FELINE LOWER URINARY TRACT HEALTH METABOLISM AND STRESS Margie Scherk, DVM, Dip ABVP (Feline Prac7ce) Vancouver, Canada Lower urinary tract disorders are common in cats. In previous decades, the focus of study has been on causes and management of crystalluria. As struvite crystalluria was successfully addressed through nutri7onal changes resul7ng in urine acidifica7on, the frequency of calcium oxalate crystalluria increased. This encouraged emphasis on urine rela7ve supersatura7on (RSS), concentra7on and a ph neutrality. Nevertheless, cats s7ll present with characteris7c lower urinary tract signs (LUTS), namely dysuria, pollakiuria, hematuria, stranguria and periuria. The cause of approximately 65% of nonobstruc7ve lower urinary tract disease is of unknown despite appropriate diagnos7c tes7ng. (Possible causes of LUTS are shown in Figure 1. A diagnos7c approach to cats with lower urinary tract signs is shown in Figure 2.) These pa7ents are described as having an idiopathic cys77s (IC). It is likely that this syndrome is mul7factorial even within the same cat. The course of human inters77al/idiopathic, including inters77al cys77s, is known to be impacted by stress. There is evidence that there are immunological and neuroendocrine components in our feline IC pa7ents as well. Studying feline idiopathic cys77s (FIC) is extremely challenging not only because of its mul7factorial nature, but also because clinical signs are self-limi7ng. In approximately 91% of cats, evidence of discomfort resolves within 7 days without treatment. Subsequent episodes are also acute in nature and occur once or twice a year. As cats get older, the frequency and severity of the flare-up decreases. A small number of cats experience chronic persistent disease las7ng weeks to months. Inflamma7on associated with each incident may result in func7onal or mechanical obstruc7on. The first may be caused by urethra swelling, spasm, or reflex dyssynergia, while accumula7ons of inflammatory debris or the forma7on of matrix plugs can cause mechanical obstruc7on. Urachal diver7culae are a possible sequelae to FIC. What causes the inflamma7on in non-obstructed LUTD? Many studies have a]empted to answer this ques7on yet results have been disappoin7ng. Infec7ous agents, dietary causes (mineral composi7on, RSS and urine ph), neurogenic, anatomic, trauma7c, neoplas7c and iatrogenic e7ologies are all implicated in some individuals, but the largest category remains idiopathic in origin.
Buffington and colleagues have inves7gated the problem from another angle asking whether a suscep7ble individual might develop FIC if they are in a provoca7ve environment. Indeed, similar to the human model of IC, he found that affected cats have structurally altered adrenals, more reac7ve somatosensory spinal tracts and a larger pon7ne locus coeruleus (LC, the most important source of norepinephrine in the CNS) This suggests that pa7ents with IC have increased sympathe7c nervous system (SNS) ac7vity even during periods without clinical signs. He has reviewed published epidemiologic data regarding the role of environment and its physiologic effects on risk for disease, especially in suscep7ble individuals. External influences include excessive body condi7on, decreased ac7vity, being restricted to eliminate in a li]er box, being strictly indoors, reloca7on of home, living with other cats and weather changes. Stressors (internal/perceived influences) that affect different individuals to a greater or lesser degree include an impoverished environment, lack of s7mula7on, noise, restraint, and lack of control over his/her environment (including meals). The stress response invokes changes in immune, neurologic and vascular status, all of which can coopera7vely result in inflamma7on. With sufficiently severe stress, sensory input and inflammatory mediators s7mulate the hypothalamicpituitary-adrenal axis (HPAA) and the aforemen7oned pon7ne LC norepinephrine system. With chronic s7mula7on, over 7me normal control is lost and affected individuals overreact physiologically to threatening or disrup7ve situa7ons. Modified from Buffington CAT, Westropp JL, Chew DJ. From FUS to Pandora syndrome: Where are we, how did we get here, and where to now?. J Feline Med Surg. 2014;16(5):385-94. Buffington and co-workers also iden7fied that cats, as humans, with IC frequently have co-morbidi7es and has called this the Pandora Syndrome. He suggests that the bladder, rather than being the perpetrator of the LUTS, may be a vic7m of the systemic process associated with the sensi7zed central stress response system. Comorbid disorders include behavioural, endocrine, dermatological, respiratory, cardiovascular, and gastrointes7nal problems. FIC does not necessarily precede the other condi7ons. In
