Asociación Mexicana de Médicos Veterinarios Especialistas en Pequeñas Especies

Transcription

1 Asociación Mexicana de Médicos Veterinarios Especialistas en Pequeñas Especies XXXI CONGRESO NACIONAL DE LA ASOCIACIÓN MEXICANA DE MÉDICOS VETERINARIOS ESPECIALISTAS EN PEQUEÑAS ESPECIES, A.C. DRA. IRENE JOYCE BLANK Mayo 23 al 25 de 2013 FELINE BLADDER DISEASE Dr. John R. August Texas A&M University Introduction Irritative voiding (frequent attempts to urinate, often with hematuria) is a common problem in cats. The causes of these clinical signs differ between cats and dogs, especially when the problem affects young adult cats. The most important cause for this difference is the occurrence of feline idiopathic cystitis (FIC) a disease that does not occur in dogs.

2 Differential Diagnosis In spite of the frequent incidence of irritative voiding as a presenting complaint in practice, it would appear that the number of primary diseases that cause these clinical signs is quite small. Importantly, any of these diseases can cause inflammation and swelling of the mucosa of the lower urinary tract, and the formation of cellular, amorphous, and inorganic debris in the lumen. Inability to void these materials may lead to urethral obstruction in male cats, whatever the primary cause. The differential diagnosis of irritative voiding varies according to the age of the patient when presented. Sterile causes of irritative voiding are most common in young adult cats up to 5 years of age. As cats become middle-aged, their susceptibility to microbial infections increases, changing the differential diagnosis for this age cohort. Finally, senior cats, already susceptible to opportunistic colonization of the urinary tract, also are at risk for neoplasia. While it is convenient to think of cats as having 4 main etiopathogenetic causes of irritative voiding described below, and to direct diagnostic evaluation and client funds to identify the one inciting cause, it is important to remember that many chronically affected cats may have more than 1 disease contributing to the manifestation of clinical signs. Etiopathogenetic Causes Feline Interstitial Cystitis Feline interstitial cystitis (FIC) is the most common cause of irritative voiding in cats. FIC is a non-infectious inflammatory, painful lower urinary tract disease, and is diagnosed after tests to evaluate other causes of lower urinary tract irritation or inflammation have proved negative. Ideally, final confirmation of the diagnosis requires cystoscopic examination or bladder mucosal biopsy. Many of the recent advances made in our understanding of this complicated disease come from the research programs of Buffington, Westropp, Chew, and colleagues at The Ohio State University and The University of California, Davis. FIC is not simply a local bladder disease - affected cats have neuroendocrine abnormalities that contribute to the pathogenesis of the lesions, and they may be predisposed to related behavioral and gastrointestinal disorders. The complex pathophysiological mechanisms causing FIC are incompletely understood. Most likely, affected cats have prolonged and exaggerated autonomic responses to stress that initiate bladder inflammation, complicated by varying degrees of barrier dysfunction of the lining of the diseased bladder. Cats with FIC appear to have exaggerated and prolonged autonomic responses to stress and pain that initiate and perpetuate bladder inflammation. Affected cats have an uncoupling of their sympathetic nervous system from their hypothalamic-pituitary- adrenal (HPA) axis, as evidenced by elevated circulating catecholamines and rate- limiting brain enzymes. Abnormal sympathetic nervous system activity may cause the release of neurotransmitters or inflammatory mediators (such as Substance P) in the bladder, which promote

