URINARY INCONTINENCE IN DOGS AND CATS

Urinary incontinence is a disorder of micturition characterized by involuntary escape of urine during the storage phase of urinary cycle. The most common presentation is intermittent or continuous dribbling of urine combined with episodes of normal voiding.

Pathophysiology

Micturition depends on the coordinated actions among the sympathetic, parasympathetic, and somatic nervous systems and central control centers. The coordination between these systems takes place in the pontine micturition center (PMC), also known as Barrington’s nucleus, which is located in the dorsomedial pontine tegmentum in the brainstem. The PMC receives input from other sensory stimuli to determine the onset of micturition.

The urinary cycle is divided into two phases: the filling phase, and the emptying phase. The sympathetic innervation, supplied by the hypogastric nerve, regulates the filling phase. The Sympathetic preganglionic fibers exit the lumbar spinal cord (L1-L4 in dogs and L2-L5 in cats) and synapse in the caudal mesenteric ganglia. Postganglionic fibers (hypogastric nerve) release norepinephrine (NE) to activate β-receptors in the body of the bladder, resulting in relaxation and stretching, while stimulation of α-receptors in the trigone region and proximal urethra causes constriction. In addition, the sympathetic stimulation inhibits urination by blocking parasympathetic transmission.

As the bladder fills, sensory receptors embedded in the bladder wall become activated. Information from these receptors travels via the pelvic nerve to the spinal cord, where the information is relayed to the PMC of the brain stem. The PMC determines the onset of micturition.

The Parasympathetic preganglionic motor neurons arise from the sacral spinal cord segments S1 to S3. Preganglionic fibers travel in the pelvic nerve and synapse in the peripheral ganglia in the wall of the bladder. Short postganglionic fibers provide excitatory input to the bladder through ACh acting on cholinergic (muscarinic) receptors in the bladder and also provide inhibitory input to the urethra, thus facilitating voiding. The pudendal nerve is simultaneously inhibited, allowing relaxation of the external urethral sphincter.

Somatic innervation, supplied via the pudendal nerve, also arises from the sacral spinal cord segments S1 to S3 and provides stimulation (via ACh on nicotinic receptors) to the external urethral sphincter, an area of striated muscle. Cell bodies of this nerve are located in the ventrolateral nucleus of Onuf.

Urinary incontinence (UI) refers to unconscious voiding of urine, whereas consciously voiding small amounts of urine in inappropriate locations (pollakiuria is referred to as urge incontinence.

Conditions causing incontinence

1.      Urethral Sphincter Mechanism Incompetence (USMI)

USMI usually occurs in spayed female dogs, but can occur in intact females and male dogs as well. In spayed females, the onset usually starts 2 to 3 years after an uneventful spay but can occur weeks to years after an ovariohysterectomy. Nocturia appears to be the most common complaint from owners. UI can be daily or episodic and can range from mild to very severe. The incidence is 5.1% to 9.7% of spayed dogs. If only large-breed dogs are considered, the incidence approaches 12.5% of spayed females.

It has been theorized that because estrogen exerts a permissive effect on the α-receptors of the internal urethral sphincter, removal of estrogen results in decreased responsiveness of the muscle to sympathetic stimulation and decreased internal sphincter tone.

Although urethral incompetence occasionally occurs in male dogs, it has not been definitively associated with castration. However, a definitive diagnosis can be obtained only by urodynamic tests. A urethral pressure profile (UPP) evaluates the pressure along the entire length of the urethra; a cystometrogram evaluates the detrusor reflex, bladder fill volumes, and compliance.

Medical management of USMI includes the use of drugs aimed at improving urethral pressures via the α1-adrenoceptors (α1-AR), such as phenylpropanolamine (PPA). The therapeutic benefit is usually seen within 2 to 3 days. The oral dosage is 1 to 2 mg/kg PO q8-12h. Adverse effects in dogs receiving α-agonists can include restlessness, anxiety, hypertension, increased intraocular pressure and hepatic glycogenolysis. PPA is not recommended for patients with cardiac disease, hypertension, kidney disease, glaucoma, or diabetes mellitus.  If required for dogs with kidney disease, lower dosages should be administered and the patient’s blood pressure should be monitored regularly, ideally 2 to 4 hours post–PPA administration.

