Micturition disorders in dogs and cats (Proceedings)

Physiology

Micturition is controlled by a combination of autonomic and somatic innervation. Sympathetic innervation to the bladder via the hypogastric nerve is composed of preganglionic fibers exiting the lumbar spinal cord from the L1-4 spinal cord segments and synapsing in the caudal mesenteric ganglion. Beta-adrenergic fibers terminate in the detrusor muscle; stimulation results in detrusor muscle relaxation and facilitates bladder filling. Alpha-adrenergic fibers innervate the smooth muscle fibers in the trigone and urethra, resulting in contraction of these muscle fibers to form a functional internal urethral sphincter. The normal storage phase is created by sympathetic autonomic domination, which results in detrusor muscle relaxation and urethral sphincter contraction created by alpha-adrenergic stimulation. Voiding is consciously inhibited by voluntary contraction of striated urethral muscles and is reflexly inhibited by a spinal reflex, which tightens the external urethral sphincter when there is a sharp increase in intra-abdominal pressure (e.g., barking, coughing, sneezing, or retching).

Parasympathetic innervation to the bladder is provided by the pelvic nerve, which arises from the sacral spinal cord segments S1-3. Parasympathetic innervation predominates during the voiding phase of micturition; stimulation of the pelvic nerve results in depolarization of pacemaker fibers throughout the detrusor muscle. The subsequent spread of excitation to adjoining muscle fibers through tight junctions of smooth muscle cells leads to contraction of the detrusor muscle. The sacral spinal cord segments S1-3 are also the source of the somatic innervation to the external urethral sphincter via the pudendal nerve. Stimulation of the pudendal nerve causes contraction of the striated skeletal muscle of the external urethral sphincter.

As the bladder fills and intramural tension exceeds the threshold, stretch receptors in the bladder send impulses via the sensory portion of the pelvic nerve through spinal cord pathways to the thalamus and cerebral cortex. When it is appropriate to void, impulses are sent from the cerebral cortex to the pons and then down the reticulospinal tract to the sacral nuclei. Parasympathetic activity via the motor portion of the pelvic nerve causes the detrusor muscle to contract and there is simultaneous inhibition of the sympathetic stimulation that closes the internal urethral sphincter. When the bladder has emptied, the normal sympathetic domination resumes; the outflow tract closes and the detrusor muscle relaxes for filling. The normal residual volume of urine after complete voiding is 0.2 - 0.4 ml/kg for both the dog and cat.

Clinical Signs and Diagnosis

Clinical signs associated with micturition disorders will often help one discern the underlying problem. In cases with small or normal-sized bladder disorders, urinary incontinence is usually caused by either increased detrusor contractility/irritability or decreased outflow resistance. Continuous urinary incontinence present from birth is likely associated with a congenital abnormality and may be a combination of anatomic and functional abnormalities. Incontinence associated with hematuria, pollakiuria, dysuria/stranguria, breaking of normal house training behavior usually indicates there is inflammation of the bladder and/or urethra (increased detrusor contractility/irritability). Urinary incontinence that is most pronounced when the patient is laying down, relaxed and/or asleep is most likely associated with urethral sphincter mechanism incompetence (decreased outflow resistance).

On the other hand, in cases with large, distended bladders, urine retention is usually caused by either decreased detrusor contractility or increased outflow resistance. Increased outflow resistance may be caused by anatomic obstruction (e.g., urethral calculi) or by functional outflow resistance (e.g., reflex dyssynergia). Reflex dyssynergia results in urine retention associated with increased outflow resistance during attempts to void due to failure of the alpha-adrenergic input to the internal urethral sphincter to be reflexly inhibited. Physical examination findings are often helpful in differentiating the underlying cause. A distended bladder that is easy to express is usually associated with decreased detrusor contractility. Distended bladders that are difficult to express are usually associated with increased outflow resistance; the ease of urethral catheterization can then often be used to differentiate anatomic from functional outflow resistance problems. Urethral catheterization is usually easy to perform in cases of increased urethral sphincter tone (e.g., reflex dyssynergia and upper motor neuron lesions). In contrast, passage of a urethral catheter is relatively difficult if anatomic obstructive lesions are present (e.g., urethral calculi and urethral masses).

Treatment – Big Bladder Disorders

Patients with lower motor neuron diseases resulting from sacral spinal cord lesions or from dysautonomia require expression or catheterization of the bladder at least three times a day. A urinalysis or examination of the urine sediment should be performed weekly and a urine culture should be initiated if there is any evidence of a urinary tract infection. Care should be taken to prevent urine scalding. A parasympathomimetic drug like bethanechol may be administered to increase detrusor contractility if urethral patency is assured (Table). Side effects of bethanechol include salivation, vomiting, diarrhea, or colic-like signs indicating intestinal cramping. These signs are normally noticed within an hour of drug administration, and if observed, the dosage should be decreased.

Management of detrusor atony requires bladder expression or intermittent urinary catheterization to keep the bladder empty for a period of days to weeks. A urinalysis should be performed every three to four days, and a urine culture and antibiotic sensitivity obtained if there is any evidence of urinary tract inflammation. Bethanechol may be administered to help increase detrusor contractility but only if the bladder can easily be expressed.

