key: cord-0040511-umzmmtqd
authors: nan
title: Large Intestine
date: 2012-07-25
journal: Canine and Feline Gastroenterology
DOI: 10.1016/b978-1-4160-3661-6.00058-4
sha: 2c0f8ca20f0ed85b5ec4e2fceb5565782c425d27
doc_id: 40511
cord_uid: umzmmtqd

nan

Large Intestine

The large intestine of the dog and cat has evolved to serve two major functions: extraction of water and electrolytes from the fluid contents of the lumen and control of defecation. The large intestine accomplishes these functions by regulating fluid transport, bacterial fermentation, motility, immune surveillance, and blood flow. Sodium and water absorption serve to dehydrate the feces prior to defecation; mucus glycoproteins serve to trap bacterial pathogens and prevent bacterial translocation; epithelial cells, lymphocytes, plasma cells, macrophages, and dendritic cells serve to regulate the bacterial flora and the immune response to microbes; and motility serves to facilitate storage or defecation of feces. Perturbations in any of these functions may result in the problems of diarrhea, constipation, or systemic inflammatory response syndrome.

The large intestine consists of the cecum, colon, rectum, and anal canal (Figure 58-1). In dogs and cats, the ileum communicates directly with the colon, and what is referred to as the cecum in the dog and cat is actually a diverticulum of the proximal colon. The colon is further compartmentalized into ascending, transverse, and descending portions, each segment having slightly different functions and properties. The right colic or hepatic flexure separates the ascending and transverse colon, and the left colic or splenic flexure separates the transverse and descending colon. In dogs and cats, the large intestine contributes 20% to 25% of the total (small and large) intestinal length. 1, 2 The arterial blood supply to the colon is provided by the cranial and caudal mesenteric arteries, and venous return from the colon is transmitted to the main portal vein via the cranial and caudal mesenteric veins. Lymph is circulated from the colon to the right, middle, and left colic lymph nodes, and eventually into the cisterna chyli and thoracic duct. Parasympathetic innervation arises from the vagus nerve in the proximal colon, and from the pelvic nerves in the distal colon. Sympathetic innervation arises from the paravertebral ganglia and follows the lumbar splanchnic nerves and mesenteric arteries to the colonic mucosa and muscularis. Parasympathetic preganglionic fibers and sympathetic postganglionic fibers synapse on cell bodies and neurons of the enteric nervous system, respectively.

As with the small intestine, the cross-sectional structure of the large intestine consists of four distinct layers, that is, mucosa, submucosa, muscularis, and serosa ( Figure 58 -2). The large intestine differs from the small intestine in the following important ways: villi are absent in the large intestine; the microvilli of the large intestine epithelial cells are much less abundant; goblet cells are more prominent in the large intestine; endocrine cells are less prominent in the large intestine; and crypt-to-epithelial migration is a much slower process in the large intestine.

The mucosa of the large intestine is a flat absorptive surface area differing from the small intestine in that villi are not present. However, numerous straight tubular glands (400 to 600 µm) are present in parallel cylinders and they extend from the muscularis mucosa to the mucosal surface. 3 The glands are lined by a continuous sheet of columnar epithelial cells, which are separated from the mesenchymal tissue of the lamina propria by a well-defined basement membrane. The epithelium in the lower half of the crypts is composed of proliferating undifferentiated columnar cells, mucussecreting goblet cells, and at least three types of endocrine epithelial cells. 4 Cellular proliferation is predominantly in the lower part of the crypts in both dogs and cats. The epithelium of the upper half of the crypts consists of differentiating columnar cells, goblet cells, and a few endocrine cells. The flat absorptive surface is lined by many columnar cells as well as a moderate number of goblet cells (10 to 25 goblet cells per 100 epithelial cells), 3, 5 most of which are largely depleted of their mucous granules. Intraepithelial lymphocytes are relatively sparsely distributed throughout the epithelium (one to seven lymphocytes per 100 epithelial cells), 3, 5 and as in the small intestine, the predominant T cell subset is the cytotoxicsuppressor (CD8+) type. 6, 7 The cellular elements of the lamina propria of the large intestine resemble closely those found in the small intestine and include lymphocytes, many plasma cells, mast cells, macrophages, eosinophils, enteric neurons, and fibroblasts.

The innermost layer of the mucosa is separated from the submucosa by the muscularis mucosae, a layer of smooth muscle cells roughly eight to 10 cells (or 70 to 80 µm) thick. The submucosa of the colon resembles the submucosa of the other tubular digestive organs. It contains many blood and lymph vessels, dense connective tissue sparsely infiltrated by cells (fibroblasts, lymphocytes, plasma cells, mast cells, macrophages, and eosinophils), and the unmyelinated nerve fibers and ganglion cells that form the submucosal plexus.

The muscularis is composed of an inner circular muscular layer forming a tight spiral circumferentially along the course of the colon and an incomplete outer longitudinal muscle layer. The ganglion cells of the myenteric plexus of Auerbach are found between the circular and longitudinal muscle layers. Unmyelinated postganglionic fibers are also found in the circular muscle layer and communicate with the submucosal (Meissner) plexus. The interstitial cells of Cajal, which are located on the submucosal surface of the circular smooth muscle, play a dual role as pacemaker cells and as mediators of neuromuscular transmission in the colon. [8] [9] [10] The serosa is composed of mesothelial cells and covers only the portions of the large bowel that lay within the peritoneal cavity (cecum and colon).

Several classification systems for colonic mucosal architecture and cellularity have been proposed (see Chapter 29) . 1, 3, 11 It should be emphasized that there are important age, 12 site, 1,3 diet, [13] [14] [15] [16] and procedure-related 3 differences in the cellularity and architecture of the colonic mucosa, and these differences must be taken into account when interpreting colonic histology. For example, the protein and fiber content of the diet have significant effects on colonic mucosal morphology (e.g., crypt depth and cellularity). [14] [15] [16] The pathologist should always take these factors into account when interpreting colonic biopsy specimens. The method of biopsy also influences the architecture and cellularity of the mucosa. Compared to full-thickness biopsies, gland length is 25% to 30% shorter and goblet cell numbers are 70% to 75% less in endoscopic biopsies from the same animals. The shallow depth of the endoscopic biopsy apparently causes glandular collapse, and enema or cathartic preparative solutions are believed to cause discharge of mucous goblets. 3, 11 Function

A lubricant layer of mucus forms a crucial physiologic barrier between the colonic mucosa and the luminal environment. Mucus is a constantly changing mix of secretions and exfoliated epithelial cells, the chief determinants of which are high-molecular-weight glycoproteins or mucins. 17 Gastrointestinal mucins are secreted from goblet cells as they ascend from their origin in the crypts up to the colonic epithelium. Mucin secretion is dependent upon the close integration of the cystic fibrosis transmembrane regulator (CFTR), chloride secretion, and granule exocytosis. In addition to their physiologic role as a mucosal barrier, mucins may also have a pathologic role in the metastases of epithelial tumors and enhanced susceptibility to infection.

In health, approximately 2.7 L of fluid (oral intake, saliva, gastric fluid, bile, pancreatic fluid, and intestinal secretions) is presented each day to the small intestine of a 20-kg dog. Approximately 1.35 L reduced below 30 to 50 mEq/L, whereas net sodium absorption in the jejunum occurs only at luminal sodium concentrations above 130 mEq/L. 21 Chloride absorption in the colon has both passive and active properties. Passive chloride absorption primarily represents a potential-dependent process secondary to the electrical potential generated by electrogenic Na absorption.

Bicarbonate secretion is an important feature of colonic electrolyte function and helps to neutralize acids produced by bacterial fermentation. Chloride-bicarbonate (Cl-HCO 3 ) exchange is the primary cellular mechanism responsible for bicarbonate secretion.

The descending colon possesses both potassium absorptive and potassium secretory processes that are regulated by luminally and hormonally mediated mechanisms, and the overall net potassium movement represents the balance of these oppositely directed transport mechanisms. 20, 21 The colon, therefore, has the potential to serve as an important regulatory system for the maintenance of overall potassium balance. Although renal potassium transport is critical in the overall control of potassium balance, the colon also contributes to the maintenance of potassium balance by modifying both potassium secretion and absorption, especially when kidney function is impaired.

The colon contains a diverse array of immune cells, including T and B lymphocytes, plasma cells, macrophages, dendritic cells, antigenpresenting cells, mast cells, eosinophils, and neutrophils. 3, [5] [6] [7] [22] [23] [24] [25] Immune cells are found in the epithelium, lamina propria, and submucosa of the colon. As in the small intestine, appropriate interactions between these different cell types are essential in generating either immune responsiveness or tolerance to the large array of luminal antigens. 26, 27 Much less is known about colonic immunity, but some generalizations may be made. In the colon, CD8+ T cells are found primarily in the epithelium; very few CD8+ T cells are found in the lamina propria or submucosa. Most intraepithelial lymphocytes are CD3+/CD8+, a phenotype consistent with suppressor-cytotoxic functions. Lamina propria T cells on the other hand are predominantly of the CD4+ helper phenotype. Immunoglobulin (Ig) A-containing plasma cells are more prominent than IgG-or IgM-containing plasma cells in the lamina propria. Thus, in the normal colonic mucosa, a balance would appear to be maintained between helper and suppressor T-cell populations, which allows specific antigen responsiveness while avoiding hyperreactivity. 5, 6, 28 There are many similarities in the immune systems at both sites, but there are important differences in the immune response of the small and large intestine.

is absorbed in the jejunum, 1.0 L in the ileum, and 315 mL in the colon, leaving 35 mL in feces. 18 Thus, the jejunum absorbs 50%, the ileum 75%, and the colon 90% of fluid volume presented to it (Figure 58-3) . This fluid absorptive capacity of the colon is largely determined by basal electrolyte (primarily sodium) transport and by the ability of several agonists (aldosterone and glucocorticoids) to augment electrogenic and electroneutral Na absorption. As long as ileocecal flow is less than the colonic absorptive capacity, significant alterations in small intestinal fluid movement may be present, but colonic absorption will prevent the development of diarrhea. On the other hand, when small intestinal absorption and ileocecal flow are normal, a relatively small decrease in colonic absorption (inflammatory bowel disease) will produce significant increases in fecal water output.

The large intestine regulates the electrolyte and water composition of the feces. There are distinct differences in the mechanisms of electrolyte transport between the ascending and descending colon, 19, 20 but in general the canine and feline colon absorbs water, sodium, and chloride while secreting potassium and bicarbonate.

