The pathophysiology of urinary incontinence: part 2

Urinary incontinence (UI) is a common problem affecting up to two thirds of all women. Its prevalence is easily underestimated in the clinical setting, since patients will often fail to bring the condition to the attention of their physician. It is estimated that only one in four symptomatic women seek help for this problem.¹

Common types of UI in females are:² urge incontinence, stress incontinence and mixed incontinence. In addition there are other types which are not typical of stress or urge incontinence. They are, transient incontinence, overflow incontinence,  unconscious (unaware) incontinence, continuous incontinence, extra-urethral incontinence, nocturnal enuresis and post micturition dribble.

Urge incontinence

This is the most common type of UI in older persons. It is characterised by abrupt urgency, frequency and nocturia. The volume of leakage may be small or large. The term overactive bladder (OAB) refers to a condition with frequency, nocturia and urgency or urge incontinence or both. Urge incontinence is associated with detrusor overactivity.

• Part one of this article is available here

Since detrusor overactivity is found in healthy continent older persons, failure of lower urinary tract and functional compensatory mechanisms may play an important role in UI. Distinction between detrusor hyper-reflexia and instability are frequently blurred in older persons. Less common causes of urge UI are interstitial cystitis and spinal cord injury that results in impaired detrusor compliance causing excessive pressure response to filling or detrusor -sphincter dyssynergia causing detrusor and sphincter concomitant contraction or both.

Detrusor overactivity may coexist with impaired detrusor contractility, which is termed as Detrusor Hyperactivity with Impaired Contractility (DHIC) with an elevated post void residual volume in the absence of outlet obstruction. This accounts for most established UI in frail and older persons. Women can be misdiagnosed with stress incontinence if weak DHIC contractions are not detected and they may be at increased risk of urinary retention if treated with bladder relaxant drugs.

Urethral instability

The diagnosis of urethral instability occasionally is made following the urodynamic workup of incontinence when a fall in urethral pressure is observed with a stable bladder pressure and coincident urinary leakage. Some believe that urethral instability represents a variant of detrusor instability where pressure equalisation occurs rapidly between the bladder and urethra, therefore the rise in intravesical pressure indicative of detrusor instability is not observed. Others found that conventional pharmacotherapy for detrusor instability does not improve urethral instability and this finding suggests that the pathophysiology of urethral instability may be different.

Stress incontinence

Stress incontinence, the second most common type of UI in older women, results from failure of the sphincter mechanisms to preserve outlet closure during bladder filling. Stress incontinence occurs coincident with increased intra abdominal pressure, in the absence of a bladder contraction. The basic pathology is urethral incompetence. This can be due to the following:

Urethral hyper-mobility

It occurs in 80-90% of patients3 and this results from loss of the normal pelvic support mechanism of the bladder and urethra due to trauma and stretching during vaginal delivery, hysterectomy, hormonal changes associated with menopause,  pelvic denervation and congenital weakness. If the loss of urethral support is thought to be the primary pathology for incontinence, then the disorder is known as genuine stress incontinence (GSI).

Intrinsic sphincter deficiency (ISD)

This occurs with trauma and scarring from multiple prior operations, anti-incontinence surgery, radiation, neurogenic disorders such as diabetes mellitus or with severe urethral atrophy. Unlike the episodic leakage of GSI, this leakage is typically continual and can occur while the person is sitting or standing quietly.

During time of increased intra abdominal pressure, individuals with stress incontinence may display hypermobility or rotational descent of the urethro-vesical junction. Damage to nerves, muscle and connective tissue of the pelvic floor is important in GSI.

During intrapartum period three types of lesions can occur. These are levator ani muscle tears, connective tissue breaks and pudental/pelvic nerve denervation.The long-term result may be the loss of active and passive urethral support and loss of intrinsic urethral tone. Under normal circumstances, any increase in intra abdominal pressure is transmitted equally to the bladder and proximal urethra. This is likely due to the retropubic location of the proximal and mid urethra within the sphere of the intra abdominal pressure. At rest the urethra has a higher intrinsic pressure than the bladder. When the urethra is hypermobile as it descends and rotates under the pubic bone and pressure transmission to the walls of the urethra may be diminished. Intra urethral pressure can fall below bladder pressure resulting in urine loss.

