Bladder and Urethra
The bladder and upper urethra are composed of bundles of smooth muscle fibers arranged in a reticular lattice, the outermost bundles being more circular and the inner bundles more longitudinal in orientation at the bladder neck.1 The smooth muscle bundles blend into the striated muscle of the external urethral sphincter, which is derived from the pelvic diaphragm. The bladder is lined by transitional epithelium, which is sensitive to irritants such as bacterial toxins and various urinary crystals. The urethra and trigone are especially sensitive, and the presence of any irritant in these areas can create significant discomfort.
Proper function of the lower urinary tract depends on intact autonomic and somatic nervous innervation. The detrusor muscle of the bladder is innervated by both sympathetic and parasympathetic fibers. Storage functions are mediated by the sympathetic component, which arises from spinal levels T10–L1. The chemical mediator of this process is norepinephrine, which acts on β-adrenergic receptors in the fundus of the bladder and causes muscle relaxation for low-pressure storage of urine. The same sympathetic stimulus acts on the β-adrenergic receptors of the trigone, bladder neck, and proximal urethra to increase internal sphincter activity and promote continence during urine storage by maintaining outlet resistance. The external urinary sphincter, innervated by the pudendal nerve, progressively increases its tone as the bladder fills, providing additional resistance. As the child develops, the external sphincter may be consciously contracted at times of urgency or stress to prevent the unwanted passage of urine. Properly coordinated function of the external urinary sphincter relies on an intact sacral reflex arc which should be well developed in normal infants, but is variably functional in infants with spinal cord abnormalities or pelvic lesions.2,3
Spinal pathways connect the sacral micturition center with three areas in the brain stem, collectively referred to as the pontine micturition center.4 This center functions to inhibit urination during storage and to produce external sphincter relaxation during the voiding phase. Above this level are areas of cerebral cortex which oversee and modulate the autonomic process. It is the mature, integrated function of all these components that produces urinary continence.
Toilet training is, in large part, a learned phenomenon. It requires adequate recognition by the brain that micturition would be socially unacceptable in a given situation. With maturation, the bladder gains capacity, allowing for longer intervals between voiding. The approximate bladder volume in ounces may be estimated in a child as age in years plus 2. It may also be calculated by a more precise formula if needed.5 Infants void 20 times per day, which decreases to about ten times per day by age 3 years.6 The child also learns to resist the urge to void by voluntary contraction of the external sphincter until the detrusor contraction passes and the bladder once again relaxes. Thus, toilet training depends on the development of voluntary detrusor sphincter dyssynergia (DSD), which at times is dysfunctional.7 Finally, full bladder control relies on the child developing volitional control over the spinal micturition reflex to be able to initiate or inhibit detrusor contractions. Most children attain day and night continence by 4 years of age.
Childhood Incontinence
Incontinence is the term used for the unintentional loss of urine after toilet training is achieved. The following definitions are clinically useful:8
Enuresis or nocturnal enuresis: intermittent incontinence while sleeping
Primary nocturnal enuresis: never been continent at night
Secondary nocturnal enuresis: nighttime incontinence following a dry period of at least 6 months.
Daytime incontinence: daytime wetting after toilet training
Stress incontinence: urine leakage due to physically stressful activities such as coughing.
Urge incontinence: unintentional loss of urine when bladder urgency occurs.
The discussion of incontinence is divided into sections on nocturnal enuresis and daytime incontinence, realizing that some children have both. The current recommendation for children with nocturnal enuresis and daytime incontinence is to focus on daytime treatment first followed by nocturnal enuresis therapy.
Nocturnal Enuresis
About 15–20% of children at 5 years of age continue to have bed wetting.9–13 As so many children still wet at night before this age, it is considered within the range of normal and not termed nocturnal enuresis. After age 5, night wetting resolves at the rate of about 15% each year. By age 15 years, it has resolved in 99% of children.13
Etiology
Genetic.
Family history is significant. If both the parents had enuresis, 77% of their offspring will as well. If one parent was affected, 44% of the offspring are affected. If neither parent has a history, only 15% of their children have this problem.12,14
Developmental.
As children grow, bladder capacity increases significantly each year at a proportion greater than urine volume produced.11,15,16 Volitional control over bladder and sphincter also may mature at variable rates and may be related to subtle delays in perceptual abilities or fine motor skills.17
Urodynamic.
Studies show that enuretic episodes occur when the bladder is full, and they simulate normal awake voiding.16 Although nocturnal enuretic patients have more nighttime unstable bladder contractions, these are at low pressure and do not cause leakage.
Sleep Disorders.