In many ways, the mechanisms of absorption and secretion in the large intestine are similar to those of the small intestine, but there are several important differences (Table 58-1) . Active nutrient (glucose, amino acid, monoglyceride) transport is prominent in the small intestine, but there is no evidence of active glucose or amino acid absorption in the colon except during the early neonatal period. Sodium transport also differs in the colon. Glucose-and amino-acid-stimulated sodium transport is a well-established property of the small intestine, so much so that oral glucoseelectrolyte solutions have been used to reduce the morbidity of cholera and other infectious diarrheal diseases of the small intestine. In contrast, glucose-coupled sodium transport does not take place in the colon and glucose-electrolyte solutions are of no benefit in diarrheal diseases of the large intestine. Sodium transport in the colon instead relies upon electrogenic transport. 20, 21 The large intestine also differs in its response to mineralocorticoids. Aldosterone markedly increases sodium transport in the colon, but it has only a modest effect in the small intestine. Net sodium absorption ceases in the colon only when the luminal sodium concentration is canine colon, accounting for up to 90% of the colonic microflora.

Most are facultative or aerotolerant anaerobes, not true obligate anaerobes. 41 Enterobacteria and streptococci are the predominant aerobic bacteria found in the canine colon. In the cat, approximately equal numbers of anaerobic and aerobic bacteria are found in the colonic lumen. 42 The colonic flora changes significantly with developmental stages. The aging canine colon becomes more readily populated by Clostridium perfringens and other obligate anaerobes, and less populated by aerobes and aerotolerant anaerobes. 41, 43 This change takes place in the ascending and descending colon, but is most significant in the descending colon where anaerobic conditions tend to predominate. Senescent changes in bacterial populations of the colon conform to the principles of successional ecology. 44 Over time, changes in pH, redox (oxidation-reduction) potential, bacterial competition, and nutrient availability facilitate the proliferation of anaerobic bacteria permitting them to eventually displace the aerotolerant forms.

The colonic flora may also be influenced by an animal's breeding and genetic background. For example, far fewer Bifidobacterium spp. are recovered from the feces of Beagle dogs than are recovered from other dog breeds. 43, 45 This represents a problem for studies of colonic bacteriology because many of the reference studies have been generated from Beagle dogs.

Diet has a major impact on numbers and types of bacteria recovered from the colon. Bacteroides spp. appear to be particularly susceptible to changes in the diet. [45] [46] [47] The protein, carbohydrate, and fiber content of the diet all appear to influence the ability of bacteria to grow within the colon. Thus, dietary history should always be considered when interpreting results of fecal or colonic bacterial cultures.

Geographic locale and environmental conditions can also influence colonic bacteriology in the dog. Bifidobacterium spp. are readily isolated from dogs from Japan but they are inconsistently found in American dogs. 41, 45 Housing conditions appear to be another confounding factor. Open housing environments 41 appear to facilitate colonization of a greater proportion of facultative anaerobic bacteria compared to closed facility conditions. 48 Motility patterns of the colon influence the bacterial ecology of the colon. The antiperistaltic activity of the ascending and transverse colon particularly facilitates the mixing of fecal material with endogenous bacteria. Abnormalities in the motility patterns of this part of the colon lead to changes and proliferation of obligate anaerobes similar to that which is found in the descending colon. 29 Disease and medical therapies, particularly antibiotics, alter the microbial characteristics of the colon. These changes are poorly understood in dogs and cats but they very likely contribute to clinical symptomatology (see Chapter 2).

History Inflammation is the most important pathophysiologic condition of the colon. Colitis is responsible for the major clinical signs of

The colon has evolved to serve two important functions: extraction of water and electrolytes from the luminal contents in the ascending and transverse colon, and control of defecation in the descending colon. This specialization of function is attributed to regional differences in colonic motility patterns. [29] [30] [31] [32] [33] Electrical slow-wave frequency and rhythmic phasic contractions are slower in the proximal portion of the colon, thus facilitating extraction of water from the fecal mass by diffusion and active transport. Retrograde giant contractions (RGCs) and antiperistalsis further facilitate the mixing of contents in the proximal colon. In contrast to that of the proximal colon, motility of the distal colon is characterized primarily by migrating spike bursts and powerful giant migrating contractions (GMCs) that propagate the fecal mass toward the rectum. 4, 33 Colonic smooth muscle generates at least four different types of contractions to perform the complex motility functions of mixing and propulsion: (a) tone, (b) rhythmic phasic contractions (RPCs), (c) RGCs, and (d) GMCs. The time course, frequency, and force generated by each of these contractions are significantly different from each other. [30] [31] [32] [33] The precise role of tone in circular muscle cells is not known, but the resulting decrease in the diameter of the colon may enhance the efficiency of the phasic contractions in mixing and propulsion. Tone is normally of small to moderate force and can last for prolonged periods of time (several minutes to hours). RPCs produce mixing and net slow distal propulsion of luminal contents in the postprandial and fasting state. Phasic contractions occur rhythmically at a few cycles per minute, last for approximately 3 to 5 seconds, and generate a moderate force (75 to 100 g). RGCs occur infrequently, last for approximately 20 seconds, generate a very strong force (>150 g), and are propagated from their point of origin into the ascending colon. RGCs facilitate mixing in the ascending colon. The GMCs are of a similar magnitude and frequency to the RGCs, but they generate mass movements from their point of origin to the anorectal junction. It has been suggested that different signal transduction pathways are used by smooth muscle cells to trigger different contractions. 34, 35 It is remarkable that the same smooth muscle cells can generate so many different types of contractions using a limited number of second messengers.

The colon contains the largest concentration of bacteria in the gastrointestinal tract, up to 10 11 organisms per gram of feces. The colonic microflora play an important role in the nutrition of the animal primarily via the production of short-chain fatty acids (SCFAs). 36 Major fiber fermentation substrates include cellulose, hemicellulose, and pectin, substrates that typically are not digested by pancreatic or intestinal amylases. Acetate, propionate, and butyrate account for more than 85% of formed SCFAs, and they accumulate in concentrations up to 150 mmol/L in the colon of dogs. 37 SCFAs are rapidly absorbed by the colonic mucosa, are readily metabolized by colonic epithelial cells, and have various physiologic effects. Among their physiologic effects, SCFAs promote differentiation and proliferation of colonocytes, 38 stimulate absorption of water and electrolytes, 39 provide 7% to 10% of an animal's overall energy requirements, 37 and influence or modify motility of the gastrointestinal tract. 40 The colonic flora is influenced by many factors, including host species, breed, developmental stage, dietary history, environmental conditions, geographic locale, colonic motility patterns, disease, and medication history.

In general, anaerobic bacteria (Bacteroides spp., Bifidobacterium spp., Clostridium spp., and Lactobacillus spp.) predominate in the hematochezia, mucus in the feces, dyschezia, abdominal discomfort, tenesmus, urgency, and increased frequency of defecation. The colon is an important target organ for inflammatory bowel disease (IBD) in the dog, whereas the upper gastrointestinal tract (stomach and small intestine) is more frequently involved in feline IBD. Clinical signs are useful in localizing the anatomic site of the diarrhea to the small or large bowel (Table 58 -2), although some animals will have diffuse involvement of the small and large intestines.

The history should include specific questions about diet, parasite control, environment, travel history, concurrent medical disease, and drug history. Dietary sensitivity reactions 1 and parasitism are major causes of colitis in many pet populations. Dietary history should include information regarding type of diet, incidence of dietary indiscretion, supplements, snacks, and treats. Information concerning previous fecal examinations and anthelmintic usage may provide useful clues to the cause of the diarrhea. Environmental history should identify other pets in the household and the composition of their diets, and any behavioral interactions or hierarchies that might influence the development of clinical signs. The travel history may yield important information about exposure to histoplasmosis, pythiosis, and heterobilharziasis, all of which have regional distributions. Concurrent medical disease (e.g., Addison disease, IBD, pancreatitis) also helps to place the current episode of colitis in context. The drug history should include information about the use of alternative and complementary medicines that could contribute to clinical symptomatology.

The physical examination may be normal in many cases of colitis. The most consistent physical examination findings are pain and irregularities of the colonic mucosa on digital rectal examination. The perineum should be examined carefully to exclude perineal diseases such as perineal hernia and perianal fistula. Physical examination may reveal other important findings, including fever (IBD, cecal or colonic perforation, fungal infection), abdominal pain (IBD, colonic neoplasia, cecal or colonic perforation), abdominal mass (colonic neoplasia, granulomatous colitis, intussusception), small intestinal thickening (concurrent small intestine IBD, small intestine lymphoma), mesenteric lymphadenopathy (small intestine IBD, small intestine lymphoma), hepatosplenomegaly (lymphoma, disseminated fungal infection), and uveitis (protothecosis, lymphoma). A scoring 

Constipation is the second most important pathophysiologic condition of the colon. Clinical signs include reduced, absent, or painful defecation for a period of time ranging from days to weeks or months.

Physical examination findings will depend on the severity and pathogenesis of constipation. Dehydration, weight loss, abdominal pain, and mild to moderate mesenteric lymphadenopathy are common findings in cats with idiopathic constipation.

Physical examination might also reveal abdominal mass (cecal or colonic neoplasia, granulomatous colitis), abdominal pain (foreign bodies, colonic perforation), autonomic neuropathy (dysautonomia), hind limb paresis (lumbar spinal cord pathology), pelvic fracture (pelvic outflow obstruction), and perineal hernia (cause or complication of constipation). For both inflammation (colitis) and constipation, the scope of the medical investigation is shaped by prior history, suspected etiology, chronicity, and signs of systemic illness (Figures 58-4 and 58-5). 3, 4 

Complete blood count, serum chemistry, and urinalysis should be considered in animals with signs of colonic disease, particularly those with signs of systemic disease. These tests may provide evidence of anemia (chronic disease, GI blood loss), leukocytosis (IBD, neoplasia, cecal or colonic perforation), eosinophilia (parasitism, Addison disease, mast cell disease, hypereosinophilic syndrome), thrombocytopenia (concurrent immune thrombocytopenia), hypoproteinemia (protein-losing enteropathy), hyperglobulinemia (IBD, infection, neoplasia), hypercalcemia (neoplasia, fungal disease), hypoglycemia (leiomyosarcoma), and hyponatremia/hyperkalemia (Addison or pseudo-Addison disease). This minimum database is also useful to screen animals prior to anesthesia and colonoscopy. If fungal, oomycete, or algal infections are possible causes in the pet's geographic area, special serologic tests are available for the diagnosis of some of these diseases (Table 58-3) . Feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV) testing are warranted in cats with unexplained, chronic diarrhea.

Direct fecal smears and fecal flotation studies should be performed to evaluate for helminth, protozoal, and some bacterial infections (see Table 58 -3). Direct fecal smears may be useful in detecting Giardia, Tritrichomonas, and Campylobacter organisms. Zinc sulfate flotation is the most accurate and practical fecal flotation test available, and it may be more sensitive for the detection of Giardia and Tritrichomonas infections. Because some animals may have intermittent shedding of helminth ova and/or Giardia trophozoites and cysts, suspected infections should always be treated with anthelmintics or antiprotozoal agents before animals are subjected to colonoscopy.

