Disorders of urination are frequently recognised in small animal practice. In particular, urinary incontinence is common in dogs, with a reported prevalence between 5 and 20% in spayed females (Arnold et al, 1989; Forsee et al, 2013). Inappropriate urination is often distressing to owners, especially if their dog is living indoors. Indeed, between 10 and 20% of owners of incontinent dogs reported disharmony within the household, as well as feelings of pity, anger, disappointment or frustration (de Bleser et al, 2011).
In order to treat urinary incontinence effectively, the underlying cause must be identified. This requires a logical and systematic approach. This review focuses on the pathophysiology, investigation and medical management of urinary incontinence in dogs.
Anatomy and physiology of the bladder
The bladder can be divided into the apex (apex vesicae), body (corpus vesicae), and neck (cervix vesicae). The trigone of the bladder (trigonum vesicae) is a triangular area on the dorsal aspect of the bladder neck. The ureters enter at the level of the base of the trigone, and the urethra is located at the apex. The smooth muscle of the bladder is arranged in bundles with different orientations (i.e. spiral, longitudinal and circular). The circular bundle is called the detrusor muscle. The fibres within the detrusor muscle are intimately fused; therefore, stimulation results in complete emptying of the bladder. Smooth muscle bundles extend through the proximal part of the urethra, where they form the internal urethral sphincter (IUS). Further along the urethra, skeletal muscle forms the external urethral sphincter (EUS) (Evans and de Lahunta, 2013).
The control of micturition is attained through a combination of voluntary (i.e. somatic) and involuntary (i.e. autonomic sympathetic and parasympathetic) components of the nervous system (Figure 1). Sympathetic innervation, supplied by the hypogastric nerve, regulates the filling phase. Stimulation of alpha-adrenergic fibres(mainly present in the trigone and proximal urethra) results in contraction of the smooth muscles forming the IUS, while stimulation of beta-adrenergic fibres(mainly present in the body of the bladder) induces relaxation of the bladder. This combined effect facilitates storage of urine and prevents leakage.
As the bladder fills, sensory stretch receptors embedded in the bladder wall are stimulated. Afferent signals are transmitted through the pelvic and hypogastric nerves to the spinal cord, which in turn increase activation of the parasympathetic fibreswithin the pelvic nerve (Nickel and Venker-van Haagen, 1999; Chew et al, 2011). Concurrently, information is relayed to the brainstem and cerebral cortex, allowing conscious perception of bladder distension. Once it is appropriate to void urine, stimulation of the parasympathetic nervous system results in stimulation of the detrusor muscle. Inhibition of somatic efferent neurons in the pudendal nerve, and adrenergic fibres in the hypogastric nerve, result in relaxation of the EUS and IUS, respectively. Additionally, abdominal wall muscle contraction increases intraabdominal pressure and facilitates voiding. If it is not an appropriate time to void, micturition is delayed through the learned ability to maintain the EUS in a contracted state. This is achieved by stimulation of somatic efferent fibresof the pudendal nerve (resulting in contraction of the EUS) and simultaneous inhibition of the somatic efferent fibresinnervating the striated muscles of the abdomen by higher central nervous system centres (Guyton and Hall, 2005; Chew et al, 2011).
Pathophysiology of urinary incontinence
Micturition is the process by which the urinary bladder empties when it becomes filled. Urinary incontinence is a disorder of micturition characterised by the inappropriate leakage of urine, and can be divided into neurogenic and non-neurogenic causes (Figure 2). However, the distinction between these groups is not always clear.
Neurogenic causes of urinary incontinence
Neurogenic causes include lower motor neuron (LMN) and upper motor neuron (UMN) disorders. Lower motor neuron disorders occur secondary to lesions affecting the sacral spinal cord (e.g. sacroiliac luxation, cauda equina syndrome) or the pelvic nerves, which result in the interruption of the local reflex arc in the sacral spinal cord (Chew et al, 2011). This leads to detrusor and sphincter hyporeflexia, characterised by an enlarged bladder that can be easily expressed (Acierno and Labato, 2006).