3 sensory nerve stimulation, mast cell degranulation, muscle contraction, and vascular leakage. Intravesical debris resulting from acute hemorrhage and vascular seepage may predispose male cats with FIC to urethral obstruction. Paradoxically, cats with FIC have smaller adrenal glands than unaffected cats and their response to ACTH stimulation is blunted, suggesting that they may have a mild form of primary hypoadrenocorticism. However, the predisposition to FIC is not ameliorated by the supplementation of affected cats with oral corticosteroids. Some human patients with IC have reduced glycosaminoglycans (GAG) excretion in their urine, and clinical improvement with oral GAG supplements is seen in 10 to 20% of affected persons. GAGs form a protective barrier on the surface of the urothelium, preventing penetration of underlying mucosal tissues by normal urine constituents. A defective or deficient GAG layer may increase the risk of a chemically-induced inflammation, especially if the urine is concentrated, acidic, or contains irritating substances, or if the mucosa and submucosa already are inflamed from stress-induced changes. Similar changes may be present in some cats with FIC. In addition, erosion of the urothelium may be present, further impairing barrier function. The permeability of the bladder mucosa of FIC patients is increased, especially when the bladder is distended. Histological changes include submucosal hemorrhages, increased numbers of mast cells, interstitial edema, and dilation of blood vessels. The submucosal hemorrhages, known as glomerulations in human medicine, are typical cystoscopic findings. The mucosal lesions are exacerbated by neurogenic inflammation Cystic Urolithiasis Most cats with small cystic uroliths are asymptomatic, although microscopic hematuria and crystalluria may be present on examination of sediment on routine urinalysis. Irritative voiding associated with uroliths occurs most commonly in middle-aged cats, although cats of any age may become affected. Uroliths form in cats most commonly because of complicated metabolic derangements, rather than from changes in urine composition associated with infection, as occurs in struvite urolithiasis in dogs. Although supersaturation of urine with the basic chemical components is an essential factor in the formation of most uroliths, other contributing factors participate in the process of stone development, including urine concentration and ph, urine retention, levels of promoters and inhibitors of crystal aggregation and growth, levels of noncrystalline matrix, intake of minerals in the diet and drinking water, and genetic factors. The incidence of calcium oxalate uroliths increased over the past two decades as pet- food manufacturers made adjustments to diets in response to the widespread problem of struvite urolithiasis in the feline population. Recent reports by stone analysis centers suggest that the proportion of stones submitted that are predominantly calcium oxalate may be decreasing slightly, again possibly in response to dietary modifications to address morbidity associated with calcium oxalate urolithiasis. Calcium oxalate uroliths are radio-opaque, non-dissolvable,

4 and are responsible almost exclusively for upper urinary tract urolithiasis. Although non-obstructing calcium oxalate or calcium phosphate nephroliths do not appear to accelerate decline in function in chronic kidney disease, obstructing ureteroliths are an important and common complication in cats with this disease. Ideally, all cats who have been diagnosed with chronic kidney disease should undergo careful abdominal imaging at first diagnosis to determine if upper (and lower) tract urolithiasis is present. Struvite (magnesium ammonium phosphate) uroliths occur most commonly as a metabolic disease in young and middle aged cats, with risk of development decreasing after 6 to 8 years of age. Bartges and colleagues at the University of Tennessee observed that infection-induced struvite calculi occur most commonly in cats less than 1 year of age and more than 10 years of age. Struvite calculi are very uncommon causes of upper tract urolithiasis, are usually radioopaque, and when metabolic in etiology are dissolvable with dissolution diets. Resolution of infection-induced stones requires complete eradication of the urease-producing bacterium responsible for altering urine ph, rather than dissolution. Purine uroliths are an uncommon cause of irritative voiding in cats. The bladder stones may be insufficiently radio-opaque to be detected on routine abdominal radiographs, requiring ultrasound examination or contrast cystography for diagnosis. The predisposition to formation of cystine uroliths may be associated with anatomical and/or cellular dysfunction of the liver, and affected cats should undergo careful abdominal imaging to exclude portovascular abnormalities and liver function tests. Dried-blood stones have been identified by Westropp and colleagues at the University of California, Davis, as an important cause of persistent hematuria in cats. The origin of the radiolucent stones is unclear, but they may result from chronic macroscopic hemorrhage due to some other bladder disease. Bacterial Cystitis Much of our recent knowledge about the role of bacteria in lower urinary tract disease comes from the work of Bartges and colleagues at the University of Tennessee and from Litster at Purdue University (see Take-Home Messages). Contrary to popular belief in practice, bacterial cystitis is an extremely uncommon cause of irritative voiding in young adult cats, most likely causing no more than 2% of cases in this age group. As a species, cats have retained some characteristics of their original desert heritage, including the production of small amounts of urine with high osmolality thereby inhibiting opportunistic bacterial growth. As cats age, however, they become susceptible to diseases that affect urine composition or concentration and neutrophil function. In association with these predisposing factors, age-related declines in surface immunity of the mucosa may increase the risk of successful bacterial colonization. Bacterial cystitis occurs most commonly in cats more than 10 years of age, and the most frequent predisposing cause is chronic kidney disease. Hyperthyroidism, diabetes mellitus, chronic corticosteroid treatment, retroviral

