Peer reviewed

Feline
Friendly
Article

Current Thoughts on
Pathophysiology & Treatment of

Feline
idioPaThiC
CysTiTis

Gregory F. Grauer, DVM, MS, Diplomate, ACVIM

(Small Animal Internal Medicine)

eline lower urinary tract disease (FLUTD) describes

a collection of conditions that can affect the bladder
and urethra of cats. Feline idiopathic cystitis (FIC) is
the most common form of FLUTD; approximately2/3 of
cats with FLUTD have FIC.
OVERVIEW
Prevalence & Risk Factors
FLUTD is responsible for 7% to 8% of all feline admissions to veterinary hospitals, and has been reported
in 0.49% to 1.26% of all cats.1,2
FLUTD appears to be equally prevalent in male and
female cats.
Both overweight cats and indoor cats are considered to be at greater risk for development of FLUTD;
however, urinary habits of outdoor cats may not be
observed as thoroughly.
Most FLUTD first occurs in cats between 2 and 6
years of age.3
Approximately 50% of cats that experience 1 episode
of FLUTD will have a recurrence.4
Common Causes
FLUTD can be divided into 2 broad categoriesbased
on presence or absence of an identifiable cause. Common causes of FLUTD, or conditions with clinical signs
that mimic the disease, include:
Anatomic abnormalities (eg, urachal remnants,
urethral strictures)
Behavioral abnormalities
Irritant cystitis, urinary tract infection, or uroliths
Neoplasia
Neurologic disorders
Trauma.

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Feline Idiopathic Cystitis

When the cause of cystitisinflammation of the bladderin cats remains unknown despite thorough diagnostic evaluation, it is referred to as feline idiopathic
cystitis (FIC). In large retrospective studies of cats with
FLUTD conducted at University of Minnesota and Ohio
State University, FIC was the most common diagnosis
(54% and 79% of cats, respectively).5,6
It was recently suggested that FIC is part of a larger
disorder that could be termed Pandora syndrome. The
name Pandora has been proposed for 2 reasons:7
1. The syndrome does not identify any specific cause or
organ
2. It captures the dismay and dispute associated with
the identification of many problems beyond the bladder/urethra.
PATHOGENESIS
FIC appears to be associated with complex interactions
among the nervous system, adrenal glands, and urinary bladder. Environment also appears to play a role
in the pathophysiology and, in some cases, FIC is associated with clinical signs related to the gastrointestinal, cardiovascular, respiratory, nervous, integumentary, and immune systems. These signs tend to wax and
wane, similar to urinary signs associated with cystitis.
Urinary System
Features of FIC directly related to the urinary system
include:
Increased bladder wall permeability: Most likely
caused by a combination of damage to, and dysfunction of, the uroepithelial cells and overlaying glycosaminoglycan layer
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Table. Potential causes: decreased Urine

Volume & Urination frequency
castration (male cats)
connement
decreased physical activity (eg, due to cold
weather, osteoarthritis)
decreased water consumption due to water
taste, availability, or temperature
dirty or poorly available litter boxes
intercat aggression
obesity, osteoarthritis, or illness
Possible role of viruses (eg, feline caliciviruses)