Fecal cultures should be considered in animals with suspected bacterial infections of the intestine and colon. Risk factors for bacterial Table 58 -3). The role of enteropathogenic bacteria in the pathogenesis of colitis-type diarrhea has been reviewed recently by Marks et al. 5a Culture results should always be interpreted in light of clinical signs, other findings such as coinfections, and substantiating laboratory data such as serologies or polymerase chain reaction results. Fecal cultures should not be performed for the purpose of diagnosing small intestinal bacterial overgrowth.

A number of polymerase chain reaction (PCR) and reverse transcriptase (RT)-PCR assays have been developed for gene amplification products and messenger RNAs of infectious organisms (see Table 58 -3). Assays are now available for the molecular diagnosis of Tritrichomonas foetus, Pythium insidiosum, Campylobacter jejuni, C. perfringens, C. difficile, E. coli, Salmonella spp., and B. pilosicoli, and many more are likely forthcoming. Molecular detection is the standard for infectious disease diagnosis in many instances. 6

Exfoliative rectal or endoscopic cytology may be useful in identifying etiologic agents (e.g., fungal elements, neoplastic cells) and inflammatory cells (e.g., lymphocytes, eosinophils). Rectal smears

Colonoscopy is indicated for the diagnosis of colitis-type diarrhea unresponsive to dietary modification and medical therapy, suspected colorectal neoplasia, chronic constipation, unexplained stricture, and evaluation of prior surgical or medical treatment. 11 Colonoscopy is performed after other noninvasive diagnostic tests (e.g., fecal parasitologic examination, fecal bacteriologic examination, exfoliative cytology, abdominal ultrasonography, survey ± barium-contrast radiography) have failed to diagnose the disease.

Rigid or flexible endoscopy may be performed, but flexible endoscopy provides better visualization and examination of the entire colon. The normal colonic mucosa is pink in color, smooth in texture, and glistening in appearance (Figure 58-6 ). Unlike the esophageal, gastric, and duodenal mucosa, submucosal blood vessels are readily apparent. The mucosa should not hemorrhage when abraded by the endoscope; active hemorrhage usually implies an underlying disorder such as inflammation or infection. The colonoscopic procedure should include examination of the more proximal structures-for example, ascending colon, cecum, ileocecal sphincter, and distal ileum-whenever possible. The proximal colon is an important site of inflammation, parasitism, ileocolic intussusception, cecal inversion, and neoplasia. may be obtained with a cotton-tipped applicator or conjunctival spatula during anorectal examination, or with a cytology brush at the time of endoscopy. A good correlation (specificity, 97%; sensitivity, 93%) was shown between exfoliative cytology and subsequent endoscopic or surgical biopsy in one study. 7 Additional studies are still needed to verify the diagnostic value of this test.

Survey abdominal radiographs may occasionally document colonic foreign objects, mesenteric or sublumbar lymphadenopathy, intussusception, and extraluminal compression, but survey radiographs are generally nonspecific in the diagnosis of colonic disease. Contrast studies (e.g., barium enema) are performed infrequently because of their poor sensitivity and requirement for general anesthesia. Ultrasonographic imaging has proved more useful in documenting mass lesions, lymphadenopathy, intussusceptions, and bowel thickening. Abdominal ultrasound may also be used to facilitate percutaneous aspiration of luminal masses, mucosal thickenings, and lymph nodes. 8, 9 Computed tomography (CT) colonography, also known as virtual colonoscopy, has been successfully implemented in human medicine, and has been studied experimentally in the dog. 10 advanced through the descending colon to the splenic flexure. To facilitate passage of the endoscope through the splenic flexure, the tip of the endoscope is deflected slightly upward, and the endoscope is pushed into the transverse colon. The transverse colonic mucosa is now more visible as the endoscope enters the short, straight segment of the transverse colon. At the hepatic flexure, the tip of the endoscope is deflected caudally to enter the ascending colon. While keeping the tip of the endoscope in the center of the lumen, the endoscope is advanced the full length of the ascending colon into the cecum and ileocecal sphincter. The cecum is easily inspected, and the endoscope is then advanced through the ileocecal sphincter to evaluate the distal ileum. Endoscopic biopsies may be obtained at each sequential site or during withdrawal of the endoscope at the end of the study (see Chapter 27) . Diseased tissue, nondiseased tissue, and the transition zone between diseased and nondiseased tissue should be biopsied during colonoscopic procedures. This standard helps to verify the extent of the disease, ensures that disease in the submucosa has not been missed, and provides representative tissue samples to the pathologist to diagnose the disease. 15 In some cases of severe IBD or colonic neoplasia, advanced tissue necrosis may prevent the diagnosis of the disease process in the central part of the lesion. In the absence of gross mucosal abnormalities, three to five biopsy specimens should be obtained from each of the mid-ascending, mid-transverse, and mid-descending colonic regions (see Chapter 29) .

Inflammatory diseases of the colon are frequently encountered in dogs, but appear to be less common in cats. In many instances, acute nonspecific colitis may be self-limiting. However, chronic colitis is often associated with a long, sometimes waxing and waning clinical course and specific treatment is required to resolve clinical signs. Depending on patient signalment and history, dietary indiscretion, parasite infestation, and bacterial infection are common causes that need to be ruled out. The diseases discussed in this section are classically associated with noninfectious inflammation, although it appears that bacteria may play a role in multifactorial pathophysiology.

Acute colitis is characterized by a sudden onset of sometimes explosive watery diarrhea associated with the typical clinical signs of large bowel inflammation. Affected animals may also present with vomiting and lethargy. The disease often follows ingestion of toxins (e.g., spoiled food) as a component of "garbage can enterocolitis." However, intestinal parasites and bacterial infections must be ruled out systematically (or treated empirically) if deemed a likely cause based on signalment, history, and clinical signs. Acute nonspecific colitis is usually self-limiting and carries a good prognosis; most cases respond well to symptomatic treatment, which may include fluids, use of antimicrobials such as metronidazole, and a 24-hour fast followed by feeding an easily digestible, hypoallergenic diet over the following few days. Mild cases may be self-limiting. In the absence of exposure to toxins, hemorrhagic gastroenteritis should be considered as a possible differential diagnosis for dogs with bloody diarrhea of large bowel origin.

Fecal material must be completely evacuated before the colonic mucosa can be properly examined (Box 58-1). Incomplete bowel preparation is the major reason for an unsuccessful colonoscopic examination. Patient permitting, food should be withheld for 36 to 48 hours so that fecal material does not accumulate in the colon. The patient should also be given warm water enemas and/or gastrointestinal lavage solutions. Lavage solutions are preferable to warm water enemas, 12-14 but both may be given to facilitate successful colonoscopy. Polyethylene glycol solutions are isosmotic, are administered orally, and induce a diarrhea that rapidly removes fecal material from the bowel. Large volumes may be administered without inducing significant changes in water or electrolyte balance. 12 Electrolyte solutions should be given at a dose of 25 mL/kg at 24 and 12 hours prior to colonoscopy. Warm-water enemas should be performed gently, without irritating substances, at 24, 6, and 2 hours before colonoscopy. The combination of a 36-to 48-hour food fast, gastrointestinal lavage solution, and enemas usually results in a colon that is free of fecal fluids and solids.

Endoscopic examination of the colon has been described in detail. 11 General anesthesia is induced and the patient is placed in left lateral recumbency. The tip of the endoscope is introduced into the anorectal canal, and air is insufflated to dilate the anorectal and colonic lumen. As with upper gastrointestinal endoscopy, the tip of the endoscope should never be advanced unless the lumen is in full view. While inspecting the colonic mucosa, the endoscope is inhibition of allergic responses to food allergens and protection of mucosal barrier function. 4, 5 Polymorphisms in the genes encoding TLR1, TLR2, TLR4, and TLR6 are associated with an increased risk for development of IBD in human patients and in murine animal models. 4, 5 NOD and TLRs are also a focus of attention in canine chronic enteropathies. Cultured primary canine colonocytes can express NOD2, TLR2, and TLR4 when stimulated by their respective ligands. 6 In a study investigating TLR expression profiles in endoscopic biopsies, it was found that dogs with chronic enteropathies that needed steroid treatment to keep their symptoms controlled had increased levels of TLR2, TLR4, and TLR9 messenger RNA (mRNA) expression compared with healthy dogs. 7 However, no difference in TLR expression was detected between biopsies sampled before and after clinically successful therapy, regardless of whether dogs had been treated with diet or steroids. 7, 8 Another study identified a correlation between clinical severity of disease and expression of TLR mRNA. Duodenal mucosal mRNA expression of TLR2 was markedly increased in dogs with clinically severe IBD when compared with healthy controls, and TLR2 expression was correlated with clinical severity of diseases in a linear fashion. 8 Breed differences in TLR expression profiles have been reported in dogs with IBD. German Shepherd Dogs (GSD) with IBD have increased levels of TLR4 mRNA and decreased levels of TLR5 mRNA in the intestine compared to healthy greyhounds. 8a Differences in TLR expression mimic those reported in people with Crohn's disease and have prompted genetic investigations into polymorphisms of pattern recognition receptors in dogs with IBD. In GSDs, single-nucleotide polymorphisms (SNPs) in TLR4 and TLR5 have been associated with an increased incidence of IBD. 8b SNPs in TLR5 are associated with increased risk of development of IBD in 38 other breeds, and have been shown to be functionally hyper-responsive in GSD. This particular mutation may play a role in the pathogenesis of IBD in dogs in general. 8b Finally, although it does not appear that food antigens play a direct role in the pathogenesis of human IBD, various dietary components can exert deleterious or beneficial effects on the intestinal microflora and on the intestinal mucosa, making it plausible that dietary changes could influence the inflammatory process in the mucosa of dogs with IBD. 9 To date, the effects of dietary antigens on canine and feline IBD have not been studied in detail. However, dietary treatment is viewed by most as an integral part of the therapeutic approach to chronic inflammatory GI diseases.

A number of studies have investigated the inflammatory process associated with canine and feline colitis. Immunohistochemical studies have shown T and B lymphocytes, as well as IgG-positive plasma cells to be increased in the colonic mucosa of dogs with IBD. [9] [10] [11] Semiquantitative RT-PCR has been used to evaluate cytokine mRNA expression in colonic mucosal biopsies. Human ulcerative colitis patients typically show a Th2 dominated inflammatory response. 2 In one study the prevailing cytokine mRNA expression pattern in dogs was that of a Th1 immune response. 12 Nevertheless, the accuracy of these results has since been questioned, at least in the duodenal mucosa, where the more reliable quantitative realtime RT-PCR showed a lack of difference in cytokine mRNA expression between healthy dogs and dogs with IBD. 13 However, colonic cytokine mRNA expression has not been investigated again using the more accurate amplification techniques, and it is prudent not to overinterpret the results from the initial study. To date there are no published data about cytokine expression in feline colitis, but duodenal mucosa of cats with IBD revealed a complex pattern of cytokine mRNA expression with a possible increase in Th1 cytokine mRNA expression. 14, 15 Inflammatory Bowel Disease Definition IBD is an idiopathic inflammatory disorder affecting the gastrointestinal (GI) tract of dogs and cats. Canine and feline IBD can be defined on the basis of clinical and histopathologic criteria. Clinically, IBD is diagnosed in animals with chronic (longer than 3 weeks' duration) GI signs such as anorexia, vomiting, diarrhea (small and/or large bowel in origin), and weight loss for which no other known cause of gastroenterocolitis can be documented. Therefore, affected animals fail to respond to symptomatic treatment, including parasiticides, antibiotics, and diet. 1 In addition, histopathologic evaluation reveals inflammatory infiltration of the colonic mucosa with predominantly round cells (lymphocytic plasmacytic colitis), eosinophils (eosinophilic colitis), neutrophils (suppurative or neutrophilic colitis), macrophages (granulomatous colitis), or a combination thereof. The inflammatory process can solely involve the colon (colitis) or affect the whole GI tract (enterocolitis).