Potential incontinence

Potential or masked incontinence refers to stress incontinence that is revealed only after a reduction of severe pelvic organ prolapse. In these individuals, kinking of the urethra caused by the prolapse itself provides for at least part of the continence mechanism. In some patients, a history of stress incontinence with improvement and finally resolution of their symptoms coinciding with worsening of their prolapse can be recounted.

In the diagnosis of potential incontinence, the goal is to avoid new onset incontinence following surgical correction of their prolapse. In such patients procedures such as colposuspension or sling should be considered. Diagnosis can be made by stress testing with the prolapse reduced or by pessary placement and pad testing. No particular method of prolapse reduction has been shown to be superior.

Overflow incontinence

This is related most commonly to bladder neuropathy. Diabetes mellitus is a common aetiology of the neurogenic bladder. Lumbosacral nerve disease from tumours, meningomyelocoele, multiple sclerosis and prolapsed intervertebral discs also can result in bladder neuropathy and overflow incontinence. High spinal cord injuries are another aetiology. Severe cases of outflow obstruction can cause severe retention, local neurological injury and overflow. In most cases sensory and motor neuropathy are present. The maximal physical capacity of the bladder is reached many times without the individual realising that this has occurred. Effective emptying is not possible because of an acontractile detrusor muscle.

Continuous incontinence

This severe type of incontinence is characterised by constant or near constant leakage with no symptoms other than wetness. Generally this represents some significant breach in the storage capabilities of the bladder or urethra. Urogenital fistulas are a classic example. Other causes are congenital malformations of the genito-urinary tracts, ectopic ureters etc. A non functioning urethra also can result in continuous leakage. It can result from scarring and fibrosis due to surgery, radiation injury, lower motor neuron disease etc.

Transient incontinence/functional incontinence

UI precipitated by correctable factors are called transient incontinence or functional incontinence. It is due to the inability to hold urine due to reasons other than neuro-urological and lower urinary tract dysfunction.

It affects approximately one third of community dwelling older persons and accounts for one half of the incontinence among hospitalised older persons. The common causes are urinary infections, medications, restricted mobility, delirium, confusional state, faecal impaction, psychiatric disorders etc. In some cases, the cause is of a transient nature and in other instances a permanent problem can be identified. The aetiology of the incontinence may be iatrogenic, environmental situational or disease related.

A commonly quoted mnemonic is helpful in remembering the functional contributors to incontinence is: D I A P P E R S (Delirium, Infection, Atrophic changes, Pharmacological agents, Psychiatric illness, Endocrine disorders, Reduced mobility, Stool impaction).⁴

Clinical management

The multi-factorial nature of UI in older persons requires a comprehensive diagnostic evaluation with a careful search for all possible causes and precipitants beyond a focus on specific genito-urinary diagnosis. The evaluation must determine the cause of the incontinence and exclude serious conditions. Good understanding of the pathophysiology of the different types of incontinence and identifying the precipitating factors by systematic evaluation is the key point for the effective treatment.

The following incontinence specific quality of life scales are recommended when therapies are being evaluated: ICIQ, BFLUTS, I-QOL, SUIQQ, UISS, SEAPI-QMM and KHQ.⁵

History Careful history taking by symptoms assessment may help to determine the type of incontinence such as urgency symptoms, immediate leak after coughing or sneezing, leaking after few seconds or post micturition, dribbling, continuous leak or leak during physical activity etc. Other urological symptoms such as straining, feeling of incomplete emptying and poor flow and associated symptoms such as dysuria, haematuria, suprapubic pain, perineal pain etc will give help to identify the problem.

