Urinary incontinence (non-neurological) in the dog and cat

Urinary incontinence consists in the loss of voluntary control of urination. It is a condition which is often overestimated and which requires a complex approach in terms of differential diagnosis. A careful medical history directed at the problem, physical examination, blood and biochemical tests, urinalysis and urine culture are essential parts of a diagnostic procedure that has to differentiate those conditions which, causing pollakiuria, dysuria or polyuria, could easily be confused with and thus reported as incontinence.

URINATION

Urination depends on the coordinated action the sympathetic, parasympathetic, somatic and central parts of the nervous system. This coordination seems to occur at the pontine micturition centre (Barrington’s Nucleus), which receives the sensory stimulus and causes urination to begin. The filling phase of the bladder is controlled primarily by the sympathetic nervous system. The hypogastric nerve (which originates from L1-L4 in the dog and L2-L5 in the cat) stimulates the beta receptors of the bladder detrusor muscle, causing it to relax; in addition, through stimulation of the alpha-1 receptors in the bladder neck and in the internal urethral sphincter, it causes these to contract, making it possible to maintain continence. This mechanism is also assisted by the pudendal nerve (S1-S3), which supplies somatic innervation to the striated muscle of the external urethral sphincter; by stimulating the nicotinic cholinergic receptors, it causes this latter to contract, thus “strengthening” the closure system, when necessary.

The afferent information is transmitted by the bladder primarily through the pelvic nerve, though additional sensory information can be transmitted through the hypogastric nerve and the sympathetic system. The majority of the fibres involved are Aσ and C fibres. Aσ fibres are myelinic, with a threshold of around 5-15 cm H₂0, and they transmit the information regarding bladder filling. The majority of C fibres are amyelinic; they transmit the nociceptive stimuli. Both are found in the serous and muscular layers and in the structure of the bladder urothelium[1].

The emptying phase of the urination process, on the other hand, is controlled primarily by the parasympathetic nervous system. The pelvic nerve (S1-S3) stimulates the muscarinic cholinergic receptors of the bladder detrusor, causing a contraction that increases the intravesical pressure. At the same time, the sympathetic stimulation is inhibited at the pontine centre, causing the internal and external urethral sphincters to relax. Urination occurs when the intravesical pressure exceeds the pressure of sphincter closure[2].

INCONTINENCE IN THE YOUNG DOG

In the young dog, incontinence can be the expression of congenital disorders, which, though rare, should always be considered. To establish a definitive diagnosis, such disorders require haematology, blood chemistry and microbiology, as well as the use of several diagnostic imaging techniques. A careful medical history and physical examination are essential. The greatest risk is underestimating the event, attributing the problem to immaturity or behavioural problems ascribable to inappropriate urination.

ECTOPIC URETER
Ureteral ectopia, though rare, is the most frequent cause of incontinence in the young dog. In the cat, this condition is even rarer. The cause is unknown, and although it is presumably hereditary in nature, this has not yet been proven. The condition occurs more frequently in females than in males, and is reported especially in: Siberian Huskies, Golden Retrievers, Labrador Retrievers, Newfoundlands, English Bulldogs and West White Highland Terriers[3].

Ureteral ectopia can be unilateral or bilateral, extramural or intramural. The clinical signs will depend on the type present. The extramural ectopic ureter bypasses the trigone of the bladder and inserts more distally in the urethra, vagina or vestibule in the female, and in the ductus deferens in the male. The intramural ectopic ureter inserts into the trigone, but then “tunnels” into the urethral wall to open distally. Ureteral ectopias are often associated with other congenital abnormalities, including: agenesis/hypoplasia/renal malformations, hydroureter, ureterocoele, pelvic bladder, patent urachus, vestibulovaginal stenosis.

Animals may present with a continuous or intermittent urinary incontinence and the act of urination may be preserved. Wet hair and colour alterations in the perivulvar and perineal areas, dermatitis, urine burns and severe vulvovaginitis may be observed during the general physical examination. Urinary tract infections are found in 64% of patients. In this case, both the lower and the upper urinary tract may be involved.