Immunologic Basis of IBD IBD is a complex disease that can affect any part of the GI tract in dogs and cats. Although the exact pathogenesis of IBD in small animals has not been elucidated, research on human and experimental IBD, as well as several studies performed recently in dogs and cats, has led to the formulation of current hypotheses.

In people, IBD encompasses two main disorders: Crohn's disease can occur anywhere in the GI tract and is characterized by a transmural inflammation, whereas ulcerative colitis is restricted to the colon and is characterized by a mucosal inflammation. IBD is clearly a multifactorial disease in which physiologic interactions of the innate and adaptive immune system with luminal microbial antigens are disrupted. 2, 3 Overall, three factors are thought to be required for the development of IBD: (a) the presence of bacteria in the intestinal lumen with potential dysbiosis in the luminal microbiome; (b) defective mucosal barrier function that allows bacterial and/or food antigens to come in contact with the innate and adaptive immune cells in the lamina propria; and (c) an aberrant innate and adaptive mucosal immune response to bacterial antigens. 2, 3 In some human IBD patients, genetic alterations affecting the expression of important molecules of the innate immunity (e.g., polymorphisms in the gene encoding the nucleotide oligomerization domain 2 [NOD2]) are responsible for the abnormal recognition and response to luminal microbiota. 2 NOD2 is an intracellular pattern recognition receptor that binds to muramyl dipeptide derived from peptidoglycan common to both Gram-positive and Gram-negative bacteria.

Toll-like receptors (TLRs) are a family of transmembrane receptors with a ligand-binding extracellular domain that recognize microbe-associated molecular patterns. They are an important component of the innate immune system. In the GI tract, specific TLRs are found located on epithelial cells, macrophages, and dendritic cells. TLR2 recognizes bacterial lipopeptides, TLR4 is activated by lipopolysaccharides, and unmethylated cytosine-phosphate diester-guanine Cpg DNA found in prokaryotic genomes and DNA viruses act as ligand for the intracellular receptor, TLR9. 4, 5 Once activated, TLRs elicit an intracellular signaling cascade leading to the production of proinflammatory cytokines. However, the physiologic function of TLRs in the GI tract includes maintaining hyporesponsiveness to innocuous luminal commensals, Colonic inflammation disrupts these normal events. It may decrease the total absorptive capacity of the mucosa through loss of functional colonocytes, increased epithelial permeability and disturbance of sodium and chloride transport. 19 Additionally, colitis has direct effects on colonic motility. The colon exhibits three types of contractions: While the individual phasic contractions and the migrating and nonmigrating motor complexes produce extensive mixing and kneading of fecal material and slow net distal propulsion, the giant motor complexes (GMCs) produce mass movements and expel feces during defecation. 20 In an experimental model, dogs with acute colitis had a decrease in nonpropulsive motility and an increase in GMCs, resulting in frequent defecation and tenesmus. 21 Decreased nonpropulsive motility may be explained by disturbances of the circular colonic smooth muscle cells associated with inflammation. These include impairment of calcium mobilization, [22] [23] [24] changes in expression of key signaling molecules for excitationcontraction coupling, 25 inhibition of muscarinic signaling, 26 and increased transcription of nuclear factor kappa B (NF-κB). 27 Finally, absorptive and motility disorders may change the composition of the luminal commensal flora, which plays an important role in the maintenance of colonic function, and therefore contribute to further deterioration.

Other colonic diseases that may lead to similar clinical signs include infectious diseases (e.g., parasite infestation with nematodes or

A high proportion of dogs and cats with colitis respond to dietary therapy alone (Table 58-4) ; however, it is important to distinguish the various reasons for diet-responsive colitis. In humans, as well as in dogs and cats, adverse reactions to food can result from immunologic (food allergy) and nonimmunologic (food intolerance) mechanisms. 16 So far, in small animals, the clinical differentiation between food allergy and food intolerance relies heavily on restricted antigen dietary trials. 17, 18 All dogs and cats with GI manifestations of adverse reaction to food get better when fed a novel diet, especially if it is designed to avoid antigens from their original diet. When challenged with their original food, they all show a relapse of GI signs. However, only food-allergic dogs and cats also relapse when their low-allergen diet is supplemented with proteins from a single source such as beef, chicken, milk, or any protein that was part of their original offending food. 17 Finally, a number of animals with colitis may simply benefit from being fed a highly digestible diet. These dogs and cats may have mild IBD that responds to the novel diet, which usually also offers additional benefits, such as an improved ratio of n6-to-n3 fatty acids or the presence of prebiotics. These animals usually do not experience a relapse when fed their original diet.

The main functions of the colon include absorption of water and electrolytes (proximal colon) and storage of feces (distal colon). with broad-spectrum parasiticides such as fenbendazole (50 mg/kg PO daily for 3 days) will eliminate most GI nematodes and protozoa. Cytologic examination of rectal scrapings can reveal the presence of Histoplasma capsulatum, large numbers of neutrophils, a sign of inflammation, or increased numbers of Gram-positive rods (suggestive of overgrowth with C. perfringens). 34 Usually, diagnostic imaging (radiographs and ultrasonography) is not very helpful in cats and dogs with colitis. It may however yield useful information if the disease extends to the small intestine. When the diagnostic elimination process confirms the possibility of large intestinal IBD, evaluation of the disease severity is desirable and best performed by colonoscopy (preceded by gastroduodenoscopy in cases with small and large bowel involvement). Full endoscopic examination of the colon requires general anesthesia but remains a safe diagnostic procedure. 35 Flexible colonoscopy allows full visualization of the rectum and descending and ascending colon, as well as cecum and ileocolic junction. Additionally, it is often possible to pass the endoscope into the ileum. Changes noticed during colonoscopy may include an increase in friability, granularity, or hyperemia; changes in the numbers of lymphoid follicles; decreased visualization of submucosal blood vessels; localized colonic spasms; and localized erosions. 31 Significant edema and inflammatory infiltrate may give the mucosa a honeycomb appearance ( Figure 58-7) ; however, the colonic mucosa may also appear normal. 31 The endoscopic procedure also makes it possible to collect mucosal biopsies to evaluate the histopathologic appearance of the mucosa. As the colon can usually be easily distended, it is advisable to use an endoscope with a large-bore biopsy channel that makes the use of large biopsy forceps possible (≥2.8 mm diameter). Rigid proctoscopy/colonoscopy is an alternative method for procuring good size colonic mucosal samples.

Histopathology allows identification of neoplastic processes and differentiation between the various types of colonic inflammation. Recently, criteria for the scoring of colonic inflammation in dogs and cats have been proposed 36 ; however, there is currently no universally approved grading system. Consequently, various pathologists may give different interpretations when evaluating the same mucosal sample. 37 Lymphoplasmacytic colitis is the most common form of chronic colitis. It may occur in young dogs (often associated with diet-responsive disease) as well as in older dogs (often associated with IBD). Eosinophilic inflammation may occur in association with IBD, or result from parasite infestation. Pyogranulomatous colitis is uncommon and associated with proliferative masses (millimeters to centimeters in diameter) visible during colonoscopy or palpable rectally. Affected dogs show severe clinical signs. 38 Suppurative colitis has been reported as a probable variant of IBD in cats and often responds to the empirical treatment of colitis.

In many instances, treatment of colonic IBD can be initiated after known causes of large intestinal disease have been ruled out. Empirical treatment should focus on a dietary approach and the use of several drugs with limited side effects. A precise assessment of the disease with colonoscopy and histopathologic evaluation of mucosal samples is required prior to using glucocorticoids or other immunosuppressive drugs. These drugs can have multiple side effects and may also hamper the success of further diagnostic efforts.

Several clinical reports describe the dietary approach to dogs and cats with histologically documented chronic colitis and large intestinal IBD (see Table 58 -4). [28] [29] [30] [31] 39, 40 Diets recommended for patients with chronic colitis include elimination diets (based on a novel protozoa), infections with systemic fungi, oomycetes, algae, and bacteria. Histiocytic ulcerative colitis (HUC), another chronic inflammatory disease, can only be distinguished from lymphoplasmacytic IBD histologically. Moreover, lymphoma or other neoplasia can infiltrate the large intestine and cause identical clinical signs to those of inflammatory diseases. Finally, cecal intussusception, although rare, is another differential diagnosis of chronic noninfectious colitis. In cats with clinical signs of colitis, it is generally recommended to search for concomitant involvement of the small bowel as enterocolitis appears to occur more frequently than isolated colitis in that species.

History Dogs with IBD tend to be middle-aged (mean age: 6 to 6.5 years with a wide age range) 1,28 and older than those with diet-responsive enterocolitis (mean age: 3.5 years; range: 0.6 to 7.6). 28 In cats with lymphoplasmacytic colitis, the mean age of onset of clinical signs is similar (around 5.2 years; range: 0.5 to 10 years). 29, 30 A predilection for purebred cats was noticed in one study, 30 but no canine breed appeared more frequently affected. There is no sex predilection. Signs of chronic colitis are characterized by large bowel diarrhea with frequent defecation of small volumes of soft to watery stool, often mixed with mucus and/or fresh blood (hematochezia). Urgency to defecate and tenesmus are often noticed by the owners, especially in dogs. Although occasional vomiting is often reported, abdominal pain, weight loss, anorexia, and/or lethargy are infrequently part of the history. They may occur during severe episodes, in severely affected animals, or in those with concurrent involvement of stomach and/or small intestine. 31 Clinical signs are often intermittent, although they may be continuous in some animals. 31 A gradual deterioration to more severe disease may be observed over weeks to months.

Most dogs and cats with large intestinal IBD are in good general condition. Their nutritional status is unchanged by the disease. However, low body condition score and lethargy may be present in severe cases, or in animals with gastroenterocolitis. Without small intestinal involvement, abdominal palpation is often unrewarding, but may help ruling out space-occupying lesions affecting the colon (e.g., intussusception, neoplasia). Rectal palpation may be painful because of anal and rectal inflammation associated with colitis. The rectum may appear empty, or contain blood, mucus, and/or diarrheic stool. Abnormal surface of the rectal wall may be noticeable on rectal palpation.