Obstetric and gynaecology history such as menstruation, HRT, past pregnancies and child births, irradiation, pelvic/perineal surgeries etc and other diseases such as diabetes, neurological illness, cancer, constipation, cardiac, renal diseases, medications such as alpha blockers, sedatives, anticholinergics, diuretics are essential in evaluation. Personal history such as alcohol intake, caffeine, tobacco, alteration in bowel habit/sexual function will also help in management decisions.

Voiding record

The optimum duration of record depends on the clinical context: 24 hours is a reasonable duration. However, a three day recording is recommended for accurate assessment.

• Frequency volume chart€”this records the volume voided as well at the time of each micturition, day and night for at least 24 hours
• Bladder diary€”this records the time of micturition and voided volumes, incontinence episodes, pad usage and other information such as fluid intake, the degree of urgency and the degree of incontinence.
• The following measurements can be deducted from these: day time frequency, night time frequency, polyuria, nocturnal polyuria, average volume voided, incontinence episode frequency, urgency and pad usage.

Physical examination

General examination: Height and weight and body mass index.

Abdominal examination: Palpable bladder, mass, scars of previous surgeries.

Neurological examination: Mainly higher functions and sacral segments. Mini mental scores in elderly, lower limb movements, hand dexterity etc.

Perineal examination: Perineal sensations, skin excoriations, stress test, assessment of urogenital fistulas, assessment of bladder neck mobility and the presence of pelvic organ prolapse, especially on straining, vaginal examination to assess the pelvic floor muscle function and rectal examination to assess the anal tone, consistency of stool, and also to assess the pelvic floor muscle.

Baseline tests

Urine analysis – reagent strip test for microscopic haematuria, infection, diabetes and urine for culture or cytology as indicated

Blood- biochemical tests for renal function for everyone and blood glucose and calcium for those who have polyuria

Post void residual volume -assessed by ultrasound scan or catherisation

Other tests -pad test/short test (one hour) or 24 hour test-although not highly recommended by the International Continence Society, it is considered as an option for the routine evaluation of UI. It quantifies urine loss based on the measurement of weight gain of absorbent pads during a test period under standardised conditions. A weight gain of greater than 1g is considered as positive in one hour test and 4g is considered as positive for 24 hour test.

Uroflometry

It measures flow rate, maximum flow rate, average flow rate, voiding time, flow time and voided volume. It should be considered as a screening test for voiding difficulties in all women with symptoms of lower urinary tract dysfunction. It is essential prior to surgery for stress incontinence as some women have occult voiding dysfunction unrecognised by the patient and difficulty in voiding may increase after surgery and can lead to retention.

Cystometry (filling and voiding)

The pressure in the bladder and rectum is measured during bladder filling. Intra abdominal pressure is subtracted from bladder pressure to give a real indication of detrusor pressure. It measures vesical pressure, abdominal pressure, filling volume, urine flow rate, bladder sensation (first/strong desire to void) and bladder pressure. This test should be carried out if neuropathy or voiding difficulty is suspected or if invasive treatment is considered or to exclude detrusor overactivity/underactivity or if the history and clinical examination do not lead to a definite diagnosis. In stress incontinence cystometry confirms the diagnosis when urine leakage occurs during an increased intra abdominal pressure in the absence of detrusor contraction.

Electro-myography

Electro-myography of the urethra is predominantly used in patients with neuropathic disorders or in research studies. It studies the electrical potentials of the urethral sphincter using needle or skin electrodes and ideally it is performed during cystometry. Electromyography of the perineal muscles is proposed in overactive bladder when a neuropathy is suspected.

Imaging

Upper tract imaging

Ultrasound scan is the least invasive test and it is indicated in all cases of neurogenic incontinence and chronic retention. Upper tract imaging is also indicated if extra urethral UI and congenital disorders is suspected. Ultrasound has a role in detecting the residual urine as well. Lower urinary tract imaging such as video-urodynamics or voiding cystourethrography may be a reasonable option in the preoperative evaluation of complicated or recurrent UI and is not indicated routinely in primary uncomplicated UI.

