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Peer reviewed


Current Thoughts on
Pathophysiology & Treatment of


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; approximately⅔2/3 of
cats with FLUTD have FIC.
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 categories—based
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.


Today’s Veterinary Practice November/December 2013

Feline Idiopathic Cystitis
When the cause of cystitis—inflammation of the bladder—in 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
2. It captures the dismay and dispute associated with
the identification of many problems beyond the bladder/urethra.
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
• Increased bladder wall permeability: Most likely
caused by a combination of damage to, and dysfunction of, the uroepithelial cells and overlaying glycosaminoglycan layer

• Urethral obstruction in male cats. which indicates the potential for reduced adrenocortical reserve. tumors. or cold/rainy weather. availability. superimposed on increased corticotropin-releasing factor and adrenocorticotropic hormone concentrations. or illness • Possible role of viruses (eg. COmPARING CySTITIS IN WOmEN & CATS There are numerous similarities between cats with idiopathic cystitis and women with interstitial cystitis (cause unknown in women). easily expressed bladder • Thickened bladder walls • Pain in the bladder region upon abdominal palpation • Microscopic or gross hematuria (if not observed. if urine is obtained by any other method. should be performed in cats with: • recurrent cystitis • Underlying medical conditions • Urethral catheters that have been recently removed. similarities include: • chronic irritative voiding patterns • sterile urine • Prominent bladder mucosal vascularity. feline caliciviruses) • Increased uroepithelial permeability: Allows irritating protons and potassium ions from concentrated urine to penetrate the submucosa and stimulate sensory neurons. and space.PaThoPhysiology & TreaTmenT of feline idioPaThic cysTiTis | Table. guria. Physical Examination An unobstructed cat with FIC typically appears healthy. house sitters. Diagnostics Diagnosis of FIC is one of exclusion—no anatomic abnormalities are present and urine culture is negative. • Additional stressors in multiple cat households may include intercat aggression due to competition for access to water. urolithiasis). osteoarthritis. a new pet or baby in the home. approximately 50% of cats that experience an acute episode of FIC have a recurrent episode within 1 year. cystocentesis is the ideal way to obtain urine for bacterial culture. traveling. urachal remnants. with sediment examination and urine culture and sensitivity. November/December 2013 Today’s Veterinary Practice 39 . food. • Decreased urine volume and frequency of urination complicate FIC due to highly concentrated urine and increased urine/uroepithelial contact time. and cats appear to be a good model for this disease in humans. • Radiography or ultrasonography rules out anatomic abnormalities (eg. which is a potential complication of FIC. litter boxes. however. CLINICAL FEATURES & DIAGNOSIS Clinical signs of FIC depend on the component of the disease complex present: • Acute episodes of cystitis (pollakiuria. consider behavioral causes of abnormal urination). Potential causes: decreased Urine Volume & Urination frequency • castration (male cats) • confinement • decreased physical activity (eg. polyps. osteoarthritis) • decreased water consumption due to water taste. hematuria. a quantitative urine culture should be performed due to the potential for urine contamination. • 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.8 • Increased uroepithelial paracellular permeability may also be related to decreased cortisol concentrations because cortisol enhances cellular tight junction integrity in many tissues. due to cold weather. The Table lists potential causes for these decreases. but may have: • A small. • Decreased cortisol concentrations subsequent to ACTH stimulation have been observed. Role of Stress Stress is often implicated in FIC even though its role is difficult to prove: • History frequently points to a recent association with boarding. periuria) resolve with or without treatment within 7 days. 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. or temperature • dirty or poorly available litter boxes • intercat aggression • obesity. 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. dysuria. strantvpjournal. • Multiple recurrent episodes (up to 15%) or persistent forms of cystitis (up to 15%) occur in some KEy POINTS OF URINALySIS Urinalysis.