Upper motor neuron disorders occur when the lesion is located cranial to the sacral spinal cord, such as with intervertebral disc herniation or fibrocartilaginous embolism. This results in the loss of inhibition of the efferent somatic neurons and increased EUS tone. Although bladder detrusor innervation is initially intact, chronic overdistension can lead to decreased bladder tone. Upper motor neuron disorders are characterised by the presence of an enlarged bladder, which is difficult to express. Partial voiding at high bladder volume can be observed because the local reflex arc is intact, which results in urinary incontinence (Chew et al, 2011).
Detrusor-urethral dyssynergia is due to an abnormal contraction of the urethral sphincter during detrusor contraction. Affected dogs initiate voiding normally, but the flow stops abruptly, and is often followed by dribbling of small volumes of urine.
Dysautonomia is a disorder of the autonomous nervous system characterised by mydriasis, third eyelid protrusion or constipation. Additionally, affected animals can have significant voiding dysfunction secondary to bladder atony and/or decreased urethral tone. Urinary incontinence has also been reported in dogs affected with marijuana toxicosis. However, the cause for this remains unclear (Meola et al, 2012)
Non-neurogenic causes of urinary incontinence
Non-neurogenic causes can be divided into anatomical and functional abnormalities. Ureteral ectopia is the most frequent anatomical cause of urinary incontinence (Holt and Moore, 1995). This congenital abnormality is characterised by abnormal entry of one or both ureters caudal to the bladder neck, for example into the urethra or vagina. Dogs with ureteral ectopia will present with continuous or intermittent dribbling of urine, typically from birth (Acierno and Labato, 2006).
Other less common anatomical causes of urinary incontinence include intrapelvic bladder, urovaginal fistula or patent urachus. Both vestibulovaginal stenosis and vestibulovaginal septal remnant, where abnormal tissue is present between the cervix and the vestibule, represent controversial aetiologies for urinary incontinence (Chew et al, 2011; Burdick et al, 2014). In some animals, these conditions represent an incidental finding whereas others may manifest a wide variety of clinical signs, including urinary incontinence, chronic recurrent urinary tract infections, and dysuria (Burdick et al, 2014).
Functional non-neurogenic causes of incontinence include urethral sphincter mechanism incompetence (USMI), detrusor overactivity and overflow incontinence. In the bitch, USMI is the most frequent cause of urinary incontinence (Holt, 1985; Krawiec, 1989) and is characterised by decreased urethral resistance. The pathogenesis of the disease is likely multifactorial. Oestrogen deficiency is thought to contribute; however this is controversial (Noël et al, 2010a). Detrusor overactivity is characterised by increased contractility of the detrusor muscle. This functional cause of urinary incontinence can be further divided into urge incontinence (secondary to infection, tumour or uroliths) and idiopathic instability (without an identifiable underlying cause) (Acierno and Labato, 2006). Overflow incontinence can be secondary to an outflow obstruction or detrusor atony. The associated increase in bladder volume leads to increased intravesicular pressure and urine leakage. Outflow obstruction can be mechanical (e.g. urolithiasis, severe urethritis or stricture) or functional. Functional urethral hypertonicity is the result of increased stimulation of the sympathetic nervous system and can occur secondary to urethral irritation; however in some cases no underlying cause is found (Fischer and Lane, 2007; Noël et al, 2010a). Regardless of the cause, chronic urinary outflow obstruction can result in bladder overdistension and secondary atony by direct damage to the detrusor muscle (Byron, 2015). Detrusor atony can also develop due to electrolyte disturbances or neurogenic causes (Hamaide, 2014).
Diagnosis
Signalment
Common causes of urinary incontinence, together with typical signalment and clinical signs, are summarised in Table 1. Ureteral ectopia is most commonly reported in young female dogs, with constant urinary incontinence reported from birth. Urethral sphincter mechanism incompetence is very rare in sexually intact dogs, but has been reported in up to 20% of spayed females (Arnold et al, 1997). Large breed dogs also appear overrepresented (Grauer, 2002). There have been mixed reports concerning the association between age at neutering and the development of USMI in later life. An increased frequency of incontinence has been described following early ovariohysterectomy in dogs less than 3 months of age (Spain et al, 2004); however, other studies have failed to show an effect (de Bleser 2011; Thrusfield 1998). Urinary incontinence can develop from immediately up to 15 years following ovariohysterectomy; however, it is usually observed within 3 years of surgery (Arnold et al, 1989; Holt, 1985; Nendick and Clark, 1987; Okkens et al, 1997).
