Veterinary Medicine - February 2009 - (Page 85) POSSIBLE CAUSES It is important to understand the proposed causes of iFLUTD because they have led to a variety of therapies targeting those mechanisms. Many of the causes that have been suggested for iFLUTD have been extrapolated from research investigating interstitial cystitis in women. As more studies are conducted, further evidence for the cause or causes of iFLUTD may emerge, but based on the available body of knowledge, the disease appears to be multifactorial. Deļ¬cient glycosaminoglycan layer Glycosaminoglycans are a constituent of the mucin layer that protects the urothelium and prevents urine components from coming into direct contact with the bladder mucosa. One hypothesis suggests a de ciency of the glycosaminoglycan protective layer exposes the urothelium to these components, causing tissue damage and a leaky urothelium. Tissue injury exposes and stimulates pain-sensitive bers (C bers), causing the release of nucleus) that provide excitatory input in response to bladder distention have been shown to have higher activities of an enzyme, tyrosine hydroxylase, involved in catecholamine synthesis, and signi cantly higher plasma catecholamine concentrations have been documented in cats with iFLUTD compared with controls.20,21 Alpha2-adrenoreceptors, which normally inhibit catecholamine release and pain input to the brain, appear to be desensitized in cats with iFLUTD, possibly because of chronically Infection Bacterial cystitis leading to pain, inammation, and LUTS is one cause to consider. Most studies investigating the general causes of LUTS report a low overall incidence ( 10 years of age.6 However, a recent study evaluating cats in Norway with LUTS showed that 23% of cats with either obstructive or nonobstructive iFLUTD had positive culture results based on samples collected by either cystocentesis or midstream free-catch.7 Since most studies have been unable to demonstrate positive culture results in cats with iFLUTD, stealth organisms (those that are dif cult to identify through conventional diagnostic testing) have been implicated as causative agents of iFLUTD. Ureaplasma and Mycoplasma species have been associated with UTIs in several species, including people, rodents, sheep, dogs, and cats; because they have no cell wall, these organisms are dif cult to culture.8 However, in a recent study in which 91 urine samples from cats with recurrent iFLUTD and negative bacterial culture results were evaluated by using PCR assays to detect Mycoplasma and Ureaplasma species, the organisms were not identi ed.8 Viral particles such as bovine herpesvirus-4 and calicivirus have also been implicated.9,10 Recently, two novel feline caliciviruses were identi ed in two of 40 cats with iFLUTD,11 but their signi cance in iFLUTD is unknown. Bladder permeability and catecholamines decreased during enrichment. substance P (a neurotransmitter), mast cell activation and degranulation, inammation, and edema, which further affect the bladder urothelium, C bers, and afferent neurons.12,13 This cascade of events, known as neurogenic in ammation, may account for the vicious cycle of pain and dysuria. Histologic examination of bladder wall samples from cats with FIC reveals increased numbers of C bers, mast cells, and substance P receptors.13 In addition, low rates of glycosaminoglycan excretion and increased bladder wall permeability are present in both people and cats with interstitial cystitis.14-17 There is, however, some indication that abnormalities present in people with idiopathic cystitis, such as decreased glycosaminoglycans and increased mast cells, can be present in nonidiopathic cystitis disease, suggesting that these abnormalities are not a cause but a result of idiopathic cystitis.18,19 elevated catecholamine concentrations.22 Alpha2-adrenoreceptors are also found in the bladder and may play a role in blood ow.5 In these studies, cats were evaluated in both stressful and environmentally enriched conditions. Some of the parameters measured, such as catecholamine concentrations and bladder permeability, decreased during the enrichment phase. Other evidence that suggests these cats function abnormally under stress is smaller adrenal glands and a suboptimal response to synthetic ACTH in cats with iFLUTD compared with controls.23 SIGNALMENT, HISTORY, AND PHYSICAL EXAMINATION FINDINGS Cats with iFLUTD are typically between 4 and 7 years of age.6 No breed predisposition exists. Castrated males have an increased risk, while intact females have a decreased risk.6 Owners of cats with iFLUTD report one or more of the following signs: periuria, hematuria, pollakiuria, stranguria, or an inability to urinate.24 Cats may present in their rst episode or have a Stress Central nervous system involvement in the development of iFLUTD has been suggested in several studies. Areas in the brain (locus ceruleus, paraventricular VETERINARY MEDICINE February 2009 85
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