The diagnosis is generally made through excretory urography or CT with contrast. The condition is solved through surgery: transposition of the ectopic ureter into the bladder or excision of the ectopic ureter and homolateral nephrectomy in case of severe diseases secondary to the ectopia (hydronephrosis, hydroureter, pyelonephritis). Therapeutic success is estimated in around 50% of the cases, mainly because of under-diagnosed bilateral ectopias and/or the presence of additional disorders causing incontinence, such as:urethral sphincter mechanism incompetence (USMI) or bladder hypoplasia.[4]

CONGENITAL URETHRAL SPHINCTER MECHANISM INCOMPETENCE
Congenital urethral sphincter mechanism incompetence (USMI) is prevalent in large-sized female dogs. Leakage of urine is generally more abundant compared to that occurring with the ectopic ureter. Female dogs leak urine while sleeping (enuresis) or when lying down. The urethra may be shorter or sometimes absent (in the cat). In male subjects, the urethra may have dilatations or diverticula.  Generally speaking, diagnostic imaging does not provide information, except for the presence of a pelvic bladder. The majority of female dogs become continent with the first heat. Prepubertal sterilisation and the use of oestrogen hormones are discouraged. The use of alpha-adrenergic agents is instead recommended, which can be continued after the first heat. The prognosis in male subjects depends on the concomitant anatomical abnormalities and is generally worse than in females.

PERSISTENT URACHUS
The urachus is the canal that connects the apex of the foetal bladder to the umbilicus. It atrophies, and at birth it is no longer functional. If the atrophy is incomplete, the duct remains patent and at birth leakage of urine through the umbilicus can be observed. A cystography can highlight the abnormality, which has to be corrected surgically.

BLADDER HYPOPLASIA
The diagnosis of bladder hypoplasia subjective and it is not possible to determine if the patient is affected by a true hypoplasia or by the lack of development of a normal organ. Bladder hypoplasia is detected with a retrograde cystography, showing that the organ fills up with a small amount of contrast material. It is important to exclude other causes of incontinence that might have led to an inadequate bladder development, because of a constant lesser degree of filling of the organ, such as for example the presence of an ectopic ureter. In these cases, the resolution of the “primary” cause may allow the recovery of a normal bladder volume. Otherwise, the use of anticholinergic drugs might be indicated which, by relaxing bladder muscles, could lead to an increase in the filling volume before urination.

PSEUDOHERMAPHRODITISM
In pseudohermaphrodites, incontinence occurs already in the early phases of life and may be accompanied by obvious clinical signs, including: haematuria and dysuria caused by secondary bacterial infections. The incontinence is due to the retention of urine in abnormal connections between the urethra and the genital tract, with resulting obvious leakage of urine. The diagnosis can be confirmed with contrast radiography (retrograde urethrography or excretory urography); the condition is reversible through surgical correction of the anatomical malformations[5].

ACQUIRED INCONTINENCE

URETHRAL SPHINCTER MECHANISM INCOMPETENCE (USMI)
In the female dog, the relationship between urinary incontinence and sterilisation has been known for some time. The resulting oestrogen deficiency certainly contributes to a decrease in the competence of the urethral sphincter, as occurs in women, where, similarly, a considerable increase in the incidence of incontinence after menopause is detected.

The presence of oestrogen receptors in the urethral sphincter[6], their function of sensitisation of the alpha-adrenergic receptors to the action of catecholamines and the presence of oestrogen receptors in the areas of the brain involved in the urination process[7] all underline the importance of oestrogen hormones in maintaining the competence of the urethral sphincter.

Nevertheless, the understanding of the aetiopathogenesistook years and is still evolving.This is due in part to the fact that incontinence after gonadectomy occurs with extremely variable timing: from right after sterilisation up to 10 years after surgery (average 2.9 years). Seventy-five percent (75%) of subjects become incontinent in the first three years after the operation.

There are differences in the incidence reported by the different authors: from 5%[8] to 20%[9]. The incidence is greater in large-sized female dogs, weighing > 20 kg[10]. Dobermanns and Boxers are among the breeds most represented. Although in the past it was thought that ovariohysterectomised bitches were more likely to become incontinent than ovariectomised ones, because of adhesions of the neck of the bladder to the uterine stump, more recent studies have reported a similar incidence in the two groups, regardless of the type of operation[11].

Incontinence occurs less frequently in female dogs spayed before their first heat; in these subjects, however, the clinical sign is more severe and treatment is more difficult.

Additional risk factors are: excess body weight or obesity; some authors report tail docking[12] as a predisposing factor.

Clinical signs
Female dogs often arrive at the general physical examination with their bottoms wet with urine and coat colour changes in the perivulvarand perinealareas, where dermatitis or actual urine burnsare sometimes observed. Bitches frequently experience leakage of urine while sleeping, sitting or lying down. When standing and/or moving there may be a trickle of urine from the vagina, which may be even more noticeable when the dog moves, jumps, barks or during examination of the external genitals. Systemic clinical signs and dysuria are absent. Haematology and blood chemistry are within the normal range. It is advisable to verify the absence of urinary tract infections through urinalysis and urine culture, given the greater predisposition to ascending infections.