| Condition | Typical signalment | Typical clinical signs |
|---|---|---|
| Urethral sphincter mechanism incompetence | Spayed female |
|
| Ectopic ureter | Young female |
|
| Detrusor hyperspasticity | Male or female cats with cystitis |
|
| Detrusor-urethral dyssynergia | Young to middle-aged male |
|
| Urovaginal fistula | Incontinence following spay |
|
| Urorectal fistula | Young male or female, or after trauma |
|
| Neurologic | None | Upper motor: |
History
When a patient is assessed for urinary incontinence, particular attention should be given to the signalment and history. The derived information may allow the clinician to prioritise the differential list in an individual case. Collected information should include:
Polyuria (increased volume of urination) and pollakiuria (increased frequency of urination) should be differentiated from urinary incontinence. Nocturia (urination at night) can be a feature of urinary incontinence. Dogs typically soil the areas in which they sleep because they are unaware of urine leakage. By contrast, micturition in other locations implies at least some control of urination, and is more suggestive of polyuria or pollakiuria. The distinction between polyuria, pollakiuria and urinary incontinence can be difficult, and in some cases more than one of these signs may be present concurrently. Reports of concurrent faecal incontinence or other neurological abnormality suggests a neurological cause.
Polyuria is not a feature of uncomplicated urinary incontinence. However, polydipsia and polyuria can lead to an increased volume of urine within the bladder, increased intravesicular pressures, and clinical signs of urinary incontinence in animals with otherwise subclinical disease. In addition, affected animals are predisposed to bacterial urinary tract infections, and the development of secondary pyelonephritis can be associated with polyuria in some cases.
Physical examination
Complete physical and neurological examinations should be performed. Physical examination should include a detailed examination of the perineal or preputial area to identify urine staining or evidence of secondary pyoderma. Urination should be observed to evaluate the ability to initiate urination, the presence or absence of stranguria or urinary tenesmus, and the diameter of the urine stream. The urinary bladder should be palpated before and after voiding to evaluate its distension, size and tone. Manual bladder expression provides information regarding sphincter tone and may help differentiate between UMN and LMN disorders if a neurogenic condition is suspected. Digital vaginal examination should be performed in female dogs to evaluate the presence of a mass within the genitalia or distal urethra.
A rectal examination is performed to evaluate anal tone and to assess the prostate gland, urethra and pelvic diaphragm. Decreased anal tone can be observed in animals with LMN incontinence because the sacral segment of the spinal cord and the pudendal nerve also innervate the anal sphincter. The perineal and bulbocavernosus reflexes can also be assessed (Grauer, 2002; Lorenz et al, 2011). In all cases, an orthopaedic examination should also be performed. Degenerative joint disease is common in older animals and may contribute to difficulty urinating.
Diagnostic investigation
Clinical pathology
The minimum database should include a complete blood count, biochemistry profile, urinalysis (Table 2), and urine culture to identify concurrent disorders that could worsen clinical signs (e.g. a disease causing polyuria or polydipsia). Additionally, urinary tract infection can be a cause (e.g. urge incontinence) or consequence of urinary incontinence. Therefore, it is important to exclude urinary tract infection in any animal presented for urinary incontinence (Grauer, 2002; Acierno and Labato, 2006; Lorenz et al, 2011).
