504 CHAPTER 13 Neuropathic bladder

Physiology of urine storage and micturition

Urine storage

During bladder filling, bladder pressure remains low despite a substantial increase in volume. The bladder is thus highly compliant. Its high compliance is partly due to elastic properties (viscoelasticity) of the connective tissues of the bladder and partly due to the ability of detrusor smooth muscle cells to increase their length without any change in tension.

The detrusor is able to do this as a consequence of prevention of transmission of activity from preganglionic parasympathetic neurons to postganglionic efferent neurons—a so-called gating mechanism within the parasympathetic ganglia. In addition, inhibitory interneuron activity in the spinal cord prevents transmission of afferent activity from sensors of bladder filling.

Micturition

A spinobulbar-spinal reflex, coordinated in the pontine micturition center in the brainstem (also known as Barrington’s nucleus or the M region), results in simultaneous detrusor contraction, urethral relaxation, and subsequent micturition. Receptors located in the bladder wall sense increasing tension as the bladder fills (rather than stretch). This information is relayed, by afferent neurons, to the dorsal horn of the sacral cord. Neurons project from here to the periaqueductal gray matter (PAG) in the pons.

The PAG is thus informed about the state of bladder filling. The PAG and other areas of the brain (limbic system, orbitofrontal cortex) input into the pontine micturition center (PMC) and determine whether it is appropriate to start micturition.

At times when it is appropriate to void, micturition is initiated by relaxation of the external urethral sphincter and pelvic floor. Urine enters the posterior urethra and this, combined with pelvic floor relaxation, activates afferent neurons, which results in stimulation of the PMC, located in the brainstem.

Activation of the PMC switches on a detrusor contraction via a direct communication between neurons of the PMC and the cell bodies of parasympathetic, preganglionic motoneurons located in the sacral intermediolateral cell column of S2–4. At the same time that the detrusor contracts, the urethra (the external sphincter) relaxes.

The PMC inhibits the somatic motoneurons located in Onuf nucleus (the activation of which causes external sphincter contraction) by exciting GABA and glycine-containing, inhibitory neurons in the intermediolateral cell column of the sacral cord, which in turn project to the motoneurons in Onuf nucleus. In this way, the PMC relaxes the external sphincter.

Micturition is an example of a positive feedback loop, the aim being to maintain bladder contraction until the bladder is empty. As the detrusor contracts, tension in the bladder wall rises. The bladder wall tension receptors are stimulated and the detrusor contraction is driven harder.

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One of the problems of positive feedback loops is their instability. Several inhibitory pathways exist to stabilize the storage–micturition loop.

•Tension receptors activate bladder afferents, which, via the pudendal and hypogastric nerves, inhibit S2–4 parasympathetic motor nerve output. An ongoing detrusor contraction cannot be overridden.

•Afferents in the anal and genital regions and in the distribution of the posterior tibial nerve stimulate inhibitory neurons in the sacral cord, and these neurons inhibit S2–4 parasympathetic motor nerve output. This pathway can override an ongoing detrusor contraction. It is hypothesized that this system prevents involuntary detrusor contraction during sexual activity, defecation, and while walking, running, and jumping.

Excitatory neurotransmission in the normal detrusor is exclusively cholinergic, and reciprocal relaxation of the urethral sphincter and bladder neck is mediated by nitrous oxide (NO), released from postganglionic parasympathetic neurons.

506 CHAPTER 13 Neuropathic bladder

Bladder and sphincter behavior in the patient with neurological disease

A variety of neurological conditions are associated with abnormal bladder and sphincter function (e.g., spinal cord injury [SCI], spina bifida (myelomeningocele), MS). The bladder and sphincters of such patients are described as neuropathic. A discussion of bladder and sphincter problems and urinary incontinence in the patient without neurological disease can be found in Chapter 4.

Patients with neurological disease may have abnormal bladder function or abnormal sphincter function or, more commonly, both. The bladder may be overactive or underactive, as may the sphincter, and any combination of bladder and sphincter over or underactivity may coexist. “Activity” here means bladder and sphincter pressure.

In the normal lower urinary tract during bladder filling, the detrusor muscle is inactive and the sphincter pressure is high. Bladder pressure is therefore low and the high sphincter pressure maintains continence.

During voiding, the sphincter relaxes and the detrusor contracts. This leads to a short-lived increase in bladder pressure, sustained until the bladder is completely empty. The detrusor and sphincter thus function in synergy—when the sphincter is active, the detrusor is relaxed (storage phase), and when the detrusor contracts, the sphincter relaxes (voiding phase).

An overactive bladder (OAB) is a recently defined clinical disorder during which patients experience urgency with or without urge incontinence, usually accompanied by frequency and/or nocturia in the absence of causative infection or identified pathological conditions.

The bladder intermittently contracts during bladder filling, thus developing high pressures when normally bladder pressure should be low. In between these waves of contraction, bladder pressure returns to normal or near normal levels.

In a patient with an underlying neurological problem, bladder overactivity is commonly called detrusor hyperreflexia (DH) or neurogenic detrusor overactivity (NDO). Detrusor overactivity (DO) is a urodynamic observation characterized by involuntary detrusor (bladder muscle) contractions during bladder filling.

In other patients the bladder wall is stiffer than normal, a condition known as poor compliance. Bladder pressure rises progressively during filling; such bladders are unable to store urine at low pressures.

Some patients have a combination of DH and poor compliance. The opposite end of the spectrum of bladder behavior is the underactive bladder, which is low pressure during filling and voiding. This is called detrusor areflexia.

An overactive sphincter generates high pressure during bladder filling, but it also does so during voiding, when normally it should relax. This pathologic condition is known as detrusor-external sphincter dyssynergia (DESD, or detrusor sphincter dyssynergia [DSD]). DSD is always associated with detrusor overactivity, although NDO may occur with synergic sphincter function (i.e., without DSD).

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Pontine mesencephalic reticular formation is responsible for coordinating sphincter relaxation with detrusor contraction. Spinal cord lesions impair the transmission of coordinating influences from the pons during reflex detrusor contraction, and the uninhibited detrusor contraction stimulates a reflex sphincter contraction, resulting in bladder outflow obstruction.

See Fig. 13.1. During electromyographic (EMG) recording, necessary to diagnose DSD, activity in the external sphincter increases during attempted voiding (the external sphincter should normally be “quiet” during voiding). An underactive sphincter is unable to maintain enough pressure, in the face of normal bladder pressures, to prevent leakage of urine.

Figure 13.1 Detrusor-external sphincter dyssynergia (DSD) seen during videocystourethrography.