Generally, complete blood cell count, serum biochemistry, and urinalysis do not reveal significant abnormalities in dogs and cats with large intestinal IBD. This may be different in animals with generalized GI inflammation: leukocytosis with neutrophilia and left shift, hypoproteinemia with hypoalbuminemia and hypoglobulinemia, and mildly to moderately increased liver enzymes can all be present in such patients. Evaluation of acute phase reactants such as C-reactive protein in the serum has delivered mixed results, 1,28,32 and is not specific for GI inflammation. The precise clinical relevance of serum markers of autoimmunity such as perinuclear antineutrophil cytoplasmic antibodies still remains to be determined in dogs with IBD, but they may be suggestive of diet-responsive disease. 33 A parasitologic examination of one or several fecal samples is necessary to rule out parasite infestation. Alternatively, empirical treatment the mucosal barrier, including an intact epithelial cell lining; the host immune system consisting of innate immunity and adaptive immunity; and microbes and food antigens in the intestinal lumen. The interplay of these three factors is important to maintain intestinal homeostasis. In the normal case scenario, antigen-presenting cells continuously sample antigens from the intestinal lumen through pattern recognition receptors (PRRs). Depending on the nature of these antigens, the signals elicited by the antigen-presenting cells drive the adaptive immune response in the appropriate direction to eradicate a pathogen. For example, in the case of a parasite, naive T cells are preferentially driven to differentiate into T-helper (Th) 2 cells that recruit eosinophils, basophils, and mast cells to kill the parasites. In the case of a pathogenic virus, the naive T cells preferentially differentiate into Th1 cells that produce cytokines such as interferon (IFN)-γ. These cytokines recruit macrophages that phagocytose and kill intracellular viruses. In the case of pathogenic bacteria being recognized, naive T cells preferentially differentiate into Th17 cells to produce proinflammatory cytokines such as interleukin (IL)-17 and IL-22. This recruits T cells and neutrophils to kill extracellular bacteria. In the case of commensal bacteria being recognized through PRRs, naive T cells preferentially differentiate into T-regulatory cells that counteract the effect of proinflammatory cytokines produced by Th17 cells. B, In the case of IBD, a primary defect in the recognition of commensals or certain pathogens by innate immune receptors may play a causative role. Mutations in PRRs lead to misrepresentation of commensals as pathogens, leading to the massive production of IL-23, driving naive T cells to differentiate into Th17 cells. These Th17 cells then produce large amounts of proinflammatory cytokines, such as IL-17, IL-22, and tumor necrosis factor (TNF). This leads to tissue destruction and epithelial cell injury, letting even more antigens pass through to the lamina propria. This inflammatory response cannot be counterregulated by regulatory T cells, leading to the characteristic inflammatory pattern seen in IBD. protein or on hydrolyzed peptides), 28, 40 and highly digestible, lowresidue diets. 29, 39 Most dogs and cats with colitis respond within 2 weeks to a diet change, some however may require up to 6 weeks. It is important to communicate the importance of exclusive feeding of the diet to the animal's owner, especially if an elimination diet is chosen. Recommendations regarding the required duration of dietary therapy after clinical remission diverge significantly. Although in one study most dogs relapsed after being fed their original pretreatment diet again, 39 many of the dogs could be switched again to their pretreatment diet after varying time periods in another study. 28 Consequently, it is important to discuss the risks and benefits of a reexposure to the regular diet with the patient's owners in each case to enable them to make an informed decision about their pet.

Dietary fiber consists of nondigestible complex carbohydrates. The addition of soluble fiber to the diet has provided additional benefits in clinical studies of canine and feline chronic colitis. 30, 31 Fermentable fibers are metabolized to short-chain fatty acids by the large intestinal flora and provide a useful source of energy to the colonocytes. Overall, they enhance structure and function of the intestinal epithelium. 41 Examples of fermentable fibers include beet pulp, psyllium, and fructooligosaccharides. Fructooligosaccharides are oligosaccharides that resist digestion in the small intestine and are fermented by the colonic bacterial flora. Their beneficial effects on the large intestine include proliferation of colonocytes by increasing blood flow to the colonic mucosa and promotion of epithelial cell differentiation into fully functional colonocytes. 41 Additionally, fructooligosaccharides are prebiotics and therefore are able to influence the composition of the large bowel commensal flora. In cats, they were reported to increase colonic fecal concentrations of Bacteroides and Lactobacillus spp. and decrease those of E. coli and C. perfringens. 42 Finally, dietary fibers also have beneficial effects on colonic motility. As a tradeoff, addition of fiber to the diet may have a negative impact on nutrient digestibility, depending on the specific fiber type. Some fibers may also delay gastric emptying time and slow small intestinal transit time. 41 Psyllium is a soluble fiber derived from the seed of Plantago ovata. It has great waterholding capacities and forms gels in water, two properties that can contribute to improvement of fecal consistency. Psyllium was very efficient when added to a highly digestible diet in the treatment of chronic idiopathic colitis using the following initial daily dosage: 0.5 tablespoons (T) for toy breeds, 1 T for small dogs, 2 T for medium dogs, and 3 T for large dogs. 31 The fiber supplement should be administered with each meal, and the dose adapted to effect.

Probiotics are live microorganisms that may be beneficial to the host GI tract. Canine-and feline-specific probiotic cocktails are available commercially. However, the achievable benefits of modification of the large intestinal flora by administration of probiotics are subject to controversy. To date, no clinical study has been able to document positive effects of probiotics in dogs and cats with chronic GI diseases, 43 even though in vitro experiments yielded promising results. 44 data do not support a decrease in PPAR in the colonic mucosa of dogs with colitis. 48 The main side effect of sulfasalazine is keratoconjunctivitis sicca (KCS). Although the exact mechanism of action is unknown, sulfapyridine is likely responsible for damaging lacrimal glands. 49 Early detection followed by treatment discontinuation is necessary to prevent the onset of irreversible KCS. Consequently, tear production must be measured at regular intervals in all dogs receiving sulfasalazine. Vomiting may also occur, and can be prevented if the drug is administered with food. Other drugs with the same mechanism of action are available and include olsalazine (two molecules of mesalamine linked by an azo bond) and other formulations of mesalamine coated with an acrylic resin that release the compound in the distal small bowel or colon. Although these drugs have not been extensively tested in small animals, KCS has been reported with their use in dogs.

Glucocorticoids are used as a second line of treatment in dogs with colonic IBD that are refractory to dietary modifications and treatment with metronidazole and sulfasalazine. Their antiinflammatory effects are partly a result of the lipocortin-mediated inhibition of phospholipase A that inhibits the cascade leading to formation of proinflammatory prostaglandin and leukotriene synthesis. Their therapeutic interest also relies on the multiple effects they have on both the innate and adaptive immune response. 50 However, because of their multiple side effects, immunosuppressive doses of prednisone should be reserved for dogs that have undergone colonoscopy, and for which a histologic diagnosis confirms the existence and type of the inflammatory infiltrate. Cats do not appear to develop as many side effects from glucocorticoid therapy as dogs. Additionally, cats may not tolerate TID medication with sulfasalazine, and are more susceptible to mesalamine toxicity. Moreover, many cats with colitis also have lesions in the small intestine (enterocolitis) on which sulfasalazine has no effect. This combination of facts makes glucocorticoids a treatment option that is often considered earlier in feline than in canine colitis patients.

Pharmacologic intervention (Table 58 -5) is required if dietary therapy fails to control clinical signs or may be initiated simultaneously to dietary changes in severe cases. Among antimicrobials, metronidazole is frequently used in the initial management of dogs and cats with colitis. Beside its antimicrobial effects against a variety of obligate anaerobic bacteria, metronidazole is also effective against Giardia spp. Furthermore, metronidazole has immunomodulatory effects. 45 It is used in dogs and cats with colitis to modify the intestinal flora (decrease in obligate anaerobes) and decrease inflammation. If a suspension is administered to a cat, metronidazole HCl is not a palatable formulation and may elicit ptyalism and anorexia. Metronidazole benzoate is the preferable formulation for feline patients, but it contains only 62% metronidazole and therefore requires a dose adjustment. Other side effects of metronidazole are rare, although cats may be more susceptible because of the probable increased half-life of the drug, and include vomiting and diarrhea. Hepatotoxicity and neurotoxicity have been reported at higher dosages. 45 Sulfasalazine consists of 5-aminosalicylic acid (5-ASA; also called mesalamine [United States] or mesalazine [Europe]) linked by an azo bond to sulfapyridine, a sulfonamide compound. 46 Most of the orally administered sulfasalazine reaches the distal small intestine and colon unchanged. There, the microbial flora breaks the azo bond and liberates both molecules. Sulfapyridine is essentially a carrier molecule and is not thought to unfold any therapeutic effect. It is absorbed, metabolized in the liver, and filtered through the kidneys. The antiinflammatory effects of 5-ASA on the colonic mucosa are associated with inhibition of cyclooxygenase and a decrease in prostaglandin and leukotriene synthesis. Moreover, 5-ASA is an activator of peroxisome proliferator-activating receptor (PPAR)-γ. 46 In dogs, PPAR-γ are expressed at a high level in gastric, duodenal, and colonic mucosal epithelial cells. 47 They inhibit pathways leading to increased NF-κB transcription and hence to production of inflammatory cytokines and chemokines. 46 However, recent 

Sulfasalazine 10 to 30 mg/kg PO TID for 4 to 6 weeks, max 1 g total dose (D) 5 to 12.5 mg/kg PO TID for 2 to 4 weeks (C) Administer with food; slowly decrease in 10-to 14-day steps to BID, then half the dose BID, then once daily; regularly measure tear production Colonic IBD refractory to diet and metronidazole inflammation and distortion of the intestinal lamina propria. The causative organism in Whipple disease is susceptible to a variety of antibiotics, such as penicillin, chloramphenicol, and tetracycline, but seems to be resistant to fluoroquinolones. T. whipplei has not yet been identified in dogs with HUC, but the recent treatment success with enrofloxacin seems to make this organism less likely to be causally involved.