Parents of children with nocturnal enuresis are generally convinced that these children sleep deeply and are difficult to arouse. However, this is probably not true. Enuretic patients sleep no more deeply than age-matched controls, wet in all stages of sleep, and show no different awakening patterns. Wetting episodes occur as the bladder fills throughout the night.18
Antidiuretic Hormone.
Antidiuretic hormone (ADH) is released from the pituitary in a circadian rhythm so that levels are higher at night and thus diminish urine output. Some children may undersecrete ADH at night resulting in bed wetting.19–22 Although some patients follow this pattern, others do not; the altered circadian patterns appear to normalize with maturation.23
Treatment
Enuretic Alarms.
Wetting alarms are devices that fit in the underwear of the patients. When moistened, an alarm is sounded. This type of conditioning therapy requires a motivated patient and parents. A variety of products are available with either an audio alarm, a vibrating alarm, or both. In our experience, the best alarm is simply one that is easy to set up and is able to wake the child. The parent may need to help arouse the child, take him or her to the bathroom, and reset the alarm. This may occur multiple times each night, particularly at the onset of therapy. In two studies, wetting alarms were shown to give the best long-term results when compared with other treatments.24,25 The length of treatment to achieve dryness varied between 18 nights and 2.5 months. Relapse may occur in 20–30% of treated children, but re-treatment can be successful.25
Medications.
Imipramine, a tricyclic antidepressant, has been used for many years. The exact mechanism of action is unknown. Initial success has been reported in the 50% range. However, a recent review showed only a 20% success with a relapse rate of 96%.26 Clinical practice reveals that the longer the initial treatment, the more benefit before the effect wanes. It is suggested that the medication be weaned slowly rather than stopped abruptly.
Side effects include anxiety, insomnia, dry mouth, nausea, and personality changes. An overdose can cause fatal cardiac arrhythmias.27 Therefore, medication safety in the home is important. Imipramine may improve response rates to the enuretic alarm.
Desmopressin is an analog of ADH that mimics its urine-concentrating activity without the vasopressor effect.28 The effect is dose dependent, usually requiring 20– 40 µg/day for success.
Complete dryness rates may be highest in patients with a strong family history of success. Efficacy and safety have been demonstrated in a number of studies, but long-term success remains lower than with alarm systems.28–30 Desmopressin may occasionally have side effects, including electrolyte changes, nasal irritation, and headaches. Desmopressin is available as a nasal spray. However, this route is not approved for treating nocturnal enuresis due to a higher incidence of hyponatremia. Parents should be warned to avoid over-hydration to prevent this side effect.
Oxybutynin is the most common drug used for enuresis. It is effective when day and nighttime wetting occur in the same patient, but has no benefit over placebo when nighttime wetting is the only symptom.31
Daytime Incontinence
The patient history is of paramount importance in sorting out the various categories of daytime incontinence.32,33 The physical examination and evaluation should always assess for an abdominal mass or tenderness, distended bladder, normal genitalia, signs of spina bifida occulta, perineal sensation, sacral reflexes, gait, lower extremity reflexes, and urinalysis. Radiographic evaluation, usually voiding cystourethrogram (VCUG) and renal ultrasonography (US), are important in patients with UTI or complex incontinence patterns.
Bladder Instability
Bladder instability is by far the most common diagnosis in children with persistent daytime wetting.34 These children are usually toilet trained, but later develop increasing ‘accidents’ associated with urgency. They describe not knowing that the bladder contraction was coming. They dash to the bathroom or try to ‘hold it in.’ Boys grab and compress the penis, and girls often cross their legs and dance around or squat with the heel compressed over the perineum (Vincent curtsy). In our experience, children with hyperactivity disorders or a willful disposition appear prone to this pattern.
Treatment.
Effective treatment rests on managing all aspects of this condition simultaneously. Constipation is treated with fiber or laxatives, and mineral oil after initial bowel clean-out. Recurring UTIs are managed with prophylactic antibiotics. Bladder instability is treated with timed voiding at frequent intervals (an alarm watch for the child is helpful) and anticholinergics such as oxybutynin or tolterodine.35–37
Biofeedback has gained in popularity for treatment of the VD. Electrodes placed on the perineum near the genitourinary diaphragm can be attached to monitors, an audio signal, or a computer display so the children can learn to relax their external sphincter voluntarily, resulting in better voiding coordination.38–40 The process typically requires four to eight weekly visits, with follow-up as needed.
Neuromodulation has been used mainly in adults who have a refractory overactive bladder; however, there has been recent use in children. Transcutaneous electrical nerve stimulation (TENS) has been popular because of its non-invasive nature, though it requires numerous sessions. The TENS unit is thought to inhibit bladder activity via the pudendal–pelvic nerve reflex. Initial studies show promise with improvements ranging from 73–100% in small series.41,42
Initial success with any treatment is often followed by later relapse. If initial treatment is unsuccessful, it may be successful if re-tried later. Patients older than 8 years who fail treatment should be considered for urodynamic testing. Secondary VUR usually resolves (80%) as bladder function improves.43 The unstable bladder of childhood is usually age limited.