In cases that do not respond adequately to α-adrenergic agonists, combination therapy with estrogen supplementation can be attempted. Both drugs should initially be given at the recommended dose; if the drugs are effective, the α-agonist should be reduced to the lowest effective dose. Estrogens are thought to sensitize the α1-AR to NE and indirectly result in an improvement in the closure pressure, but the exact mechanism of action of these drugs is unclear. Diethylstilbestrol (DES) is a synthetic estrogen that has been successfully used to treat spay-related incontinence. The oral dosage is 0.5-1.0 mg/dog PO q24h for 3 to 5 days, then q7d. Adverse effects include vulvar or mammary swelling, attractiveness to males, lethargy, vomiting, and diarrhea. It causes prostatic metaplasia in males. Although estrogens can lead to bone marrow suppression, this has not been reported at recommended doses. DES shouldn’t be used in cats and intact female dogs. Another estrogen compound, Estriol can also be used for the medical management of USMI. The oral dosage is 2 mg/dog PO q24h for 14 days, then reduced in 0.5-mg increments q7d to lowest effective dose. A complete blood count (CBC) should be monitored periodically in all dogs receiving estrogen therapy.

Imipramine, a tricyclic antidepressant, inhibits norepinephrine reuptake at the neuronal synapse, thereby increasing sympathetic tone. Although this drug may be useful in treating refractory cases of sphincter incompetence, there has been little research to document its effectiveness. Potential side effects, including sedation, aggression, constipation, hypotension, and tachycardia, may limit its use. The oral dosage for dogs is 5-15 mg/dog PO q12h and the oral dosage for cats is 2.5-5 mg/cat PO q12h.

Colposuspension is a procedure in which the urethra and vagina are surgically moved cranially so that the bladder neck is relocated to an intraabdominal position. Reported long-term continence rates for this surgery range from 13% to 53%, although a significantly larger percentage of owners reported partial relief from urine dribbling. Submucosal urethral bulking agent such as polydimethylsiloxane is available for animals that are refractory to medications. In this procedure, dogs are anesthetized and three to four deposits of the bulking agent are injected in a circular fashion approximately 1.5 cm distal to the trigone via the cystoscope. If dogs are nonresponsive to medical therapy, urethral occluders can also be considered. The occluders can be surgically placed around the proximal third of the urethra; they act as an external occluder to maintain continence. 

1.      Ectopic Ureter (EU)

Ureteral ectopia is a congenital abnormality characterized by termination of one or both ureters at a point distal to the bladder neck. The flow of urine bypasses the bladder neck, and affected animals typically leak urine from birth. In cases of unilateral ectopic ureter, normal urine voiding is reported because one ureter is properly emptying into the bladder. In bilateral cases, normal urination may not occur. Eighty percent to 89% of canine ectopic ureters occur in females, and at least one-quarter of these cases are bilateral.  Although ectopic ureters have been reported in cats, they are probably rare. Breeds such as soft coated wheaten terriers, Labrador & Golden retrievers, Siberian husky, English bulldog and Newfoundland have an increased incidence of ectopic ureters. Dogs with ectopic ureters often have urinary incontinence prior to neutering, although this may be misinterpreted as poor housetraining by the owners. EUs are uncommon in male dogs and, if present, affected patients may have few or no clinical signs or present with clinical signs at an older age. EUs are extremely rare in cats.

A diagnosis of EUs can be made by excretory urography, fluoroscopic urethrography or ureterography, abdominal ultrasonography, cystoscopy, helical computed tomography (CT), or a combination of these diagnostic procedures. The latter two are reported to be the most sensitive diagnostics for confirming the presence of EUs. Complete continence is achieved after surgical correction in approximately 65% of cases. It has been reported that dogs weighing less than 20 kg have a better outcome postoperatively.