Management of patients with an upper motor neuron lesion to the bladder is dependent on the presence or absence of an automatic bladder. A reflex or automatic bladder will often develop 5 to 10 days after a spinal cord injury. Stretching of the bladder wall stimulates a local reflex arc that results in detrusor contraction. Prior to the development of the automatic bladder treatment should include aseptic catheterization at least three times a day since the increased outflow resistance makes these bladders difficult to express. Use of corticosteroids for neurologic disease may create polyuria, necessitating more frequent catheterization to prevent over distension of the bladder. Corticosteroids may also predispose patients to urinary tract infections. During the initial stages, urinalysis or examination of urine sediment should be performed every three to four days, and a urine culture and antibiotic sensitivity should be obtained if there is evidence of urinary tract inflammation (corticosteroids however will often mask signs of inflammation). Use of elevated racks or absorbent bedding is indicated, and petroleum jelly around the perineum or prepuce may minimize urine scalding.

After the development of an automatic bladder, the bladder should be palpated after urination to determine residual urine volume. Bladder expression or catheterization two to three times a day may still be required to minimize urine stasis. Urinalyses should continue on a bimonthly schedule (at least monthly if the animal is receiving corticosteroids), and owners should be instructed to bring in a urine sample if a change in urine color or odor is noted. Nursing care to prevent urine scalding should be continued.

Reflex dyssynergia will often respond to pharmacologic management, however therapeutic response may require several days. Drugs that are usually incorporated include phenoxybenzamine, a somatic muscle relaxant (e.g. diazepam), and, once the bladder is easily expressed, bethanechol may be added (Table). Intermittent urinary catheterization should be used as necessary to keep the bladder empty and combat detrusor atony, which may be caused by over distension of the bladder.

Phenoxybenzamine has a slow onset of action, and the dosage should be increased slowly at four-day intervals. The urinary stream is evaluated as an indication of drug effectiveness. If the stream is weak, but of normal diameter, bethanechol may be used to increase detrusor contractility, however, bethanechol must not be used until the functional urethral obstruction has been relieved. If the urine stream is intermittent or narrowed, increased dosage of diazepam and/or phenoxybenzamine is required. Because diazepam has a very short duration of action (approximately 1-2 hours when administered orally), administering diazepam 30 minutes prior to walking the animal will sometimes aid in the management of reflex dyssynergia. It may be several weeks before a correct combination of drugs is determined, and drug dosages may need modification over time. Periodic urinalyses are indicated to detect urinary tract inflammation/infection at an early stage. Hypotension is the major side effect of phenoxybenzamine administration, and the dosage should be immediately decreased if the animal shows any indication of weakness or disorientation. The dosage of phenoxybenzamine should only be increased if a favorable response is not observed after four days; rapid dose changes should be avoided. Nausea is a side effect, which can be minimized by administering the medication with a small meal. Glaucoma has been reported as a rare complication of phenoxybenzamine administration in human beings.

Treatment – Small Bladder Disorders

Treatment of urinary incontinence caused by urethral sphincter mechanism incompetence includes hormone replacement and/or the use of alpha-adrenergic drugs (Table). The usual induction therapy for estrogen-responsive incontinence is diethylstilbestrol (DES) orally, once daily for three to five days. The frequency of administration is then decreased to the lowest possible dose that will maintain continence. Some dogs can be successfully tapered to a very low maintenance dose of DES. Recently, estriol has bee evaluated as a daily or every other day estrogen replacement treatment in dogs. The loading dose recommended is 2 mg PO daily for 7 days followed by 0.5 – 2 mg/dog PO daily or every other day for maintenance. The long-term efficacy and safety of this regime has not been evaluated. Phenylpropanolamine may be used as an alternative drug or in addition to DES. Owners of dogs on phenylpropanolamine should be cautioned to observe their dog for hyper-excitability, panting, or anorexia, and to decrease the dose if these signs develop. While initially administered on an 8-hour schedule, in rare cases, the dose of timed release or precision release phenylpropanolamine can be decreased to a 12 or 24-hour schedule of administration. Careful observation by the owner for recurrence of signs usually indicates when the dose needs to be increased. Phenylpropanolamine is contraindicated in patients with systemic hypertension or mitral valve regurgitation. Dogs with increasing resistance to DES present the greatest worry since development of estrus-like signs and bone marrow toxicity are possible side effects of higher dose DES administration. Endocrine alopecia is another possible side effect of DES administration. If DES-resistant dogs are not on concurrent phenylpropanolamine, a trial should be instituted before the DES dose exceeds recommended levels (1 mg weekly).

Testosterone-responsive urinary incontinence is best managed by parenteral testosterone since most oral testosterone undergoes rapid hepatic degradation. Depository forms injected intramuscularly may be effective for four to eight weeks. Testosterone-responsive incontinence will frequently respond to phenylpropanolamine or ephedrine, and these drugs can be used as alternatives in male dogs with prostatic, perianal, or behavioral disease.

Smooth muscle relaxants and anti-cholinergics (e.g., aminoproprazine, oxybutinin, and propantheline bromide) have been used to decrease the detrusor spasticity associated with urinary tract inflammation, but their use should be reserved for those patients that do not respond to treatment of the primary disorder (e.g., antibiotics for bacterial urinary tract infections).

Correction of congenital defects depends on the nature and the extent of the defect. For example, a patent urachus and urachal diverticulum are surgically correctable, as are many forms of ectopic ureters. However, urethral sphincter incompetence may occur in conjunction with congenital abnormalities, and surgical correction of the disorder does not guarantee continence. Use of alpha-adrenergic drugs after surgery increases the percentage of successfully treated cases. In cases of anatomic urethral obstruction, the size and nature of the lesion can usually be determined by a contrast urethrogram. Prevention of renal damage secondary to urinary obstruction and relief of urinary obstruction to prevent detrusor atony from over distension are the main priorities in cases of urine outflow obstruction. If the obstruction is created by a urethral urolith, retropulsion of the urolith into the bladder may be successful. If the urolith cannot be moved by retropulsion, a temporary or permanent perineal urethrostomy may be necessary.