In a recent publication investigating the possibility of an infectious cause for canine HUC, large numbers of coccobacilli were found in the colonic mucosa by fluorescence in-situ hybridization (FISH) in Boxers affected with HUC but not in histologically normal tissues or in the mucosa of dogs with other types of colitis. 65 Further studies using culture, cloning, and sequencing of the colonic flora from Boxers with HUC identified the bacteria to be E. coli. Electron microscopy of HUC lesions allowed identification and localization of the bacteria to the intracellular compartment of PAS positive macrophages. 65 Additionally, the intracellular material found in PAS-positive macrophages from dogs with HUC was positively labeled with polyclonal antibodies against E. coli. 66 Further classification of the virulence genes and biologic behavior of these bacteria in coculture with epithelial cells and macrophages revealed specific adhesive and invasive properties. 65 The E. coli strains associated with HUC have a similar phenotype with adhesive and invasive behavior resembling E. coli isolates that were recently associated with Crohn's disease in people. 65 In several studies, a particular strain of E. coli (LF82) could be detected in biopsies of 20% to 35% of ileal lesions in Crohn's disease, but only in 6% of ileal samples from healthy controls or other colonic inflammatory diseases. 67 Crohn's disease affects primarily the mucosa and submucosa of the ileum and colon. It resembles canine HUC in its histologic appearance, as granulomas are the main feature of the disease. As in canine HUC, some cases of Crohn's disease are responsive to treatment with antibiotics. The E. coli strain LF82 that has increasingly been associated with Crohn's disease is unusual because it adheres to and invades intestinal epithelial cells in culture 68 and has been shown to replicate within the phagolysosomes of macrophages in the granulomatous lesions 69 instead of being cleared by the adaptive immune system. There is evidence that the adhesive and invasive E. coli associated with HUC are taken up by endosomes and persist in the macrophages instead of being cleared. 65 These findings support the hypothesis that genetics play a major role in the pathogenesis of Crohn's disease, and has led to recent genome-wide association studies in canine HUC. Certain defects in pattern-recognition receptors (PRRs) of the innate immune system have long been known to be associated with the development of Crohn's disease. 70 These receptors are important for the interaction of the mucosal innate immune system with the microflora of the intestinal lumen. The default response of the gut-associated lymphoid tissue is to clear offending pathogens, but to tolerate commensal organisms from the intestinal lumen. 71 Recent evidence confirms that polymorphisms in certain PRRs, such as NOD2, result in a disturbed response of human monocytes to E. coli LF82, linking genetics with functional disease for the first time. 72 Preliminary results from genetic studies in Boxers with HUC and healthy controls point to a defect in a protein in neutrophils that leads to defective clearance in E. coli in macrophages.

The inflammatory response normally only occurs as a reaction toward pathogenic bacteria breaching the intestinal barrier, and resembles the lesions observed in the mucosa of people affected with Crohn's disease and dogs with HUC. It is therefore possible that similar defects in PRRs occur in people with IBD and in dogs with HUC. A genetic predisposition for HUC is suspected due to the In cases refractory to immunosuppressive doses of glucocorticoids, additional immunosuppressive drugs such as azathioprine (dogs only), chlorambucil (cats), and cyclosporine 51 may be helpful. Because of potential side effects and financial considerations, these drugs should be reserved for patients with well-documented colonic inflammatory disease that showed no response to any other treatment.

The prognosis for IBD is generally better when only the colon is affected. However, one retrospective study of dogs with IBD failed to find any association between localization of disease and outcome. 52 Nevertheless, the various clinical studies summarized in Table 58 -4 demonstrate that a majority of dogs and cats with colitis will respond completely to dietary modification and/or to sulfasalazine treatment. If sulfasalazine is used, it can often be discontinued after a few weeks. However, there is a risk of recurrence when the animals are switched back to their original diet or a commercial diet. Therefore, the owners of dogs and cats with colitis should be prepared to feed their pets a special diet in the long-term, and consider the financial implications of the prolonged treatment. In a few cases, colitis may be refractory to treatment. This is probably most common in cats showing predominantly large bowel diarrhea, while in reality they have a general involvement of their GI tract (enterocolitis). In dogs with IBD, several negative prognostic factors have been identified that all reflect severe involvement of the small intestine, including hypoalbuminemia, hypocobalaminemia, severe duodenal lesions, and a high clinical disease score. 28,52 Therefore, they do not appear to apply to colonic IBD.

Definition HUC is a form of IBD that occurs most frequently in young Boxer dogs, also known as granulomatous colitis of Boxer dogs. It was first described 30 years ago 53 and has since been reported to occur in many countries, including the United States, [54] [55] [56] Australia, 57, 58 Japan, and continental Europe and the United Kingdom. 59,60 HUC also occurs infrequently in other breeds, such as Mastiffs, Alaskan Malamutes, 61 French Bulldogs, 62 and English Bulldogs, 56 and has also been described in one cat. 63

The mechanisms involved in the pathogenesis of HUC in dogs have been debated for decades. The recent success of antibiotic treatment raises the question of an infectious origin; however, this hypothesis has been investigated previously. The role played by macrophages containing cytoplasmic material stained by periodic acid-Schiff (PAS) is intriguing, and early electron microscopic studies have demonstrated so-called residual bodies, which resemble bacteria-like organisms in granules of PAS-positive macrophages. 64 These particles contained parallel pairs of membranes and electron-dense particles ranging in size from 100 to 500 nm, and may have represented bacterial cell membranes. Therefore, specific infectious agents, such as Mycobacteria, Mycoplasma, Chlamydia, and Rickettsiales ssp. have all been proposed to play a role in the pathogenesis of the disease. 55 However, attempts to reproduce the disease by infecting dogs with Mycoplasma spp. have failed.

Some reports have compared human Whipple disease with canine HUC. Whipple disease is caused by Tropheryma whipplei and mainly affects the small intestine. There is a striking histologic resemblance between both diseases involving severe granulomatous preponderance of cases in young boxer dogs. In the first report of the disease in 1965, most of the affected dogs could be traced to a single ancestor. 53 Confirmation and identification of mutations in PRRs such as TLRs or NODs in boxers with HUC is still lacking. However, it seems likely that a defect in innate immunity renders dogs with HUC more susceptible to infections with specific bacteria, such as the adhesive and invasive E. coli strains described previously (Figure 58-8 ).

Typically, HUC is characterized by chronic large intestinal diarrhea in relatively young dogs. Differential diagnoses include parasitic diseases such as infestation with Trichuris vulpis or Giardia spp., bacterial infections with Campylobacter or Clostridia, infections with oomycetes (Pythium spp.) and fungal microorganisms (H. capsula tum), as well as diet-responsive diseases such as food intolerance or food allergy. Further differentials include IBD other than HUC, such as lymphoplasmacytic and eosinophilic colitis. Rectal and colonic polyps as well as neoplastic disorders, such as lymphoma or adenocarcinoma, are less likely to occur in younger animals.

The onset of disease occurs predominantly before 2 years of age. The clinical signs are those of severe chronic large intestinal inflammation and comprise diarrhea, hematochezia, increased frequency of defecation, tenesmus, and presence of excessive mucus in the feces.

Physical examination findings are normal in many cases of HUC. However, weight loss and inappetence can be seen in severe cases, and should prompt further more invasive investigations. Fresh blood and mucus can be seen upon rectal examination.

The diagnostic approach to cases with HUC is as described for chronic colitis. Typically, colonoscopy reveals sites of severe colonic hemorrhage and ulceration interspersed with stretches of normal appearing mucosa (Figure 58-9 ). Ten to 15 biopsies should be taken for histopathological analysis. Early lesions can consist of a mixed inflammatory infiltrate in the lamina propria, subjacent to degenerative epithelium. 53, 55, 73, 74 With more extensive lesions and chronic disease, the ulcers become more visible on histology with severe infiltration of the lamina propria and the submucosal regions with by macrophages and neutrophils at an early stage in their differentiation and is lost when macrophages migrate into tissues and mature. It is possible that in canine HUC recently emigrated blood monocytes progressively differentiate into tissue macrophages, and become eventually filled with PAS-positive material, while L1 expression is downregulated. 55 MHC class II molecules are normally present on macrophages. Therefore it is not surprising to find an increased MHC class II expression associated with PAS-positive macrophages in HUC. Increased T-cell numbers were observed in HUC and are reminiscent of increased numbers of CD3-positive cells seen in other forms of canine IBD, particularly lymphoplasmacytic IBD. 60 Confirmation of the presence of E. coli using FISH analysis on formalin-fixed biopsies is now recommended as part of the detailed diagnostic work-up for dogs with suspected HUC. 75a Up to 43% of dogs with HUC develop enrofloxacin resistance early in the disease process and may be refractory to treatment if they are treated without taking bacterial culture results into account. 75b

The prognosis for HUC was considered to be guarded to poor until recently. Management of HUC used to consist of various combinations of dietary modification (e.g., increasing fiber content and specific elimination diets), and antiinflammatory or immunosuppressive treatment with sulfasalazine, prednisone, and azathioprine, as described previously for the treatment of chronic colitis. Typically these strategies were not successful, and most cases had to be euthanized because of refractoriness to treatment. In recent years two reports have sparked hope for treatment of HUC: a total of 35 cases have been described and have shown a dramatic response to treatment with enrofloxacin (5 mg/kg PO once daily), or a combination protocol with enrofloxacin, amoxicillin (20 mg/kg PO twice daily), and metronidazole (10 to 15 mg/kg PO twice daily). 56 Reports of the disease almost 30 years ago also occasionally described a good response to treatment with antibiotics, namely chloramphenicol and tetracycline. 76 The response to treatment with enrofloxacin in the more recent reports was dramatic, with all dogs responding within 3 to 12 days of initiating therapy. It is particularly encouraging that several dogs were reportedly disease-free after the drug had been discontinued following a 4-to 6-week course of treatment. 56 This implies that HUC can be cured in some cases. Five dogs were rebiopsied when they were in clinical remission after completion of the antibiotic treatment. A dramatic improvement in the histologic lesions was evident in all cases, with disappearance of PAS-positive macrophages in three dogs and marked reduction in the number of macrophages in the other two cases. 56 However, care must be taken to treat dogs with HUC long enough to avoid relapse after discontinuation of treatment. In addition, it may be prudent to send intestinal biopsies for culture and sensitivity before starting treatment, so that the use of antibiotics can be tailored to the specific sensitivity profile of the cultured E. coli. 75a,77

Anal furunculosis (AF) is a chronic and painful disease of the anorectum in dogs that preferentially affects German Shepherd dogs and is characterized by inflammation, ulceration, and sinus tract formation. Clinical signs include a painful ulcerated perineal region that may cause tenesmus, hematochezia, and even anorexia and weight loss. Histologic evidence of colitis has been documented in several cases of AF. 78, 79 This association is interesting because neutrophils, macrophages, lymphocytes, plasma cells and mast cells. There is also usually marked loss of the epithelial surface in biopsies from lesions and loss of goblet cells in the entire colon. Accumulation of large PAS-positive macrophages is pathognomonic for HUC 54, 73, 75 and remains the best way to confirm the diagnosis (Figure 58-10) . In immunohistochemical studies HUC lesions are characterized by an increased number of L1-positive cells ( Figure  58 -11), as well as major histocompatibility complex (MHC) class II-positive cells, CD3-positive cells, and IgG-positive plasma cells. 60 L1 is a cytosolic calcium-binding protein, the function of which has not been described in detail in the dog. In humans, it is expressed 

Etiology Heterobilharzia americana, a fluke parasite, is the causative agent of canine schistosomiasis in North America. [1] [2] [3] [4] [5] Infection is enzootic in the Southeastern and Gulf Coast of the United States. Raccoons are considered the most important reservoir host of the parasite. Domestic and wild canid infections are uncommon, but clinically significant. The major intermediate hosts are the freshwater lymnaeid snails, Lymnaea cubensis and Pseudosuccinea columella.