2.      Overactive bladder (OAB) / Detrusor instability

Detrusor instability (hyperspasticity) is characterized by sudden awareness of an urgency to urinate combined with an involuntary bladder contraction. Clinical presentation includes nocturia, pollakiuria, urgency, and incontinence. Instability secondary to infection, neoplasia, or uroliths is called urge incontinence.  In some cases, an underlying inflammatory condition is not found and the condition is referred to as idiopathic detrusor instability. The first step in the diagnosis of this condition involves ruling out an underlying cause. As with all cases of urinary incontinence, thorough physical and neurologic examinations and patient history are essential. Urinalysis with microscopic analysis and culture is also vital, as is ultrasonography of the bladder wall and contents. Definitive diagnosis of idiopathic detrusor instability involves conducting cystometrography.

Oxybutynin is an anticholinergic agent that may help stop bladder spasms and promote urine retention. The oral dosage in dogs is 0.2 mg/kg PO q8-12h. The oral dosage in cats is 0.5-1.25 mg/cat PO q8-12h. Adverse effects may include diarrhea, constipation, hypersalivation, urine retention, and sedation. It should be used with caution in patients with hypotension.

A tricyclic antidepressant drug, Imipramine may increase bladder relaxation. Imipramine is considered for dogs that have urge incontinence secondary to behavioral problems. However, it should only be used when behavioral modifications have been unsuccessful, and discontinued when clinical signs improve.

1.      Other conditions causing incontinence

Malposition of the urinary bladder within the pelvis (i.e., “pelvic bladder”) is often associated with urinary incontinence. The bladder is ordinarily positioned in the abdomen. In affected patients, the bladder neck and some portions of the body are located in the pelvic canal. It is not clear why 50% of dogs with this condition are incontinent. This condition usually occurs in large-breed female dogs, although it has also been reported in males. Contrast radiography typically shows an abnormally shaped bladder that fails to taper at the junction with the urethra, which is displaced caudally in the pelvic canal. Empirical treatment with phenylpropanolamine is thought to be helpful but unlikely to result in total resolution of signs. Some have recommended colposuspension in cases in which medical management is unrewarding.

Urovaginal and urethrorectal fistulas are uncommon causes of incontinence in dogs. Urovaginal fistula has been documented as a complication of ovariohysterectomy and occurs secondary to entrapment of the distal ureter by a ligature. Diagnosis is sometimes possible with intravenous urography but may require more invasive techniques, such as antegrade ureterography. Urethrorectal fistula may be congenital or the result of trauma. Although English bulldogs may have a genetic predisposition to develop the congenital form of this condition, it has been described in other breeds. Dogs with urethrorectal fistula typically present with persistent UTIs and passage of urine from the anus. The diagnosis can be made by cystography or retrograde urethrography under fluoroscopy. Successful surgical correction of both urovaginal and urethrorectal fistulas has been described.

Male dogs with urinary incontinence pose a more difficult challenge. Although a less common problem in males, less than 50% of male dogs respond to medical therapy, and the most successful treatment is PPA. One possible reason for this is misdiagnosis of dogs with USMI when in fact they have overflow incontinence from urethral sphincter dyssynergia or functional urethral obstruction. Measurement of a residual urine volume is essential to rule this out. Testosterone cypionate has had some anecdotal use in males with USMI and may provide some improvement. Testosterone is thought to improve urethral smooth muscle tone. The dosage of testosterone cypionate in dogs is 2.2 mg/kg IM q30-60 d. Should be used with caution in patients with hepatic, cardiac or renal disease. The adverse effects include perineal adenoma and prostate enlargement. Urethral bulking agents may be placed antegrade through a cystotomy incision; however, there has not been formal evaluation of this procedure and its overall success rate is unknown.