| Urine colour | Cause |
|---|---|
| Dark yellow | Concentrated urine |
| Pale yellow | Normal |
| Yellow-orange | Bilirubin, fluorescein, concentrated urine |
| Green-blue | Biliverdin, methylene blue |
| Brown-black | Bile pigments, myoglobin, methaemoglobin |
| Yellow-brown | Bile pigments |
| Red | Haemoglobin, red blood cells, myoglobin, dyes |
| Milky | Pyuria, lipiduria, phosphate crystals |
| Colourless | Dilute |
| Agent | Recommended dosage | Possibe adverse effects | Caution |
|---|---|---|---|
| Phenylpropanolamine | 1–1.5 mg/kg q8h to q12h, PO 1.5 mg/kg q24h, PO | Restlessness, hypertension, anorexia, tachycardia, anxiety, increased intraocular pressure, hepatic glycogenolysis, irritability, aggression | Cardiovascular disease, prostatic hypertrophy, hypertension, hyperthyroidism, glaucoma, diabetes mellitus |
| Ephedrine | 1–4 mg/kg q8h to q12h, PO | Restlessness, hypertension, tachycardia, anxiety, excitability | Cardiovascular disease, prostatic hypertrophy, hypertension, hyperthyroidism, glaucoma, diabetes mellitus |
| Pseudoephedrine | 0.2-0.4 mg/kg q8h to q12h, PO | Restlessness, hypertension, tachycardia, anxiety, excitability | Cardiovascular disease, prostatic hypertrophy, hypertension, hyperthyroidism, glaucoma, diabetes mellitus |
| Oestriol | 0.5–2 mg per dog q24h, PO | Vulvar swelling, attraction of males, metrorrhagia, pyometra, bone marrow toxicity | Pregnancy (abortifacient, teratogen) |
| Deslorelin | Dog < 30 kg 4.7 mg implant |
Local swelling, pain | No labeled contraindications |
Urine sample processing
Urine should preferably be examined within 30 minutes. If this is not possible, it should be refrigerated at 4°C and analysed when at room temperature. Urine analysis consists of four components: colour and turbidity; chemical analysis using semiquantitative, colorimetric reagent strips; measurement of specific gravity; microscopic analysis of the sediment (casts, cellular components, and crystalluria). To examine the sediment, 3 to 5 ml of urine should be centrifuged at 2000 rpm for 5 minutes. Next, most of the supernatant should be discarded, leaving approximately 0.5 ml in the tube. The remaining supernatant is then resuspended and a drop is transfered to a microscope slide. Last, to assess the sample a coverslip should be placed.
Diagnostic imaging
Abdominal ultrasonography and radiography are performed to identify structural conditions affecting the bladder, urethra, pelvis, or spine. Ultrasonography is mainly used to evaluate the size of the bladder and its wall integrity, detect the presence of masses or uroliths, examine the prostate and identify the size and terminal openings of the ureters (Lorenz et al, 2011). Survey abdominal radiographs are primarily used to assess the size and position of the bladder and vesicourethral junction, and to identify radioopaque uroliths.
Contrast radiographic techniques include retrograde vaginourethrography, urethrocystography or excretory urography. Such studies can identify ectopic ureters, with a reported sensitivity between 70% and 78.2% (Cannizzo, 2003; Samii et al, 2004). The use of computed tomography excretory urography increases sensitivity to 91% (Cannizzo, 2003; Samii et al, 2004). Positive and negative retrograde contrast techniques may also be used to identify intravesicular masses and uroliths; however, ultrasonography offers a more sensitive and less invasive alternative.
Retrograde contrast techniques are not without risk (Kealy and McAllister, 2005). Overdistension of the bladder can result in rupture, which may be more likely in animals with preexisting bladder disease. In addition, negative contrast cystography (pneumocystography) can result in fatal air embolism. For this reason, it is recommended to place the dog in left lateral recumbency during the procedure to facilitate retention of air within the right atrium. If air embolism occurs, the dog should remain in left lateral recumbency with the head lower than the body for at least 60 minutes. It has been suggested that the use of carbon dioxide or nitrous oxide rather than air may decrease the likelihood of air embolisation. In addition, air should not be used in the presence of haematuria or recent trauma. Some clinicians prefer to avoid pneumocystography due to the associated risks.
Endoscopy
Direct identification of ectopic ureters by cystoscopy is the gold standard for diagnosis of ureteral ectopia (Cannizzo, 2003; Samii, 2004). Although sensitivity of up to 100% has been reported, this is dependent on the skill of the examiner (Adin, 2004). Endoscopy also allows assessment of the urogenital tract for other structural abnormalities, and can be used to facilitate mucosal biopsy or urolith acquisition for analysis.