Pharmacological therapy
Alpha-adrenergic agents. Alpha-adrenergic drugs are effective because around 50% of the urethral closure pressure is generated by the sympathetic nervous system. The alpha-1 receptors are found on the neck of the bladder and on the proximal urethra; stimulation of these receptors induces an action on the urethral smooth muscle. The effectiveness of this pharmacological treatment is estimated to be around 75%.

The most often used drug is phenylpropanolamine (1-1.5 mg/kg BID or TID). Phenylpropanolamine is an alpha 1-agonist that acts on the receptors responsible for continence. The side effects are due to the fact that alpha-1 receptors are also found in other organs and in the vessels and these adverse events occur in around 9% of cases: anorexia, vomiting, dry mucous membranes, hypertension, hyperreactivity. A repeated monitoring of blood pressure has been recommended, even though hypertension has not been demonstrated in prospective studies conducted on incontinent dogs treated with phenylpropanolamine at the therapeutic doses. The side effects are generally reversible with the suspension of treatment. Episodes of stroke and sudden death have been reported in humans. In the dog, cases of sudden death have been reported in cases of overdose[13].

Ephedrine is a less selective agonist. This drug also acts on beta receptors and is therefore the cause of greater side effects. It gives rise to dependence and is therefore less often used.

Oestrogen hormones. Oestrogen hormones sensitise the alpha-adrenergic receptors to the action of endogenous and exogenous catecholamines. They can be administered in conjunction with alpha-agonists and act in synergy with them. Oestrogen hormones are reported to be effective in around 65% of cases.

The active substances used currently are oestriol or conjugated oestrogens. No specific effective dose vs. body weight ratio has been found for either of them, so the dosages and the therapeutic plans are individual.

Oestriol is administered in doses ranging from 0.5 mg up to 2 mg/day per dog for 5-7 days until therapeutic efficacy is reached; subsequently, the dose and/or the frequency of administration should be reduced as needed to maintain sphincter competence[14].

Conjugated oestrogens have been administered starting from 0.3 mg/day per dog for 7-15 days. In case of therapeutic inefficacy the doses may be increased (0.625 mg – 1.25 mg – 2.5 mg) until reaching competence. The dose and/or frequency of administration are modified until reaching the minimum dose useful for maintenance. Possible side effects include vulvar tumefaction and attraction of male dogs.

GnRH analogues (depot implants).The use of these implants is based on the consideration that oestrogen deficiency is not the only hormonal change that occurs following ovariectomy. Castration causes the absence of a negative feedback (given by the gonadal hormones) on the hypothalamic-pituitary system, leading to an increase in FSH and LH which, one year after sterilisation, reach concentrations even 10 times higher than those prior to sterilisation. Elevated gonadotropin levels were therefore presumed to be the cause of incontinence. The administration of GnRH analogues in depot preparations (which maintain high GnRH levels in the blood for weeks) should therefore lead to the progressive desensitisation of the pituitary GnRH receptors, with consequent reduction in LH and FSH levels.

The observation that the gonadotropin levels found in subjects that responded to the treatment did not differ from the level found in subjects resistant to the treatment itself called however for further reflections. A direct action of GnRH on the lower urinary tract was thus hypothesised. The demonstration of the presence of GnRH receptors (as well as FSH and LH) in the lower urinary tract is supportive of this last hypothesis. Treatment with GnRH analogues turned out to be effective in around 50% of cases[15][16].

Surgical treatment of USMI
In cases resistant to pharmacological treatment, and having first excluded diseases that could be a cause of polyuria, the following surgical techniques can be used: urethropexy, colposuspension and submucosal injection of collagen under endoscopic guidance.

Colposuspension was the technique described most. Initially, the results appeared relatively promising, allowing to achieve a short-term continence in 50-75% of patients[17]. The long-term continence results were less satisfactory.

With urethropexy, continence is attained in 56% of the cases and improvement in clinical conditions in 27% of cases[18].

Undoubtedly, the injection of collagen is a quite competitive technique, in that it is a minimally invasive method. When used as a sole treatment the technique is effective in 68% of the cases; this percentage increases to 83% if it is combined with pharmacological treatment. Around 12 months after the operation, however, a worsening of clinical conditions is observed. This is due not so much to the reabsorption of the collagen deposits, which remain obvious in the histological sections, as to their flattening[19].