Increased uroepithelial permeability: Allows irritating

protons and potassium ions from concentrated urine to
penetrate the submucosa and stimulate sensory neurons.
Decreased urine volume and frequency of urination
complicate FIC due to highly concentrated urine and
increased urine/uroepithelial contact time. The Table
lists potential causes for these decreases.
Beyond the Urinary System
Pathophysiology of FIC is thought to extend beyond the
urinary bladder:
Increased tyrosine hydrolase within the brain is associated with increased sympathetic nervous system outflow.
Increased plasma concentrations of noradrenaline
have been documented and may:
Increase uroepithelial permeability
Increase nociceptive nerve fiber (C-fiber) activity
Activate local neurogenic bladder inflammatory
responses.
Decreased cortisol concentrations subsequent to
ACTH stimulation have been observed, superimposed
on increased corticotropin-releasing factor and adrenocorticotropic hormone concentrations, which indicates
the potential for reduced adrenocortical reserve.8
Increased uroepithelial paracellular permeability
may also be related to decreased cortisol concentrations
because cortisol enhances cellular tight junction integrity in many tissues.
Role of Stress
Stress is often implicated in FIC even though its role is
difcult to prove:
History frequently points to a recent association with
boarding, traveling, a new pet or baby in the home,
house sitters, or cold/rainy weather.
Additional stressors in multiple cat households may
include intercat aggression due to competition for
access to water, food, litter boxes, and space.
CLINICAL FEATURES & DIAGNOSIS
Clinical signs of FIC depend on the component of the disease complex present:
Acute episodes of cystitis (pollakiuria, dysuria, strantvpjournal.com

KEy POINTS OF URINALySIS

Urinalysis, with sediment examination and urine
culture and sensitivity, should be performed in cats
with:
recurrent cystitis
Underlying medical conditions
Urethral catheters that have been recently
removed.
cystocentesis is the ideal way to obtain urine for
bacterial culture; if urine is obtained by any other
method, a quantitative urine culture should be performed due to the potential for urine contamination.

guria, hematuria, periuria) resolve with or without treatment within 7 days; however, approximately 50% of cats
that experience an acute episode of FIC have a recurrent
episode within 1 year.
Multiple recurrent episodes (up to 15%) or persistent
forms of cystitis (up to 15%) occur in some cats.
Urethral obstruction in male cats, which is a potential
complication of FIC.
Physical Examination
An unobstructed cat with FIC typically appears healthy,
but may have:
A small, easily expressed bladder
Thickened bladder walls
Pain in the bladder region upon abdominal palpation
Microscopic or gross hematuria (if not observed, consider behavioral causes of abnormal urination).
Diagnostics
Diagnosis of FIC is one of exclusionno anatomic abnormalities are present and urine culture is negative.
Radiography or ultrasonography rules out anatomic
abnormalities (eg, urachal remnants, polyps, tumors,
urolithiasis).

COmPARING CySTITIS IN WOmEN & CATS

There are numerous similarities between cats with
idiopathic cystitis and women with interstitial cystitis (cause unknown in women), and cats appear to
be a good model for this disease in humans. similarities include:
chronic irritative voiding patterns
sterile urine
Prominent bladder mucosal vascularity, with
spontaneous mucosal hemorrhages observed
during cystoscopy
decreased mucosal production of glycosaminoglycan
increased numbers of mast cells and sensory afferent neurons in bladder mucosal biopsy samples.

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| PaThoPhysiology & TreaTmenT of feline idioPaThic cysTiTis

Urinalysis, with sediment examination and culture

and sensitivity, ideally via cystocentesis (see Key
Points of Urinalysis), rules out bacterial urinary
tract infections.
These diagnostics should be employed in all cases of
recurrent cystitis.
Because cats with FIC typically have sterile urine, they
do not require antibiotic therapy. If pyuria or bacteriuria
is observed in the urine sediment, the urine culture is
positive, and bacterial contamination has been ruled out,
the cat does not have FIC and should be treated with antibiotics. In addition, the practitioner should try to identify an underlying cause of the urinary tract infection.
TREATmENT
Treatment for idiopathic cystitis is dependent on clinical signs at presentation. Cats with acute onset of lower
urinary tract clinical signs will often become asymptomatic within 5 to 7 days, whether treatment is instituted or not (see The Challenges of Treatment).
The primary treatment objectives in cats with acute
presentations are to:
Reduce stress and sympathetic output
Provide pain relief.
medical Therapy
Analgesic therapy can be provided by:
Buprenorphine:
IV or IM: 0.0050.01 mg/kg Q 48 H
Transmucosal (buccal): 0.01-0.02 mg/kg Q 12 H
Butorphanol:
IV or SC: 0.20.4 mg/kg Q 2-6 H
PO: 1.5 mg/kg Q 48 H
Numerous agents, including antibiotics, tranquilizers, anticholinergics, antispasmodics, glycosaminoglycans, amitriptyline, and anti-inflammatory drugs (eg,

