The role of stress in the pathogenesis of FLUTD

Feline Lower Urinary Tract Disease (FLUTD) refers to a number of conditions affecting the bladder and urethra of cats. There are many causes of FLUTD including urolithiasis, urethral plugs, urinary tract infections (UTIs), anatomic defects and neoplasia. However, often the underlying cause is unclear, and these cases are termed idiopathic cystitis. Different names have been given to the condition including Feline Idiopathic Cystitis (FIC), Feline stress-induced cystitis and idiopathic FLUTD. It is widely accepted that stress is a common contributory factor in FLUTD, and this is especially true in the case of FIC.

What is FIC?

FIC or Feline idiopathic cystitis is a diagnosis of exclusion made once all known causes of the clinical signs have been ruled out. Young to middle-aged cats tend to be over-represented with males and females equally at risk.

Clinical signs of FIC

The main clinical signs of FIC are:

  • Dysuria (difficult or painful urination)
  • Haematuria (blood in the urine)
  • Pollakiuria (increased urinary frequency)
  • Overgrooming, especially around the perineum
  • Stranguria (straining to urinate due to a blockage)

Clinical signs, such as haematuria in cats are not unique to FIC. Indeed, signs of UTI in cats are very similar, as are those for other causes of FLUTD too.

Pathogenesis of FIC

Extensive research has proposed a number of different hypotheses for the aetiology of FIC and in recent years, the role that stress has in triggering and exacerbating the condition has become widely acknowledged. Although it is a diagnosis of exclusion, many cats with other forms of FLUTD (such as feline urolithiasis, urethral spasm or urethral plugs) will also have FIC.

The pathogenesis of FIC is complex and multi-factorial and is likely to be more than just a ‘cat bladder’ disease. Indeed, it is thought to involve interactions between the nervous system, bladder and adrenal glands, as well as environmental and husbandry factors. Sources of feline stress exacerbate the condition.

A number of abnormalities are common in cats with FIC and are likely to contribute to disease pathogenesis:

  1. Neurogenic inflammation

Neurogenic inflammation is a form of inflammation initiated by activation of the peripheral nervous system C-fibres (pain fibres). C-fibres may be stimulated by central triggers in the brain, such as stress, or local triggers in the bladder, such as noxious compounds in urine. Stimulation of these C-fibres results in the release of neuropeptides including Substance P. Substance P causes:

  • Pain
  • Vasodilation
  • Oedema
  • Smooth muscle contraction
  • Increased vascular and bladder wall permeability
  • Mast cell degranulation results in the release of inflammatory mediators which further exacerbates the condition.

Bladder wall biopsies of cats affected by FIC tend to show higher numbers of C-fibres and Substance P receptors than unaffected cats.

  1. Feline bladder lining abnormalities and the role of GAGs

The bladder urothelium is not innately resistant to the corrosive effects of urine. However, a hydrophobic mucus layer rich in glycosaminoglycans (GAGs) and glycoproteins provides some protection. Damage to this GAG layer increases bladder wall permeability and allows noxious substances in the urine to pass through the urothelium causing inflammation as well as increasing activation of C-fibres. GAGs are also thought to decrease adherence of bacteria and crystals to the bladder lining.

  1. Stress

Chronic stress has the most influence on the pathogenesis of FIC and inter-cat conflict is top of the list of chronic stressors in the UK. Subtle signs of tension between cats can be easy to miss and careful history taking is needed.

  1. Abnormal stress response

Stress is widely accepted as being important in triggering FIC and there is also evidence that cats with FIC have an abnormal response to stress. Stress normally causes the release of catecholamines (adrenaline and noradrenaline) and cortisol, but whilst cats with FIC tend to have high levels of catecholamines, they have been shown to have smaller adrenal glands and subnormal cortisol production, leading to a reduced physiological ability to handle stressful situations.

Chronic activation of the central threat response system (CTRS) underlies this abnormal stress response, and it may be related to adverse early life experiences. For example, if a pregnant queen experiences trauma, it may sensitise the CTRS of the kittens and increase their stress susceptibility in the future.

Managing idiopathic cystitis in cats

The key to managing idiopathic cystitis in cats is a multimodal approach with a strong focus on stress reduction. Armed with an understanding of the pathogenesis of FIC, the following management tools should be considered:

  • · Adequate resources in multi-cat households

Litter trays are a common source of tension amongst cats in multi-cat households. With this in mind, there should be one litter tray per cat plus an extra one and these should be distributed around the house, a suitable distance apart to avoid conflict. Cats are quite solitary creatures, and each cat needs their own space to eat, drink and sleep too.

Used alongside these management practices, synthetic pheromone products can help reduce tension and inter-cat aggression in multi-cat households.

  • · Nutraceuticals to help relieve cat stress

Nutraceuticals that help to alleviate anxiety can be useful. L-tryptophan is an essential amino acid and a precursor for serotonin synthesis. Serotonin is a neurotransmitter that has a positive effect on mood and feelings of well-being and one study suggested that L-tryptophan supplements can decrease signs of anxiety.1

Alpha-casozepine is a milk protein hydrolysate that binds with the GABA-A receptor and one study showed a beneficial effect in reducing anxiety.2

  • · Encouraging the production of dilute urine

A feline urine specific gravity of 1.035 should be aimed to dilute irritant compounds in the bladder and help reduce bladder wall inflammation. Commonly advised techniques to increase water consumption, such as water fountains, wet diets and multiple water bowls should be employed together with the use of urinary diets that encourage water intake.

  • · GAG supplements

It has been suggested that GAG supplements may attach to the bladder wall and help reduce bladder wall permeability to irritant substances in urine, however, there is limited evidence of any beneficial effect.

So is cystitis in cats caused by stress? Stress is certainly central to the pathogenesis of FIC which in turn is the commonest cause of FLUTD. Stress reduction is imperative for the successful long-term management of cats with FLUTD and FIC.

References

  1. Pereira GG, Fragoso S and Pires E (2010). Effect of dietary intake of L-tryptophan supplementation on multihoused cats presenting stress-related behaviours, BSAVA
  2. Beata C, Beaumont-Graff E, Coll V et al (2007). Effect of alpha-casozepine (Zylkene) on anxiety in cats, J Vet Behav 2(2): 40-46.

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