the tension-producing area to produce continence. Whatever the compressive forces, the lumen of the urethra must be capable of being obliterated by a watertight seal. This mucosal seal mechanism explains why a thin-walled rubber tube requires less pressure to close an open end when the inner layer is coated with a fine layer of grease than when it is not, and the latter case is much like scarred or atrophic urethral mucosa.

Voiding with a Normal Bladder Contraction

Although many factors are involved in the initiation of micturition, intravesical pressure producing the sensation of distention is primarily responsible for the initiation of voluntarily induced emptying of the lower urinary tract in adults. Although the origin of the parasympathetic neural outflow to the bladder, the pelvic nerve, is in the sacral spinal cord, the organizational center for the micturition reflex in an intact neural axis is in the brainstem, and the complete neural circuit for normal micturition includes the ascending and descending spinal cord pathways to and from this area and the facilitatory and inhibitory influences from other parts of the brain.

The final step in voluntarily induced micturition involves inhibition of the somatic neural efferent activity to the striated sphincter and an inhibition of all aspects of any spinal sympathetic reflex evoked during filling. Efferent parasympathetic pelvic nerve activity is ultimately responsible for a highly coordinated contraction of the bulk of the bladder smooth musculature. A decrease in outlet resistance occurs, with adaptive shaping or funneling of the relaxed bladder outlet. Besides the inhibition of any continence-promoting reflexes that have occurred during bladder filling, the change in outlet resistance may also involve active relaxation of the smooth sphincter area through a nonadrenergic, noncholinergic mechanism, probably mediated by nitric oxide. The adaptive changes that occur in the outlet in part result from the anatomic interrelationships of the smooth muscle of the bladder base and proximal urethra (i.e., longitudinal smooth muscle continuity). Other reflexes that are elicited by bladder contraction and by the passage of urine through the urethra may reinforce and facilitate complete bladder emptying. Superimposed on these autonomic and somatic reflexes are complex, modifying supraspinal inputs from other central neuronal networks. These facilitatory and inhibitory impulses, which originate from several areas of the nervous system, allow for the full conscious control of micturition in the adult.

Urinary Continence during Abdominal Pressure Increases

During voluntarily initiated micturition, the bladder pressure becomes higher than the outlet pressure, and certain adaptive changes occur in the shape of the bladder outlet, with consequent passage of urine into and through the proximal urethra. Why do such changes not occur with increases in intravesical pressure that are similar in magnitude but that are produced only by changes in intra-abdominal pressure, such as straining or coughing? A coordinated bladder contraction does not occur in response to such stimuli, emphasizing the fact that increases in total intravesical pressure are by no means equivalent to emptying ability. Normally, for urine to flow into the proximal urethra, there be an increase in intravesical pressure; the increase must be a product of a coordinated bladder contraction, occurring through a neurally mediated reflex mechanism; and it must be associated with characteristic conformational and tension changes in the bladder neck and proximal urethral area.

Assuming that the bladder outlet is competent at rest, a major factor in the prevention of urinary leakage during increases in intra-abdominal pressure is the fact that there is at least equal pressure transmission to the proximal urethra during such activity. This phenomenon was first described by Enhorning ¹⁴ and has been confirmed in virtually every urodynamic laboratory since then. Failure of this mechanism, generally associated with hypermobility of the bladder neck and proximal urethra (another way of describing pathologic descent with abdominal straining), is an almost invariable correlate of genuine stress urinary incontinence in the female. No such hypermobility occurs in the male. The increase in urethral closure pressure that is seen with increments in intra-abdominal pressure normally exceeds the intraabdominal pressure increase, indicating that active muscular function due to a reflex increase in striated sphincter activity or other factors that increase urethral resistance, in addition to simple transmission of pressure, is also involved in preventing such leakage. Tanagho¹⁵ was the first to provide direct evidence of this.