THE CHALLENGES OF TREATmENT

for many years, cats with lower urinary tract
signs due to fic were treated with antibiotics.
Because fic signs tend to wax and wane, the
clinical signs would abate but, in the minds of the
practitioner and cat owner, this resolution was
linked to the antibiotic therapy.
it is important to remember that more than
95% of young cats with lower urinary tract clinical
signs have sterile urine, and if they were to be
treated with antibiotics or placebo, both therapies
would achieve the same, apparently positive,
treatment results.
The waxing/waning nature of clinical signs
associated with fic continue to complicate the
evaluation of potential treatments. in controlled
studies, more than 70% of cats with fic
appeared to respond to placebo treatments (eg,
lactose, wheat our).

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Todays Veterinary Practice November/December 2013

mANAGEmENT OF ACUTE Versus

RECURRENT CySTITIS
in a large majority of cats with fic, clinical signs
resolve within 2 to 3 days. Therefore, it is debatable whether diagnostic workups need to be performed in young cats with first-time presentations. on the other hand, in cats with recurrent
episodes, diagnostics (eg, imaging, urinalysis,
urine culture, cystoscopy) are indicated. Treatment for acute episodes of fic should include
analgesics and, if clinical signs do not resolve in
3 to 5 days of therapy, further diagnostics and
treatment are indicated.

dimethylsulfoxide, glucocorticoids, nonsteroidal antiinammatory drugs, pheromone therapy) have been

recommended for the treatment of FIC. However, no
controlled studies have demonstrated the efcacy of any
of these agents.
In 1 noncontrolled study of cats with severe recurrent
idiopathic cystitis, owners reported fewer clinical signs
in cats treated with amitriptyline.9 It should be noted,
however, that despite owner-reported improvement in
clinical signs, cystoscopic abnormalities persisted, suggesting the possibility of placebo effect.
Environmental modification
The stress of some indoor environments may contribute
to development and maintenance of clinical signs associated with FIC. Multimodal environmental modification
(MEMO):10
Has been shown to be an effective management tool for
FIC
Is believed to reduce the number and severity of
recurrent episodes.
Should be individualized to each cat.
Litter box hygiene may be one of the most important
aspects of MEMO.
Litter boxes should be cleaned frequently and placed
in convenient locations.
In addition, the number, size, shape, type of litter,
open versus hooded, and regular versus self-cleaning aspects of litter boxes may affect acceptance and
usage.
Access to several sources of fresh food and water
may also help decrease stress as well as increase water
intake.
Increased contact between owners and affected
cats may also reduce stress. Examples of stress-reducing human/cat contact include petting, grooming, feeding canned cat food, and playing games that simulate
hunting behavior, such as chasing laser pointer light
dots and feathered or tailed toys. Toys that periodically
release food may also help stimulate hunting activities.
Increased access to private spaces may also be beneficial for cats, especially those living in multiple-pet
households.
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Nutrition
In cats that will accept the change,
switching from a dry diet to a
canned diet helps:
Increase water intake
Decrease urine concentration.
These benefits of a canned diet
are often associated with improvement of clinical signs of FIC. Less
concentrated urine is likely less irritating, especially if uroepithelial
permeability is increased. In addition, the change in food texture and
increased human/cat contact associated with feeding a canned cat food
may also decrease stress and sympathetic output.
Recently, a dietary trial assessing
the effects of antioxidant and fatty
acid supplementation in both canned
and dry cat foods demonstrated that
such foods were associated with
decreased number and severity of
recurrent episodes.11 n
fic = feline idiopathic cystitis;
flUTd = feline lower urinary tract
disease; memo = multimodal
environmental modification
References
1. lawler dF. incidence rates of feline lower
urinary tract disease in the United states.
Feline Pract 1985; 15:12-16.
2. lekcharoensuk C, osborne Ca, lulich
JP. epidemiologic study of risk factors for
lower urinary tract diseases in cats. JAVMA
2001; 218:1429-1435.
3. Buffington CaT, Chew dJ. Management
of non-obstructive idiopathic/interstitial
cystitis in cats. in elliott Ja, Grauer GF
(eds): BSAVA Manual of Canine and
Feline Nephrology and Urology, 2nd ed.
Gloucester, UK: British small animal
veterinary association, 2007, p 264.
4. westropp Jl. Feline idiopathic cystitis. in
Bartges J, Polzin dJ (eds): Nephrology and
Urology of Small Animals. west sussex,
UK: wiley-Blackwell, 2011, pp 745-754.