Infection is acquired when free-swimming cercaria, released from the snail intermediate host, penetrate skin. The cercaria migrate through the lung and liver where they mature into adult flukes and then to the terminal mesenteric veins to reproduce. Ova are deposited in the terminal branches of the mesenteric veins and work their way through the intestinal mucosa to the bowel lumen by secretion of proteolytic enzymes. When ova are excreted in feces and come into contact with water, they give rise to miracidia that penetrate susceptible snails to reinitiate the cycle. The presence of ova in the submucosa of the small intestine and colon elicits an intense granulomatous tissue reaction. 2 Lesions are characterized by epithelioid macrophages, usually surrounding parasitic ova, admixed with varying amounts eosinophils, neutrophils, lymphocytes, and plasma cells. 1, 2 Ova that do not make it to the intestinal lumen may be hematogenously disseminated to distant sites, particularly via the portal vein to hepatic venules where ova-induced chronic inflammation can lead to hepatic fibrosis and organ failure. Ova and associated granulomatous inflammation may also be found in the pancreas and lungs.

Clinical signs range from profuse acute to chronic mucoid diarrhea and tenesmus. Signs of inappetence, weight loss progressing to cachexia, and bloody diarrhea of small bowel (melena) or large bowel (hematochezia) origin are common. Physical examination findings may include thickened loops of intestine, abdominal effusion, peripheral edema, and mild generalized lymphadenopathy. Dermatitis caused by cercarial penetration of the skin or coughing because of lung migration are uncommonly reported. Clinicopathologic abnormalities include anemia, hyperglobulinemia, hypoalbuminemia, eosinophilia, and proteinuria. Dogs with Heterobilharzia infection may present with clinical signs arising from moderate to severe hypercalcemia. 1, 6 In 2 dogs with Heterobilharzia infection, and lack of evidence for malignancy, hypercalcemia was attributed to elevated parathyroid hormone-related peptide concentrations. 6 chronic fistulation is frequently observed in people with Crohn disease. Moreover, PRRs are thought to play an important role in the pathogenesis of IBD in people and dogs, and have been the object of recent research in dogs with AF. One study found dysfunctional NOD2 responses in German Shepherd dogs with AF. 80 Moreover, a restricted allelic variation in TLR1, TLR5, and TLR6 was found in German Shepherd dogs. However, there were no significant associations between these PRR polymorphisms and AF. Nevertheless, these polymorphisms may influence innate immune responses in German Shepherd dogs and may be an important predisposing factor for the development of AF in that breed. 81 In other studies, increased prevalence of a specific haplotype of alleles of genes encoding class II molecules of the canine MHC was shown in German Shepherd dogs with AF, suggesting a possible defect in antigen presentation associated with the disease. 82 Finally, it is noteworthy that feeding a restricted antigen diet maintained more than 80% of dogs with AF in complete remission after en bloc surgical excision and anal sacculectomy, 83 and that both AF and IBD respond to treatment of immunosuppressive drugs such as prednisone and cyclosporine. 84 These similarities underline the possibility of a comparable pathomechanism for both diseases.

Typhlitis refers to inflammation of the cecum and is a rare condition in small animals.

There are few case reports that describe typhlitis in association with concurrent inflammation of the ileum and/or colon in dogs. The inflammation has been reported to be predominantly eosinophilic in one dog. Little is known about the pathomechanism of disease, but it is likely that the pathogenesis is similar to lymphoplasmacytic and/or eosinophilic IBD in the small and large intestine.

Typhlitis usually presents in combination with enteritis or colitis, and the clinical signs are associated with small and/or large intestinal chronic diarrhea. In addition, the anatomical location of the cecum makes it more likely that severe inflammation could result in signs of intestinal obstruction or pseudoobstruction. Consequently, differential diagnoses include infectious and inflammatory causes of enteritis and colitis such as T. vulpis, as well as causes for obstruction, such as foreign bodies, abscesses, inversion of the cecum into the colon, fecaliths, or neoplasia.

History and physical examination in patients with typhlitis resemble those for chronic small intestinal and/or large intestinal diarrhea. 85 In some cases, ileus or pseudoileus can occur as a consequence of obstruction of the cecum, which results in acute or chronic vomiting. 86, 87 Radiography may reveal signs of partial or complete ileus. Abdominal ultrasound may show thickening of the cecal mucosa or evidence of obstruction in the cecal lumen. Endoscopy is recommended in all cases of suspected nonobstructive typhlitis as it allows direct visualization of the mucosa and collection of multiple endoscopic biopsies.

If typhlitis occurs secondary to enteritis or colitis, the management consists of treatment of these diseases. If chronic typhlitis has led to Trichuris spp.

T. vulpis, the parasite responsible for whipworm infection, is likely one of the most common causes of chronic large bowel diarrhea in dogs. In cats, infections are rare and caused by Trichuris campanula and Trichuris serrata.

Worms of the genus Trichuris are parasites of large intestinal mucosa. Infection is transmitted by the fecal-oral route. Eggs are ingested and develop into larvae that hatch in the small intestine where they burrow into the epithelial crypts. Larvae subsequently migrate to the cecum and colon where they develop into adults. Adult worms tunnel their thread-like anterior body into the mucosa and use a mouth spear to puncture and shred tissue, blood vessels, and epithelial cells upon which they feed. 12, 13 Heavy infections may produce severe typhlitis and colitis. Cecal inversion is uncommonly reported. Factors contributing to pathogenicity and clinical severity include the number and location of adult worms, degree of mucosal inflammation, severity of anemia or hypoproteinemia, nutritional status of the host, and presence of other GI parasites and microorganisms. 14 

Trichuris spp. can infect dogs of all ages. Many, if not most, infections are asymptomatic. Characteristic clinical signs are those of mucoid large bowel diarrhea with tenesmus and hematochezia. Signs may be acute, chronic, or intermittent. Severe infections may be accompanied by eosinophilia, anemia, and hypoproteinemia. Rarely, infected dogs have serum electrolyte abnormalities consistent with hypoadrenocorticism (hyponatremia and hyperkalemia). When tested, these dogs are normoresponsive to adrenocorticotropic hormone stimulation. 15 

Characteristic bipolar operculated, thick-walled, unembryonated ova are identified by routine fecal flotation. Immature adults can cause severe disease and adults are sporadic egg producers. Accordingly, repeated fecal examination may be necessary to identify ova and negative fecal examinations do not rule out infection. Empirical treatment for occult Trichuris infection should always be performed before moving on to a more detailed, costly, and unnecessary medical investigation. Ova of the feline trichurids, T. campanula and T. serrata, may be easily confused with pseudoparasites, for example, ova of Trichuris or Capillaria spp. that parasitize feline prey and pass unaltered into feline feces.

Drugs effective for treatment of Trichuris spp. infections include fenbendazole and febantel. The latter drug is partially metabolized to fenbendazole and oxibendazole. Regular use of milbemycin oxime for heartworm prevention is also effective for treatment and prevention of T. vulpis infection. 16 Immature worms are less susceptible to drug treatment and it takes approximately 3 months for larval stages to mature to egg-laying adults. Therefore, treatment should be repeated in 3 weeks and again in 3 months. Whipworm ova survive for prolonged periods of time in the environment and dogs housed in areas that are difficult to decontaminate (e.g., on dirt) may need to be retreated every 2 to 3 months. When possible, feces should be collected and removed.

Excellent.

Diagnosis of H. americana is made by performing saline sedimentation of feces to observe ova containing miracidia and by the observation of motile miracidia released from ova when exposed to water. 7 In cases where infection is suspected, but ova are not observed in feces, diagnosis may be attempted by detection of circulating anodic antigen in serum by enzyme-linked immunosorbent assay (ELISA). 2

Treatment with high-dose praziquantel (25 mg/kg per os BID-TID for 2 to 3 days) 2,6 or fenbendazole (40 mg/kg per os once a day for 10 days) 8 is reportedly effective is resolving ova shedding and clinical signs.

The prognosis for acute infection is good. Chronic infections may result in liver fibrosis and organ failure.

Etiology Strongyloides tumefaciens is a feline threadworm parasite. Infections are rare and observed primarily in temperate regions of the United States Gulf Coast. Infections are more common in tropical and semitropical climates wherein favorable conditions for the freeliving stages of the lifecycle can be obtained.

Infective larvae penetrate oral-esophageal mucosa or skin and are carried in the circulation to the lungs. Larvae break into alveoli, migrate up the airways, and are subsequently swallowed. Adult parasites are comprised exclusively of parthenogenetic female worms that burrow into the submucosa of the large intestine. Worms, eggs, and larvae reside in submucosal, epithelial-lined cavities where they elicit adenomatous proliferation and infiltration of macrophages, neutrophils, lymphocytes, plasma cells, and connective tissue resulting in visible nodules on the mucosal surface of the colon.

Infection is usually asymptomatic, but in clinical cases the parasite causes intractable diarrhea, particularly in young cats and kittens. [9] [10] [11] [12] Adult parasites residing in the submucosa are associated with formation of whitish-colored, raised nodules and mucus on the mucosal surface of the colon. Each nodule has a central depression corresponding to an epithelial-lined pore through which the cavities communicate with the lumen of the colon. Coalescence of nodules may give the appearance of adenomatous tumors.

Embryonated ova are identified in fresh feces by fecal flotation. Larvae may be identified in feces by the Baermann technique and must not be confused with larvae of Aelurostrongylus abstrusus. Adult worms, eggs, and larvae may be observed in biopsy specimens of colonic mucosal nodules.

Fenbendazole 50 mg/kg once a day for 5 days.

Good.

occasional fresh blood and mucus. Diarrhea is semiformed to cow pie in consistency and malodorous. The anus may appear inflamed and painful; involuntary dribbling of feces or rectal prolapse may be present. Despite these clinical signs, most cats maintain good health, and normal appetite and body condition.

Feline T. foetus infection may be diagnosed by identifying the organism in feces by direct saline smear examination, selective protozoal culture, PCR using species-specific primers, or by observation of trichomonads in colonic mucosal biopsy specimens. The sensitivity of direct fecal smear examination for diagnosis of T. foetus is low (2% in cats with experimentally induced infection and 14% in cats with spontaneous disease). T. foetus trophozoites are often misdiagnosed as Giardia and can be difficult to distinguish from nonpathogenic trichomonads such as Penta trichomonas hominis. If repeated direct microscopic examination results are negative for T. foetus, feces may be cultured in commercially available pouches marketed for diagnosis of T. foetus infection in cattle (In Pouch TF, Biomed Diagnostics, White City, OR). Neither Giardia spp. nor P. hominis organisms survived in In Pouch TF for longer than 24 hours in one study; consequently, positive cultures are strongly suggestive of T. foetus infection. 30 A sensitive and specific single-tube nested PCR based on amplification of a conserved portion of the T. foetus ribosomal RNA (rRNA) gene unit from feline feces is commercially available (http://www.JodyGookin.com). Nested PCR assays are believed to be superior to fecal culture for diagnosis of infected cats. 31 Histopathology should not be relied upon to make a diagnosis of T. foetus infection, although a diagnosis can be attained if organisms are identified. 29 

Ronidazole has been demonstrated to be effective at killing feline isolates of T. foetus in vitro and eradicated T. foetus from experimentally infected cats (on the basis of PCR). 32 The recommended dose is 30 mg/kg q24h PO for 14 days. Ronidazole is not registered for human or veterinary use in the United States and is currently banned for use in food-producing animals because of human hazards. Neurotoxicosis may be a common and serious side effect. Therefore, treatment with ronidazole should only be considered in cases of confirmed T. foetus infection where informed consent has been obtained. Follow-up testing by PCR is recommended if diarrhea persists longer than 2 weeks post treatment. Importantly, negative results should be interpreted with caution as PCR cannot prove the absence of infection and prolonged asymptomatic carriage of the organism after antimicrobial therapy may be common.