Direct visualisation

Cystoscopy can evaluate the urethral closing mechanism. It can be considered in urge incontinence to exclude other pathologies especially in the case of microscopic haematuria, in recurrent and iatrogenic case prior to surgery, and when fistula is suspected.

Treatment

Treatment can be sub divided into three categories: primary level management, specialised management and management of symptoms in frail and elderly women.

Initial assessment

This should identify the complicated incontinence group, which will include urinary fistulas, women with special needs, and those with pain, haematuria, recurrent infections, significant pelvic organ prolapse, recurrence after previous surgeries, and in those who had radical pelvic surgeries etc who will need specialised management. The uncomplicated incontinence group will include the three main groups such as stress incontinence, urge incontinence and mixed incontinence. They are further managed as mentioned below.

Treatment

Primary level treatment includes lifestyle interventions such as weight reduction, smoking cessation and fluid/dietary modification (including caffeine) and medications. It also include supervised pelvic floor muscle training, supervised bladder training, treatment for oestrogen deficiency and UTI if found.

In mixed incontinence the predominant symptom is addressed first and in some women the significant pelvic organ prolapse can be treated with ring pessary with the concurrent use of incontinence products while waiting. Initial treatment should be maintained for 8-12 weeks and in some women significant pelvic organ prolapse can be treated with vaginal devises that treat both incontinence and prolapse.

Antimuscarinics

Antimuscarinics are still the most widely used medication in the treatment of urgency and urge incontinence due to detrusor overactivity (OAB). They act by blocking the muscarinic receptors on the detrusor muscle that are stimulated by acetylcholine released by activated parasympathetic nerves thereby reducing the ability of the bladder to contract.

They act mainly during the storage phase during which the baseline secretion of acetylcholine is minimal and antimuscarinics can compete efficiently with acetylcholine for the muscarinic receptors. During micturition phase, large amounts of acetylcholine is released due to the intense parasympathetic activity and the action of antimuscarinics is overwhelmed. These include oxybutinin, (oral/transdermal patch) tolterodine, solifenacin, trospium chloride, darifenacin, fesoterodine and propiverine. Their side effects include dry mouth, blurred vision, changes in mental state, nausea and constipation. They are contraindicated in closed angle glaucoma and myasthenia gravis.

Desmopression

Desmopression is a synthetic vasopressin analogue with a profound antidiuretic effect, which is achieved by increasing the osmotic reabsorption of solute free water through the cells of the collecting ducts resulting in the excretion of a much smaller volume of concentrated urine. It is mainly used for primary nocturnal enuresis.

Duloxetine

Duloxetine is a combined norepinephrine and serotonin reuptake inhibitor that increases the sphincteric muscle activity during filling phase of micturition. By inhibiting the reuptake of noradrenaline and serotonin, it increases the contractile activity in the striated sphincter nicotinic receptors. Duloxetine allows complete relaxation of the sphincter for efficient voiding during micturition when the action of glutamate ceases. It is therefore used in stress UI.

Botulinum toxin

There are seven types of this but only types A&B are used clinically in urology. The toxin blocks the release of acetylcholine and other neurotransmitters from presynaptic nerve endings at the myoneural junction. This results in decreased muscle contractility and muscle atrophy at the injection site. The chemical denervation produces an irreversible process and cure with regeneration of the new nerve terminals in about three to six months. A good response is obtained within one week and lasts from six to nine months before reinjection is necessary. It does not cross the blood brain barrier and hence has no CNS effects. It is injected directly into detrusor muscle or suburothelially via a cystoscope under local or general anaesthesia.

Mirabegron

Mirabegron is from a class of drugs called beta 3 agonists. It works by stimulating certain receptors in the detrusor muscle of the bladder wall. Mirabegron is recommended by NICE as an option for treating the symptoms of overactive bladder only for people in whom antimuscarinic drugs are contraindicated or clinically ineffective, or have unacceptable side effects.⁶

Assessment

A complicated incontinence group of patients will need additional evaluation and tests such as imaging and cystoscopy, urinary cytology etc, and those patients who are known to have fistula secondary to childbirth injury, should be managed in specialist fistula units.