Patient preparation
The perivulvar region is clipped and scrubbed to reduce contamination. Following this, an antiseptic vaginal flush (0.05% chlorhexidine acetate solution) should be used before cystoscopy. Last, a sterile fenestrated drape to expose the vulva is placed over the patient (Morgan and Forman, 2015).
Urodynamic studies
Urodynamic studies are used to evaluate the pressure-flow relationship between the bladder and the urethra, which represents the functional status of the lower urinary tract (Goldstein and Westropp, 2005).
The urethral pressure profile (UPP) is used to assess urethral tone. The indications of UPP include suspected primary USMI, idiopathic urethral hypertonicity and detrusor urethral dyssinergia. Cystometrography allows recording of the relationship between bladder pressure and bladder volume. This technique is used to assess detrusor abnormalities such as detrusor overreactivity or detrusor atony. Although urodynamic studies are the only method of confirming USMI, they are not widely available.
Treatment
Medical management
The management of urinary incontinence is dependent on the underlying disease process. When possible underlying causes should be addressed. For example, ureteral ectopia will require surgical correction, urinary tract infections should be treated with appropriate antibiotic therapy, and urolithiasis may require a combined surgical and medical approach. The following section will concentrate on the management of USMI in females.
USMI in females
Phenylpropanolamine is a non-selective α-adrenergic agonist that increases IUS tone (Ek, 1978; Acierno and Labato, 2006). Phenylpropanolamine is efficacious in up to 90% of cases (Richter and Ling, 1985; White and Pomeroy, 1989). Unfortunately, patients treated for a prolonged period of time are more likely to develop drug resistance and recurrence of clinical signs (White and Pomeroy, 1989). The main adverse effects include hypertension, increased intraocular pressure, hepatic glycogenolysis, restlessness, anxiety and tachycardia (Krawiec, 1988; Webster, 2001; Carofiglio et al, 2006; Noël et al, 2010b). Therefore, it should be used judiciously in patients with concurrent cardiovascular disease, hypertension, glaucoma, and diabetes. Aggression has also been reported in some dogs.
Ephedrine is a mixed-acting sympathomimetic drug that increases urethral function and improves bladder storage function (Noël et al, 2012). A complete response to ephedrine has been reported in 74% of females with USMI (Arnold et al, 1989). Side effects of ephedrine include restlessness, hypertension, excitability and tachycardia (Krawiec, 1988; Carofiglio et al, 2006). Pseudoephedrine, a stereoisomer of ephedrine, has shown less efficacy and more side effects when compared with phenylpropanolamine for the treatment of USMI (Byron et al, 2007).
The urethra possesses high-affinity oestradiol receptors, and oestrogens are known to increase the number and sensitivity of α-adrenergic receptors (Larsson et al, 1984). Oestriol is a short-acting natural oestrogen with few side effects (Clark and Markaverich, 1984). In one study, complete continence was achieved in 65% of females treated with oestriol (Mandigers and Nell, 2001). Reported side effects were minor, and included swelling of the vulva, attractiveness to males and a haemorrhagic vulval discharge (Mandigers and Nell, 2001). Although apparently rare, pyometra and bone marrow suppression have been reported with long-term use (Hendriks and Janszen, 1998). Oestradiol or diethylstilboestrol are long-acting synthetic oestrogen preparations that are more commonly associated with bone marrow supression (Osborne et al, 1980; Krawiec, 1989).
In theory, the administration of oestriol prior to phenylpropanolamine could increase the number of urethral α-adrenergic receptors, thereby increasing the potential effect of phenylpropanolamine. In one small study in healthy dogs, the combined administration of phenylpropanolamine and oestriol did not increase the urethral resistance more than oestriol alone (Hamaide et al, 2006). However, anecdotally the combined administration of both drugs concurrently may be effective in some clinical cases that fail to respond to either drug alone.
Gonadotropin-releasing hormone (GnRH) analogues (e.g. deslorelin) are less efficacious compared with phenylpropanolamine for the treatment of USMI (Reichler et al, 2006). However, because of the few side effects reported with these medications, they could be considered as an alternative treatment option when phenylpropanolamine is contraindicated.