005–0. • Should be individualized to each cat. the urine culture is positive. cystoscopic abnormalities persisted. pheromone therapy) have been recommended for the treatment of FIC. owners reported fewer clinical signs in cats treated with amitriptyline.01-0. TREATmENT Treatment for idiopathic cystitis is dependent on clinical signs at presentation. Increased contact between owners and affected cats may also reduce stress.9 It should be noted. more than 70% of cats with fic appeared to respond to placebo treatments (eg. Toys that periodically release food may also help stimulate hunting activities. Because fic signs tend to wax and wane.5 mg/kg Q 4–8 H Numerous agents. and bacterial contamination has been ruled out.2–0. tranquilizers. that despite owner-reported improvement in clinical signs. These diagnostics should be employed in all cases of recurrent cystitis. grooming. nonsteroidal antiinflammatory drugs. the practitioner should try to identify an underlying cause of the urinary tract .| PaThoPhysiology & TreaTmenT of feline idioPaThic cysTiTis • Urinalysis. such as chasing laser pointer light dots and feathered or tailed toys. rules out bacterial urinary tract infections. size. this resolution was linked to the antibiotic therapy. treatment results. apparently positive. both therapies would achieve the same. the cat does not have FIC and should be treated with antibiotics. if clinical signs do not resolve in 3 to 5 days of therapy. type of litter. and regular versus self-cleaning aspects of litter boxes may affect acceptance and usage. and anti-inflammatory drugs (eg. • In addition. clinical signs resolve within 2 to 3 days. feeding canned cat food. amitriptyline. Access to several sources of fresh food and water may also help decrease stress as well as increase water intake. The waxing/waning nature of clinical signs associated with fic continue to complicate the evaluation of potential treatments. the clinical signs would abate but. including antibiotics. dimethylsulfoxide. urinalysis. • Litter boxes should be cleaned frequently and placed in convenient locations. shape. Because cats with FIC typically have sterile urine. in cats with recurrent episodes. Therefore. 40 Today’s Veterinary Practice November/December 2013 mANAGEmENT OF ACUTE Versus RECURRENT CySTITIS in a large majority of cats with fic. Litter box hygiene may be one of the most important aspects of MEMO. diagnostics (eg. lactose. it is debatable whether diagnostic workups need to be performed in young cats with first-time presentations. anticholinergics. tvpjournal. glucocorticoids. and if they were to be treated with antibiotics or placebo. and playing games that simulate hunting behavior. THE CHALLENGES OF TREATmENT for many years. ideally via cystocentesis (see Key Points of Urinalysis). The primary treatment objectives in cats with acute presentations are to: • Reduce stress and sympathetic output • Provide pain relief. cats with lower urinary tract signs due to fic were treated with antibiotics. imaging. further diagnostics and treatment are indicated. with sediment examination and culture and sensitivity. wheat flour). In 1 noncontrolled study of cats with severe recurrent idiopathic cystitis. In addition. on the other hand. Cats with acute onset of lower urinary tract clinical signs will often become asymptomatic within 5 to 7 days. Environmental modification The stress of some indoor environments may contribute to development and maintenance of clinical signs associated with FIC. they do not require antibiotic therapy. no controlled studies have demonstrated the efficacy of any of these agents. however. open versus hooded. suggesting the possibility of placebo effect. antispasmodics. medical Therapy Analgesic therapy can be provided by: • Buprenorphine: » IV or IM: 0.02 mg/kg Q 12 H • Butorphanol: » IV or SC: 0.4 mg/kg Q 2-6 H » PO: 1. 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. the number.01 mg/kg Q 4–8 H » Transmucosal (buccal): 0. Increased access to private spaces may also be beneficial for cats. Examples of stress-reducing human/cat contact include petting. in the minds of the practitioner and cat owner. it is important to remember that more than 95% of young cats with lower urinary tract clinical signs have sterile urine. If pyuria or bacteriuria is observed in the urine sediment. whether treatment is instituted or not (see The Challenges of Treatment). in controlled studies. glycosaminoglycans. cystoscopy) are indicated. Treatment for acute episodes of fic should include analgesics and. However. especially those living in multiple-pet households. urine culture.