A persistent increase in urethral closure pressure from a mechanical or functional obstruction can lead to secondary bladder dysfunction (atony) and overflow incontinence. Mechanical causes for urinary retention include urethroliths, bladder and/or urethral neoplasia, proliferative urethritis, urethral strictures and foreign bodies, urethral plugs, prostatic diseases (e.g., abscess, paraprostatic cyst, benign prostatic hypertrophy), and extraluminal urethral compressions. Functional obstructions can be seen with supra-sacral or brainstem disease (upper motor neuron bladders), urethral spasms that usually occur secondary to urethritis or a mechanical obstruction, and idiopathic functional urethral outflow tract obstruction, also known as detrusor-urethral dyssynergia (reflex dyssynergia). The diagnosis of overflow incontinence is made based on history, thorough physical and neurologic examination, and complete imaging of the urinary tract. Most animals will have a history of intermittent to persistent stranguria prior to the UI. Watching the animal void and assessing the residual urine volume is also helpful. Normal animals will have less than 0.5 to 1 mL/kg of urine remaining in the bladder after voiding. Plain radiography, cystourethrography, and cystoscopy can all be beneficial to evaluate the patient for mechanical obstructions.

The diagnosis of idiopathic functional urethral outflow tract obstruction (detrusor-urethral dyssynergia) is usually made when all other causes for the increased urethral closure pressure have been excluded. This disease usually occurs in large-breed male dogs, both castrated or intact. Treatment for mechanical obstructions is to remove the obstruction, if possible. Urethral stones can be removed via surgery or holmium: YAG laser lithotripsy. Bladder and urethral neoplasia, usually transitional cell carcinoma (TCC), should be treated with piroxicam or another nonsteroidal anti-inflammatory drug (NSAID); other chemotherapeutics such as mitoxantrone or platinum compounds may improve survival.

For idiopathic, functional, urethral outflow tract obstruction, α1-adrenoceptor antagonists such as prazosin can be used to help relax the internal urethral sphincter. The dosage of prazosin in dogs is 1 mg/dog PO q8-12h for dogs weighing less than 15 kg and 2 mg/dog PO q8-12h for dogs weighing more than 15 kg. The dosage in cats is 0.25-1 mg/cat PO q8-12h.

Tamsulosin is useful in treating ureterospasm associated with ureteritis or ureteroliths. Tamsulosin is a selective α1a-adrenergic blocker that is more selective to the urinary tract (i.e., prostatic urethra, bladder neck) and thus has more limited cardiovascular side effects. The dosage in dogs is 0.1-0.2 mg/10 kg (up to 0.4-mg total dose) PO q12-24h. The dosage in cats is 0.004-0.006 mg/kg PO q12-24h.

Parasympathomimetics can be started if secondary bladder atony is also present. Bethanechol, a cholinergic agent, that directly stimulates muscarinic receptors in the detrusor smooth muscle of the bladder. can help restore bladder tone and facilitate bladder emptying. The dosage in dogs is 2.5-25 mg/dog PO q8h. The dosage in cats is 1.25-7.5 mg/cat PO q8h.  In severe cases, a tube cystotomy, indwelling urinary catheter, or urethral stent may be needed for urine evacuation.

Conclusion

Urinary incontinence can be frustrating for the animal owners. Fortunately, its easy to diagnose in most cases and managed medically. Few cases may require intensive measures.

 

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References

1. Acierno, Mark J., and Mary Anna Labato. "Canine incontinence." Compendium 28.8 (2006).

2.      Byron, Julie. "Canine Urinary Incontinence." American Veterinarian 3.5 (2018).

3.     Drippy Dogs: Causes and Treatment of Urinary Incontinence by Julie K. Byron, DVM, MS, DACVIM (NAVC Conference 2014 Small Animal)

4.    Drugs used to treat urinary incontinence in dogs and cats by Julie K. Byron, DVM, MS, DACVIM (Plumbs Therapeutic Brief, 2017).

5.     Nelson, Richard W., and C. Guillermo Couto. Small animal internal medicine-E-book. Elsevier Health Sciences, 2019.