For an uncomplicated group who failed the initial management or for those whom the quality of life is impaired, an interventional therapy is desirable. Prior to intervention urodynamic testing is highly recommended to identify the exact type and to make a definite management plan. Systematic assessment of the pelvic organ prolapse is highly recommended and it should be treated appropriately.

Treatment of urinary incontinence

Urge incontinence secondary to idiopathic detrusor overactivity that fail medical management may be treated by neuromodulation or bladder augmentation. Other options are detrusor myomectomy and Botulinum toxin injection. If urodynamic stress incontinence is confirmed, then the treatment options that are recommended for patients with some degree of bladder neck and urethral mobility include the full range of non surgical treatments as well as retropubic suspension procedures and bladder neck/sub urethral sling operations. The correction of symptomatic pelvic organ prolapse may be desirable at the same time. Those patients with voiding dysfunction leading to significant post void residual urine (>30% of total bladder capacity) may have bladder outlet obstruction or detrusor underactivity and may need intermittent self catheterisation.

Surgical procedures

Surgery for stress incontinence include intra urethral injection therapy, cysto urethropexies such as Burch retropubic suspension, low tension vaginal tape procedures, classical sling procedures, and artificial sphincter surgery. Surgery for UI include augmentation cystoplasty, autoaugmentation and sacral nerve stimulation.

Management in frail and elderly women

Older persons in general should receive a similar range of treatment options as younger patients, however frail older persons present different problems and challenges compared with other fitter older patient populations. The term ‘frail’ include such patients who neither wish nor are fit enough to be considered for the full range of therapies likely to be offered to healthier or younger persons. The extent of investigation and management in frail older people should take into account the degree of bother to the patient and/or to the carer, their motivation and level of co-operation/compliance as well as the overall prognosis and life expectancy. At the same time management effective to meet their goals is possible for many frail patients.

Assessment

History and clinical assessment should identify treatable or potentially reversible conditions causing incontinence such as infections, drug induced, delirium, stool impaction, diuretic therapy etc. Post void residual urine measurement is recommended as it may influence the choice of treatment.

Initial management

Intial treatment should be individualised and influenced by most likely clinical diagnosis. Lifestyle changes, bladder training in more fit and alert patients and assisted and prompted voiding for more frail and cognitively impaired patients can be attempted. Judicious usage of medications such as antimuscarinics for urge incontinence and alpha blockers to assist bladder emptying in those with high residual urine may be tried. These medications should be used with caution and should be started with a low dose.

Specialised management

Age is not a contraindication for incontinence surgery but all comorbidities should be addressed and adequate trial of conservative therapy should be attempted prior to consideration of surgery and an urodynamic study should be carried out as clinical diagnosis may be inaccurate. Ongoing management and reassessment should aim to achieve either independent continence (dry, not dependant on ongoing treatment) or dependant continence (dry with assistance, behavioural treatment and or medications) or contained incontinence (incontinence contained with use of appropriate aids or appliances). Importantly, optimal care can usually be achieved by combination of the above approaches.

Conclusion

UI is common in women but it is under reported and undertreated. Generally UI is caused by ageing, childbirth, pelvic surgery and neurological disorders. Most UI can be evaluated and treated in the primary care setting after careful history and simple clinical assessment. This can include lifestyle modifications, pelvic floor muscle training, bladder training and pharmacotherapy. If there is complex symptomatology or if the primary management fails, then referral to a specialist is suggested.

UI can be very distressing both physically and psychologically and impacts on quality of life and health. GPs as primary care providers, should evaluate, treat and refer high risk patients. The treating clinicians should make use of the guidelines such as EAU guidelines and NICE guidelines in the management of these patients in a cost effective and safer way.

Part one of this article is available here

Conflict of interest: none declared

References

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5.Perry S, Shaw C, Assassa P, et al. An epidemiological study to establish the prevalence of urinary symptoms and felt need in the community: The Leicestershire MRC incontinence study. Journal of Public Health Medicine 2000; 22: 427-34

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