humans, the effects of chronic in utero stress on the health of the offspring are well documented. It may well be that gene7c and similar epigene7c events contribute to the suscep7bility of an individual making them at risk should they be exposed to provoca7ve events. MANAGEMENT OF CATS WITH FIC Evalua7ng the efficacy of therapies for FIC is very difficult because of the waxing-waning nature of the disorder. Stress reduc7on appears to be a cornerstone for managing cats afflicted with FIC. Addressing environmental needs is essen7al (not op7onal) for op7mum wellbeing of the cat. Environmental needs include those rela7ng not only to the cat s physical surroundings (indoors or outdoors; in the home environment or at the veterinary prac7ce) but also those affec7ng social interac7on, including responses to human contact. Cats need to have mul7ple and separate loca7ons for each resource (food, water, clean li]er, toys, stable scratching surfaces, perches and res7ng areas). The overview of a therapeu7c and management approach to a cat with LUTS is shown in Figure 3. It is essen7al that cats are able to express their natural behaviours. Cats use olfactory and chemical informa7on to evaluate their surroundings and maximize their sense of security, comfort and feel in control of their surroundings/environment. Deposi7ng pheromones through cheek and paw pad marking as well as urine is key for a cat s sense of control. In some situa7ons, when a cat is marking with urine, it may be possible to get the cat to make a less offensive mark (from a human perspec7ve). Cheek marking wall corners may be encouraged by using Feliway and not washing the cat s natural oils off walls and furniture. Likewise, providing secure, stable scratching surface placed in the loca7on being urine marked, may result in the cat scratching and marking in that manner rather than spraying. The AAFP and ISFM Feline Environmental Needs Guidelines is an excellent resource freely available from: (jfm.sagepub.com/content/15/3/219.full.pdf+html). Pheromone Use Feliway TM is a synthe7c analog of a feline facial pheromone that is thought to increase emo7onal stability. Its use in the reduc7on of inappropriate urina7on needs to be studied further. Studies done to date have shown a reduc7on in urine marking of less than three months dura7on of over 96%. In cats who had been marking for four months or longer, there was a reduc7on of marking in 91% of cats aner 35 days of environmental treatment. A third study showed that while there was a significant reduc7on in all households in which Feliway TM was applied, 2/3 of the households s7ll experienced some marking. The product is sprayed directly on places soiled by the cat and also any prominent ver7cal loca7ons in the environment. A daily applica7on is necessary un7l the cat is noted to exhibit facial rubbing on the site. If the cat does not exhibit facial rubbing, then daily applica7on to the environment should be con7nued for one month. Plug-in diffusers provide a constant, slow release of pheromone covering an area of 500 to 700 square feet (50-70 m 2 ), but must not be covered, placed behind a door or under furniture. Diet and Drugs Feeding a diet that produces dilute urine with a neutral ph seems to help cats have fewer recurrences of FIC or any type of lower urinary tract disease. Canned food helps to ensure that the urine is dilute, making it less concentrated (hence, less irrita7ng) and reducing the chance that crystals can form. Having plenty of fresh water available in mul7ple places in a form the individual cat likes will encourage drinking. Some cats prefer drinking from a recircula7ng water fountain, others prefer wide bowls. Feeding a diet that has omega-3 fa]y acids along with an7-oxidants may also provide beneficial an7- inflammatory effects. Finally, being consistent both in 7me of feeding as well as diet being fed is very important in reducing stress.
Many drugs have been used to try to reduce the reoccurrence of FIC. Amitriptyline may be helpful in some cats if it is given on an ongoing basis. It is an an7depressant and agent that stabilizes mast cells which may degranulate in some individuals with FIC. Glucosaminoglycans have also been studied and have variable, but generally poor, results. Best results appear to occur with diet, environmental and stress management rather than drug therapy. SUMMARY Lower urinary tract disorders are common in cats. Once appropriate diagnos7cs have ruled out direct causes, for most cases of non-obstruc7ve LUTD, a more global approach needs to be taken, looking at and addressing the role of the cat s external and internal environments. Figure 1: Possible causes of lower urinary tract signs in cats with or without co-morbid condi7ons (Pandora Syndrome) (from Chew D, Buffington CAT, FLUTH Symposium 2014)
Figure 2: Diagnos7c approach to cats with lower urinary tract signs (from Chew D, Buffington CAT, FLUTH Symposium 2014
Figure 3: Algorithm showing a therapeu7c and management approach to a cat with lower urinary tract disease
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