As regards the long-term results of the endoscopic injection of collagen, it can be affirmed that after an average period of observation of 33 months, the reported final probability of success is of 68%[20].

USMI in the male dog. While in the female dog USMI accounts for around 44% of the cases of incontinence, in the male dog the percentage decreases to 13%.

Around half of the male dogs with USMI are intact: the close relationship (found in females) between gonadectomy and urinary incontinence is not present in the male. Unlike females, which often manifest incontinence while sleeping or lying down, in males incontinence is a more constant clinical sign which, in addition, responds less to pharmacological treatments (only 50% of the cases respond to the use of phenylpropanolamine).

In the course of USMI, in the male, a pexy of the deferent ducts has been proposed as the surgical therapy to be used in subjects resistant to pharmacological treatment; the deferent ducts are attached to the abdominal wall to obtain an effect similar to that attained through colposuspension in females.

However, the result does not appear to be comparable to that attained following the injection of collagen. Collagen deposits are deposited in the pars prostatica, as this is the part mainly responsible for urinary continence in the male. Nevertheless, the injection of collagen into the urethral submucosa of the pars prostatica is a risky procedure, since the prostate is under the influence of testosterone[21]. For this reason, it is recommended to neuter the male (if intact) in time.

URGE INCONTINENCE
Urinary incontinence may be caused by bladder hyperactivity during filling, which causes involuntary detrusor contractions. The cause of this decrease in detrusor compliance and thus of its involuntary contractions is not of neurological origin, but secondary to diseases of the lower urinary tract: infections, inflammations, urolithiasis, bladder tumours, cervico-urethral obstructions. In the absence of an identifiable cause, it is defined as idiopathic detrusor instability.

Urination becomes more frequent and less abundant. The bladder contracts constantly, both during the day and at night, and the need to urinate is sudden, urgent and uncontrolled.

Treatment involves resolution of the primary cause and the use of antimuscarinic drugs.

The use of these drugs is reserved for urge incontinence or for cases of USMI resistant to pharmacological treatment. These active substances increase the filling capacity of the bladder, counteracting the involuntary contractility of the detrusor and the consequent inappropriate leakage of urine.

These treatments may be combined with alpha-adrenergic agents or oestrogen hormones. The active substances include oxybutynin (0.2 mg BID or TID), flavoxate HCl (10 mg/kg BID) and terazosin. The contraindications include: pyloric and duodenal obstructions, partial bowel obstructions, glaucoma.

OVERFLOW INCONTINENCE
Some cases of incontinence may be caused by an increase in the urethral closure pressure. Indeed, some mechanical causes can lead to urinary retention. These include: uroliths or urethral plugs, bladder and/or urethral neoplasias, urethral stenoses and proliferative urethritises, prostate disorders causing a mass effect (abscesses, paraprostatic cysts, etc.). Functional urethral obstructions may cause spasms that can be secondary to inflammatory processes and bladder sphincter dyssynergia. These disorders can cause relaxation of the bladder, with consequent detrusor malfunction and atony and thus “overflow” incontinence[22].

Persistent overdistension of the bladder may contribute to the loss of functionality on the part of the detrusor. In fact, the smooth muscle fibres of the detrusor coordinate the contraction via tight junctions, whose expansion or destruction leads to a deficit in neuromuscular conduction, giving rise to an uncoordinated, weak or even absent muscle contraction[23].

Various clinical signs may be present as a result of the pathological process that caused the mechanical or functional obstruction: haematuria, pollakiuria and strangury are frequently reported in the medical history. On palpation, the bladder presents with a high degree of repletion and with a flaccid consistency. The perineal reflexes are maintained.

The diagnosis must be based on radiologic or endoscopic examinations in order to confirm the presence of mechanical obstructions. Urodynamic studies are reserved for investigations on functional obstructions.

Treatment involves the removal of the causes of mechanical obstruction and catheterisation to keep the bladder empty.

In order to relax the internal urethral sphincter the use of alpha-1 antagonists is indicated, such as: phenoxybenzamine (0.25 mg/kg BID or TID orally) or prazosin (1 mg/15 kg BID or TID orally). The use of diazepam might also be beneficial.

Only once this effect on the urethra has been obtained, the use of bethanechol(5-25 mg every 8 hours) might be indicated to restore detrusor muscle tone and facilitate its contraction and thus bladder emptying. In the most severe cases, cystotomy tubes or urethral stents might be considered to guarantee evacuation.

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