Isolated Frequency Syndrome
A separate, and much less common, group of children present with acute onset of urinary frequency. They appear healthy, are normal on examination, and have normal urinalysis and culture. They do not have true urgency or any wetting, but feel that they must urinate frequently, sometimes every 5 to 10 minutes. They void a very small amount each time. Most sleep through the night and void a large amount on awakening. The pattern may come and go over weeks or months.
Infrequent Voider/Underactive Bladder
On the other end of the voiding spectrum are those children who void only once or twice daily and may not urinate until afternoon after waking in the morning.44 These children have developed urinary retentive behavior without any bladder instability and have dilated, high-capacity, low-pressure bladders.45 Some show an aversion to bathrooms or exhibit excessive neatness, whereas many others appear reasonably adjusted. They may be somewhat prone to UTI and stress incontinence.
Continuous Incontinence
Hinman Syndrome
A small number of children demonstrate persistent incontinence, repeated febrile UTI, VUR, high bladder storage pressures, and very poor emptying.46 This appears to be a deeply ingrained ‘learned’ disorder of severe voluntary DSD. In these patients, the urinary tract has the appearance of a patient with a neurogenic bladder. There is hydronephrosis, a trabeculated bladder, reflux, and sometimes progressive loss of renal function (Fig. 56–1).
FIGURE 56-1 (A) This cystogram shows the typical findings in a patient with Hinman syndrome: trabeculated bladder and severe reflux. (B) This voiding study in the same patient demonstrates dilation of the posterior urethra (asterisk) as a result of chronic contraction of the external sphincter during voiding.
Aggressive therapy with prophylactic antibiotics, anticholinergics, alpha blockers, urodynamic biofeedback training, timed voiding, or clean intermittent catheterization (CIC) may be required.47,48 Some recalcitrant cases may require bladder diversion or augmentation to avoid renal failure. As with many ‘functional’ disorders, the severity of Hinman syndrome tends to wane with maturation, but progressive deterioration may not permit the surgeon to wait.
Neurogenic Bladder
True neurogenic dysfunction of the bladder in childhood results from acquired or congenital lesions that affect bladder innervation. Acquired lesions may occur from trauma to the brain, spinal cord, or pelvic nerves, or as a result of tumor, infection, or vascular lesions affecting these same structures. Congenital lesions include spina bifida and other neural tube defects (most common), degenerative neuromuscular disorders, cerebral palsy, tethered cord, sacral agenesis, and other causes.49
The most practical way to classify neurogenic bladder abnormalities is by a simple functional system: failure to store, failure to empty, or a combination of both.50 Failure to store urine may be caused by the detrusor muscle itself or by the bladder outlet. Detrusor hyperactivity or poor compliance causes elevated bladder pressures and incontinence on this basis. An incompetent bladder neck or urethral sphincter mechanism can be the outlet cause of failure to store urine even if storage pressures are reasonable. Failure to empty can be secondary to the hypotonic, neurogenic bladder which may not generate enough pressure to empty, or increased outlet resistance secondary to striated or smooth muscle sphincter dyssynergia. This classification helps to base treatment on urodynamic data.
Myelomeningocele
The most common cause of neurogenic bladder in childhood are neural tube defects, which range from occult spinal dysraphism to myelomeningocele.51,52 Myelomeningocele is most common, reported in about 1 in 1,000 live births with notable geographic variations.53,54 The etiology is multifactorial, with a clear familial association (2–5% sibling risk) and evidence that periconceptual folic acid supplementation (0.4 mg/day) reduces the risk by 60–80%.55 Improved treatment for the neurosurgical aspects of this lesion since the late 1970s has increased the survival rate. Ninety per cent of newborns with myelomeningocele have normal upper tracts. However, if the bladder is not treated, at least half of these patients show signs of upper tract deterioration or reflux within five years.56 Therefore, early urologic evaluation and continued follow-up is critical in these patients.57,58
Evaluation of the Newborn with Myelomeningocele
Fetal closure of myelomeningocele has been evaluated in a multi-institutional randomized controlled trial.59 The results showed ventriculoperitoneal shunting was reduced by 50% at 12 months of age as was improved psychomotor development and motor function in children who underwent fetal repair. However, fetal intervention was associated with increased maternal and fetal risks. Unfortunately, there is still limited long-term data to demonstrate improved bowel or bladder function for these patients.60