5 infections, and bladder neoplasia also are important predisposing diseases. Most infections occur from ascending colonization of the bladder with Escherichia coli, although enterococci and gram- negative rods may be involved occasionally. Not all affected cats are symptomatic; for example, it is estimated that bacteria can be cultured from the bladders of up to 20% of cats with chronic kidney disease at any given time. Most affected cats are infected with a single species of bacterium, and patients with proven bacterial cystitis should be evaluated very carefully to identify the underlying disease that is predisposing them to infection. Bladder Tumors Neoplasia of the bladder is an uncommon cause of irritative voiding in cats; however, its diagnostic significance increases when persistent hematuria and progressive dysuria or relapsing urinary tract infections develop in elderly cats, especially males who are predisposed to transitional cell carcinoma. Clinical signs are similar to those seen in cats with urinary tract infections and uroliths, although the degree of hematuria and tenesmus may be greater when neoplasia is present. Because cats with bladder neoplasia are predisposed to bacterial cystitis due to disruption of function and mucosal barriers, they are often treated for refractory bacterial infections repeatedly before the diagnosis of neoplasia is confirmed. This delay in diagnosis often allows tumor extension into the muscle layers of the bladder wall by the time the disease is detected. Often, a firm mass is palpated in the location of the bladder at first examination or after repeated unsuccessful attempts to eradicate bacterial infection. Metastasis occurs most commonly to the lungs, mesentery and parietal peritoneum, liver, and spleen. Take-Home Messages 1. FIC is a comorbid disease that is associated with several other conditions including separation anxiety syndrome. 2. FIC is a complicated neuroendocrine disorder primarily affecting the sympathetic nervous system and hypothalamic-pituitary-adrenal axis. 3. Abnormalities in fetal development may explain why some cats are predisposed to the disease. 4. An exaggerated and prolonged sympathetic response to environmental stressors occurs in sensitive cats. 5. Neurogenic stimulation may result in increased epithelial permeability, pain, vascular leakage, smooth muscle contraction, and histamine release. 6. Recurrence rate is high in the year following the first episode. 7. Bacterial infection is a very rare cause of cystitis in cats less than 5 years of age, but causes about 50% of cases in cats more than 10 years old. 8. Occult bacterial cystitis is an under-diagnosed problem, especially in older female cats. Patients with chronic kidney disease, diabetes mellitus, uncontrolled hyperthyroidism, or on long-term systemic corticosteroid therapy, should be monitored regularly. 9. Significant bacteriuria is defined as >1000 CFU/mL from a sample collected by cystocentesis. 10. The most common lower urinary pathogens are Escherichia coli, Enterococcus faecalis, and Staphylococcus felis. 11. In a urine sediment examination, rod bacteria can be identified when

6 >10,000 CFU/mL, and coccal organisms when >100,000/mL. 12. Hematuria with >5 WBCs/HPF, proteinuria, and an increased ph raise suspicion of overt or occult infection. 13. Uncomplicated infections (which are rare) should be treated for 10 to 14 days, and the urine cultured 7 days after treatment is completed. 14. While waiting on culture results, amoxicillin-clavulanic acid is an appropriate choice for gram-negative infections, and amoxicillin for grampositive infections. 15. A single injection of cefovocin clears uncomplicated urinary tract infections about 75% of the time. 16. Complicated infection should be treated for 4 to 6 weeks, with cultures being taken after 7 days, and then 7 days after treatment is completed. 17. In 2007, 49% of uroliths analyzed were struvite, compared to 41% calcium oxalate. 18. Calcium oxalate uroliths occur most commonly in older cats, 10 to 15 years old, and are responsible for almost all upper tract uroliths. 19. Sterile struvite uroliths occur most commonly in cats 1 to 10 years old. 20. Infection struvite uroliths occur most commonly in cats less than 1 year old and more than 10 years old. 21. Struvite is the most common inorganic ingredient found in urethral plugs. 22. By itself, struvite crystalluria is not pathogenic. 23. Tumors of the urinary bladder are rare in cats. It is important to first exclude other common causes of lower urinary tract signs. 24. Most cats with bladder tumors are diagnosed initially as having a urinary tract infection. Most of these cats have incomplete responses to antimicrobial treatment, or their infection recurs after discontinuation of therapy. 25. Transitional cell carcinoma (TCC) is the most common tumor of the urinary bladder in cats and occurs typically in older animals (usually >9 years of age). 26. Cats with urinary bladder tumors are presented with typical lower urinary tract signs 27. Demonstration of a bladder mass on ultrasound and a urine sediment revealing typical neoplastic cells are highly suggestive of TCC. Percutaneous tumor aspiration is not recommended for any bladder tumor. 28. The prognosis for cats with bladder tumors generally is poor; however, a combination of surgery and chemotherapy is most effective in controlling clinical signs.