Pathophysiology

3. Pathophysiology

Feline Idiopathic Cystitis

Feline idiopathic (or interstitial) cystitis (FIC) is thought to be a noninfectious, inflammatory, psychoneuroendocrine disorder with abnormalities in the bladder, central nervous system and hypothalamic-pituitary-adrenal response system (Figure 7). It is hypothesized that decreased levels of glycosaminoglycans (GAG) reduce the protective effect of the uroepithelium permitting urine constituents such as calcium and potassium ions to penetrate the epithelium and cause inflammation (Buffington et al., 1994; 1999a; Buffington & Pacak, 2001; 2002; 2004; Westropp et al., 2002; 2003; Pereira et al., 2004). In addition, the ions may stimulate the sensory neurons (C-fibers) in the submucosa, which, via the spinal cord and brain, are perceived as pain. Stressors in a sensitive cat’s environment may precipitate clinical signs by activation of the efferent sympathetic nervous system, which stimulates the dorsal root ganglia. The dorsal root ganglia cause the peripheral release of neuropeptides and mediators responsible for inflammation and pain (Buffington et al., 1994; 1999a; Buffington & Pacak, 2001; 2002; 2004; Westropp et al., 2002; 2003; Pereira et al., 2004)).

Significantly more owners of cats with FIC than owners of healthy cats or cats with other diseases perceived that their cats had fear, nervousness, and aggression supporting the theory that affected cats have an underlying stress disorder (Buffington et al., 2006a, 2006b). (© Yves Lanceau/Royal Canin (Singapura)).

Cats may be born with a predisposition to FIC and clinical signs of FLUTD are manifested if such a cat is placed in a "provocative or stressful" environment. FIC is a chronic, waxing and waning disease characterized by periods of remission interspersed with relapse precipitated by stress. Some affected cats have been shown to have small adrenal glands (Westropp et al., 2003).

Figure 7. Schematic representation of the proposed pathophysiological alterations in cats with feline idiopathic/interstitial cystitis. (Adapted from Buffington et al., 1999a).

Urethral Plugs

Urethral plugs are disorganized precipitates typically composed of sloughed tissues, blood or inflammatory cells, mixed with large quantities of matrix. Crystalline material may or may not be present. Struvite is the predominate mineral type in those urethral plugs that contain a mineral component. There are physical differences and probably etiological differences between uroliths and urethral plugs however, the actual cause of the matrix-crystalline plugs has not been clearly determined. It has been suggested, but not definitively established that Tamm-Horsfall mucoprotein is the predominant matrix compound which has been hypothesized to be a local host defense mechanism. (Kruger et al., 1991; Osborne et al., 1992b;1996c; 1996d; Houston et al., 2003; Forrester, 2006). Urethral plugs are much more common in male cats and cause partial or complete urinary tract obstruction. FIC may predispose some cats to forming urethral plugs.

Uroliths

A urolith (commonly referred to as a stone) is defined as the formation of sediment, consisting of one or more poorly soluble crystalloids, in the urinary tract. Microscopic sediment is referred to as crystals, and macroscopic precipitates are called uroliths.

Urinary crystals form when the urine is supersaturated with respect to a specific mineral or mineral compound. Precipitation is a result of increasing supersaturation. The initial phase, or nucleation, of urolith formation involves the formation of a crystal nidus. This phase is dependent on supersaturation of urine with calculogenic crystalloids and is influenced by the extent of renal excretion of the crystalloid, the urine pH, urine temperature, the presence or absence of various inhibitory factors (e.g., citrate, pyrophosphate), and the presence of promoters of crystallization (e.g., dead cells, cellular debris, protein, bacteria or other crystals). Crystal growth depends on the ability of the nidus to remain within the urinary tract, the duration of supersaturation of the urine and the physical ultra structure of the crystal. The actual rate of growth of the urolith depends on numerous factors including mineral composition and risk factors such as infection (Osborne et al., 1996a,b; 2000).