5.

Kruger JM, osborne Ca, Goyal sM, et

al. Clinical evaluation of cats with lower
urinary tract disease. JAVMA 1991;
199:211-216.
6. Buffington CaT, Chew dJ, Kendall Ms,
et al. Clinical evaluation of cats with
nonobstructive urinary tract diseases.
JAVMA 1997; 210:46-50.
7. Bufngton CaT. idiopathic cystitis in
domestic catsbeyond the lower urinary
tract. J Vet Intern Med 2011; 25:784-796.
8. westropp Jl, welk Ka, Buffington CaT.
small adrenal glands in cats with feline
interstitial cystitis. J Urol 2003; 170:24922497.
9. Chew dJ, Buffington CaT, Kendall Ms,
et al. amitriptyline treatment for severe
recurrent idiopathic cystitis in cats. JAVMA
1998; 213:1282-1286.
10. Buffington Ca, westropp Jl, Chew dJ,
et al. Clinical evaluation of multimodal
environmental modification (MeMo) in
the management of cats with idiopathic
cystitis. J Fel Med Surg 2006; 8:261-268.
11. Kruger J, lulich J, Merrills J, et al. a yearlong prospective, randomized, doublemasked study of nutrition on feline
idiopathic cystitis. Proc ACVIM Forum,
June 2013.
Suggested Reading
Bufngton CaT, Chew dJ. CvT update:
idiopathic (interstitial) cystitis in cats. in
Bonagura Jd (ed): Current Veterinary
Therapy XIII. Philadelphia: wB saunders,
2000, pp 894-896.
Kruger JM, osborne Ca, lulich JP.
nonobstructive idiopathic feline lower
urinary tract disease: Therapeutic rights
and wrongs. in Bonagura Jd (ed): Current
Veterinary Therapy XIII. Philadelphia: wB
saunders, 2000, pp 888-893.
Kruger JM, Conway Ts, Kaneene JB, et al.
randomized controlled trial of the efficacy
of short-term amitriptyline administration
for treatment of acute, nonobstructive,
idiopathic lower urinary tract disease in
cats. JAVMA 2003; 222:749-758.
stell Jl, lord lK, Buffington Ca. sickness
behaviors in response to unusual external
events in healthy cats and cats with feline
interstitial cystitis. JAVMA 2011; 238:67-73.
westropp Jl, Buffington CaT, Chew dJ. Feline
lower urinary tract diseases. in ettinger sJ,
Feldman eC (eds): Textbook of Veterinary
Internal Medicine, 6th ed. st louis:
elsevier/saunders, 2005, pp 1828-1850.

Gregory F. Grauer, DVM, MS, Diplomate,

ACVIM (Small Animal Internal Medicine) is a
professor and the Jarvis Chair of Small Animal
Internal Medicine in the Department of Clinical Sciences at the College of Veterinary Medicine, Kansas State University. His clinical and
research interests involve the small animal urinary system and he recently co-edited the
BsaVa manual of canine and feline nephrology and Urology. Dr. Grauer has also served as President and Chairman of the Board of Regents of the American College of Veterinary
Internal Medicine. He received his DVM from Iowa State University
and completed postgraduate work at Colorado State University.

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