There are a variety of surgical options for the treatment of USMI in female dogs. Colposuspension involves the surgical advancement of the bladder neck from an intrapelvic to an intraabdominal position by attachment of the vagina to the prepubic tendon (Holt, 1985; White, 2001). Following colposuspension, continence has been reported in 42–56% of cases with surgery alone, with improvement in the severity of signs in an additional 40–42% of cases (Holt et al, 1990; Marchevsky, 1999). However, long-term follow up has revealed continence rates of only 14% 1 year after surgery (Rawlings, 2001). In such cases, combined medical and surgical management may be effective. Additional surgical treatments include cystourethropexy, urethropexy urethral sling, transobturator vaginal tape, urethral lengthening and sphincter reconstruction techniques.
Endoscopic periurethral injection of Teflon or glutaraldehyde cross-linked collagen can increase continence in females with USMI. This technique involves submucosal injection, which results in mucosal bulging and partial obstruction of the urethral lumen and improved closure pressures. Although 68% of dogs achieve continence following the procedure, and an additional 25% demonstrate improvement of clinical signs, urethral incontinence can recur (Arnold et al, 1989; Arnold, 1996; Barth, 2005). Repeat injection with or without the addition of medical therapy is possible in cases with recurrence of signs.
Artificial sphincter implantation has been described (Adin, 2004; Hill et al, 2014). In the largest case series, a silicone hydraulic occluder was placed around the proximal urethra and connected to a subcutaeous infusion port which could be inflated or deflated to improve continence or allow urination, respectively (Currao, 2013). Static inflation could also be used to improve urethral pressure while allowing voluntary urination. Functional continence was achieved in 12 of 18 dogs; although higher success was observed in dogs with owners that were compliant with inflations (Currao, 2013).
USMI in males
Urethral sphincter mechanism is reported less frequently in male dogs. Treatment with alpha-adrenergic agonists and oestriol may be effective in some cases, but appears less successful in comparison to females (Aaron, 1996). Cranial advancement of the bladder can be achieved by pexy of the vas deferens, using either conventional surgery or laparoscopy (Weber, 1997; Salomon, 2002). Urethral teflon injections and prostatopexy have also been reported (Holt, 2005).
Other acquired disorders
Urinary incontinence associated with spinal disease, urinary tract infection, urolithiasis or neoplasia, should be addressed by managing the underlying disease process.
Idiopathic detrusor instability is treated with anticholinergic drugs in dogs. Oxybutinin is the treatment of choice for this rare condition (Lappin and Barsanti, 1987; Lane, 2001). Other drugs reported for treatment of detrusor idiopathic instability in dogs include propantheline (Labato, 1988; Lane, 2001) and emepronium bromide (Holt, 1984).
Conversely, the cholinergic agonist bethanechol is used for treatment of detrusor atony. Bladder contraction is induced by stimulation of muscarinic receptors (Noël et al, 2010c). The clinical efficacy of bethanechol is however questionable. Other drugs used in case of secondary bladder atony include alpha blockers (e.g. prazosin) and somatic muscle relaxants (e.g. diazepam).
Functional urethral hypertonicity (idiopathic urethral hypertonicity or detrusor urethral dyssynergia) can be treated either by a non-selective, non-competitive α-antagonist (phenoxybenzamine) or by a selective α1-antagonist (prazosin). As increased tone of the urethral striated musculature can also occur in detrusor-urethral dyssynergia, somatic muscle relaxants such as diazepam or dantrolene can be considered (Noël et al, 2010a).
Regardless of the underlying cause of urinary incontinence, it is also important to attempt to prevent complications such as urine scald and secondary pyoderma. Frequent bathing of urine soaked areas should be performed. In addition, the application of a barrier cream may decrease the likelihood of urine scald, and secondary infections should be treated with appropriate antimicrobial therapy.
Conclusion
Urinary incontinence is a presenting complaint that needs a thorough and systematic history taking, physical examination, observation of the animal and diagnostic work-up in order to identify the ongoing disease and select a targeted treatment. Several medical treatment options are available although surgery is indicated in some cases.