7. Feldman eC (eds): Textbook of Veterinary Internal Medicine. Kendall Ms. 25:784-796. Kendall Ms. st louis: elsevier/saunders. JAVMA 1998. JAVMA 2011. Chew dJ. in Bartges J. pp 745-754. J Vet Intern Med 2011. Grauer has also served as President and Chairman of the Board of Regents of the American College of Veterinary Internal Medicine. west sussex. 2000. idiopathic lower urinary tract disease in cats. 2. Kruger JM. incidence rates of feline lower urinary tract disease in the United states. Proc ACVIM Forum. 3. Less concentrated urine is likely less irritating. flUTd = feline lower urinary tract disease. 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. westropp Jl. 213:1282-1286. Chew dJ. Buffington CaT. These benefits of a canned diet are often associated with improvement of clinical signs of FIC. Clinical evaluation of cats with nonobstructive urinary tract diseases. 170:24922497. osborne Ca. Gloucester. p 264. lawler dF. 199:211-216. Buffington CaT. pp 1828-1850. osborne Ca. Feline lower urinary tract diseases. Suggested Reading Buffington CaT. in elliott Ja. et al. JAVMA 1997. Feline idiopathic cystitis. MS. JAVMA 1991. et al. the change in food texture and increased human/cat contact associated with feeding a canned cat food may also decrease stress and sympathetic output. Buffington CaT. Chew dJ. et al. 4. epidemiologic study of risk factors for lower urinary tract diseases in cats. Management of non-obstructive idiopathic/interstitial cystitis in cats. Buffington CaT. et al. JAVMA 2001. 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. 6. Diplomate. idiopathic cystitis in domestic cats–beyond the lower urinary tract. 210:46-50. DVM. Philadelphia: wB saunders. Chew dJ. welk Ka. Kruger JM. Merrills J. JAVMA 2003. tvpjournal. amitriptyline treatment for severe recurrent idiopathic cystitis in cats. a yearlong prospective. UK: wiley-Blackwell. et al. stell Jl. Kruger J. especially if uroepithelial permeability is increased. 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. lord lK. Kruger JM. 222:749-758. Buffington November/December 2013 Today’s Veterinary Practice 41 . Philadelphia: wB saunders. Goyal sM. 11. He received his DVM from Iowa State University and completed postgraduate work at Colorado State University. 15:12-16. Dr. lulich JP. Grauer GF (eds): BSAVA Manual of Canine and Feline Nephrology and Urology. 8. 2005. Kaneene JB. 9. Polzin dJ (eds): Nephrology and Urology of Small Animals. UK: British small animal veterinary association.feline idioPaThic cysTiTis | Nutrition In cats that will accept the change. Conway Ts. Kansas State University. Grauer. randomized controlled trial of the efficacy of short-term amitriptyline administration for treatment of acute. Clinical evaluation of multimodal environmental modification (MeMo) in the management of cats with idiopathic cystitis. westropp Jl. 2007. randomized. Gregory F. 238:67-73. pp 894-896. Chew dJ. Feline Pract 1985. J Urol 2003. nonobstructive. 10. Clinical evaluation of cats with lower urinary tract disease. et al. 2011. small adrenal glands in cats with feline interstitial cystitis. sickness behaviors in response to unusual external events in healthy cats and cats with feline interstitial cystitis. 2nd ed. In addition. switching from a dry diet to a canned diet helps: • Increase water intake • Decrease urine concentration. doublemasked study of nutrition on feline idiopathic cystitis. memo = multimodal environmental modification References 1. J Fel Med Surg 2006. pp 888-893. westropp Jl. CvT update: idiopathic (interstitial) cystitis in cats. lekcharoensuk C. Buffington Ca. in ettinger sJ. westropp Jl. 218:1429-1435. 5. Buffington CaT. osborne Ca. June 2013. 6th ed. 8:261-268. Chew dJ. Buffington CaT. 2000. in Bonagura Jd (ed): Current Veterinary Therapy XIII. in Bonagura Jd (ed): Current Veterinary Therapy XIII. lulich JP. Recently. lulich J. nonobstructive idiopathic feline lower urinary tract disease: Therapeutic rights and wrongs.11 n fic = feline idiopathic cystitis.