For single-cat households where reinfection is improbable, the prognosis for eradication of T. foetus infection with ronidazole is generally good. When left untreated, 88% of cats with T. foetus infection had spontaneous resolution of diarrhea within 2 years (median: 9 months; range: 5 months to 2 years). Time to resolution of diarrhea was significantly longer for cats from multiple-cat households, and those receiving a variety of different diets and antimicrobial drugs in an attempt to treat the condition. Importantly, spontaneous resolution of diarrhea does not imply recovery from infection, as 57% of these cats remain infected with T. foetus as determined by PCR when performed 2 to 5 years after diagnosis. 33

Balantidium coli is a ciliated protozoan that primarily infects swine and nonhuman primates. 17 The infection is rare in dogs [18] [19] [20] [21] [22] and is frequently associated with exposure to swine. Trophozoites reside in the colon and result in ulcerative colitis. 19 Dogs are frequently coinfected with T. vulpis. 18, 20 Clinical signs consist of chronic hemorrhagic colitis. Diagnosis is based on demonstration of large ciliated protozoa with prominent macronuclei in fresh saline smears of diarrheic feces or cysts in feces following zinc sulfate flotation. The distinctive macronuclei of the trophozoite and cyst can only be seen after staining. Treatment for any concurrent helminth infection may alone be curative in some cases. 20 Because of their effectiveness in people, specific therapy for B. coli is likely to be attained with tetracycline or metronidazole.

Entamoeba histolytica is the causative agent of human amebic dysentery. Infection in dogs 23, 24 and cats is rare and acquired by ingestion of food or water contaminated by human or nonhuman primate feces containing infective cysts. Trophozoites dwell in the lumen of the colon and invade the submucosa by secreting lytic factors that allow them to undermine and ulcerate the mucosa. These pathogenic effects result in ulcerative to necrotic colitis and bloody, mucoid large bowel diarrhea. Rarely, trophozoites disseminate to other organs. 24 Diagnosis is made by finding ameboid trophozoites in wet-mount preparations of fresh diarrheic feces, quadrinucleated cysts in feces following zinc sulfate flotation, or trophozoites in colonic biopsy specimens. Treatment with metronidazole alleviates clinical signs of colitis, but dogs may continue to shed trophozoites. 25

Etiology T. foetus is a flagellated protozoan characterized by three anterior flagella and an undulating membrane. Trichomonads are obligate parasites of warm, moist and anaerobic sites within the gastrointestinal or genitourinary tract of their hosts. Trichomonads do not form cysts, reproduce by binary fission, and are transmitted directly from host to host in the form of trophozoites. T. foetus was first identified as a cause of chronic large bowel diarrhea in cats in 2003 and the duration of its existence in cats prior to that time is unknown. 26 The prevalence of T. foetus infection is high among densely housed cats (31% of 117 cats from 89 catteries sampled at an international cat show). 27 

In cats, T. foetus colonizes the distal ileum and colon where trophozoites can be found in close proximity to the surface of the mucosa or in the lumen of colonic crypts. 28 Less commonly, subepithelial invasion of trichomonads may also be observed. Inflammatory infiltrates consist of plasma cells, lymphocytes, and neutrophils. 29 

Cats with symptomatic T. foetus infection are generally young. Asymptomatic infection in older cats may be common. Cats originating from a cattery (e.g., purebred) or shelter appear to be at increased risk for infection because of a history of dense housing. A true breed predisposition has not been shown. 27 Clinical signs are characterized by a waxing and waning large bowel diarrhea with

Depending on severity of clinical signs and systemic involvement, prognosis can vary from guarded to good.

Etiology P. insidiosum is an aquatic oomycete.

In an aquatic environment, P. insidiosum releases motile biflagellate zoospores that cause infection by penetrating and encysting in damaged skin and gastrointestinal mucosa. Gastrointestinal pythiosis is characterized by eosinophilic and pyogranulomatous inflammation and necrosis that localizes predominantly in the submucosal and muscular layers of the intestine 40 resulting in severe, segmental thickening that most frequently involves the gastroduodenal and ileocolic sections of the GI tract. However, multisegmental lesions and diffuse involvement of the GI tract have been described. [40] [41] [42] [43] Infection may extend directly to adjacent tissues including the mesenteric lymph nodes, blood vessels, pancreas, uterus, and prostate. 40, 41, 44 Clinical Examination Pythium is identified most often in young, male, large breed dogs with recurrent exposure to warm freshwater habitats. 40, 45 Gastrointestinal or cutaneous disease may be present, but are rarely found together in the same patient. 45 Gastrointestinal pythiosis in cats appears to be rare. 45 In dogs, GI pythiosis typically results in clinical signs of weight loss, vomiting, diarrhea, and hematochezia in association with a palpable abdominal mass on physical examination. 45 Hematologic and serum biochemistry abnormalities may include anemia, eosinophilia, hyperglobulinemia, and hypoalbuminemia. Cutaneous lesions consist of nonhealing wounds and invasive masses that contain ulcerated nodules and draining tracts. 45 Diagnosis A tentative diagnosis of gastrointestinal pythiosis is made by deep wedge biopsy of affected segments of intestine wherein broad, sparsely septate, and occasionally branching hyphae are demonstrated after staining with Gomori methenamine silver or anti-P. insidiosum antibodies. 45 Definitive diagnosis of P. insidiosum can be made using a species-specific nested PCR assay applied to DNA extracted from cultured isolates, appropriately preserved tissue samples (frozen at −70°C (−94°F) and stored in 95% ethanol at room temperature), or paraffin-embedded specimens. [45] [46] [47] Alternatively, a soluble mycelial antigen-based ELISA or Western analysis may be used to detect anti-P. insidiosum antibodies in the serum. 48 

The treatment of choice for P. insidiosum infection is aggressive surgical resection. In the GI tract, 3-to 4-cm surgical margins (beyond tissue pathology) are recommended. 45 Because of frequent postoperative recurrence, postsurgical medical therapy with itraconazole (10 mg/kg PO q24h) and terbinafine (5 to 10 mg/kg PO q24h) is recommended. 45 Medication should be continued for 2 to 3 months at which time ELISA serology should be performed and compared with presurgical values. Medical therapy should be continued until serologic results (checked at 2-to 3-month intervals) are negative for P. insidiosum antibodies. 45 Medical therapy alone for treatment of pythiosis is unrewarding; this may be attributed to the

Etiology H. capsulatum is a dimorphic fungus whose free-living mycelial stage flourishes in warm, moist, and nitrogen-rich (contaminated with bird or bat excrement) soil. Although sporadic cases may occur throughout the United States, most infections are diagnosed in animals living or traveling in the Ohio, Missouri, and Mississippi River valleys.

Fungal spores (macro-and microconidia) are inhaled and develop into yeast in the lung parenchyma. The yeast are ingested by macrophages wherein they reproduce by budding and may be disseminated via the blood and lymphatics to organs rich in mononuclear phagocytes including the GI tract, lymph nodes, liver, spleen, and bone marrow. Intestinal involvement in the absence of lung disease in many cases suggests that ingestion may also be a route of infection, however experimental studies have failed to produce GI disease reliably after oral administration of H. capsulatum spores. 34 Intestinal infection results in a granulomatous inflammatory response, mucosal ulceration, and blood loss.

Dogs with intestinal histoplasmosis are typically young, large breed, and have chronic diarrhea, inappetence, weight loss, pale mucous membranes, and fever that is unresponsive to antibiotics. 35 Although signs of large bowel diarrhea (tenesmus, mucus, and fresh blood in the feces) predominate, the small bowel is invariably involved and may result in a voluminous, watery stool, melena, and accompanying protein-losing enteropathy. Clinical signs of intestinal involvement are identified less commonly in cats. 36 Other historical and physical examination findings will depend on organ and tissue involvement.

Definitive diagnosis of intestinal histoplasmosis is made by demonstrating Histoplasma organisms within mononuclear phagocytes by exfoliative cytology, intestinal biopsy, or tissue aspirates. Rectal mucosal scrapings, imprints of colonic biopsy specimens, and aspirates of liver, lung, spleen, and bone marrow are most productive in the dog. 34 For formalin-fixed, paraffin-embedded biopsy specimens, special staining (PAS, Gomori methenamine silver) is needed to demonstrate the organisms. Fungal culture is not recommended as this fosters growth of the mycelial phase, thereby increasing the risk of human inhalation of infective microconidia. Serologic and intradermal skin tests to diagnose histoplasmosis currently lack suitable sensitivity and specificity for clinical use.

Itraconazole (10 mg/kg PO q12-24h) is the drug of choice for treatment of systemic histoplasmosis. 34, 37 Amphotericin B may be combined with itraconazole in cases of severe or fulminating infection. In general, treatment is continued for 2 to 3 months beyond remission of clinical signs and for a minimum of 4 to 6 months. Symptomatic treatment may alleviate clinical signs of intestinal disease. Recommended therapies have included dietary modification (highly digestible diet for small intestinal disease, increased fiber diet for large intestinal disease), antibiotics for control of intestinal bacterial overgrowth, direct antidiarrheal drugs, and antiinflammatory drugs such as the 5-aminosalicylates. 38, 39 Problematic to diagnosis of disease causation is the high prevalence of many of these "pathogens" in healthy animals. Table 58 -6 summarizes the bacterial agents to which large intestinal disease have been attributed, their prevalence in normal dogs, clinical signs in symptomatic dogs, diagnostic approaches to their recognition, and efficacy of available tests for determining disease causation.

Anaerobiospirillum spp. are small, Gram-negative, spiral bacteria that can be isolated from the throat and feces of normal dogs and cats. In a small number of cats, infection is associated with subacute to acute ulcerative or necrotizing ileocolitis with secondary sepsis. In histologic sections of intestine, Anaerobiospirillum were observed in intestinal crypts after staining with Giemsa or Steiner stains, and identified by 16S rRNA gene PCR. 51 Treatment in cats has not been described.

Etiology Infection of the mammalian large intestine by diverse populations of spirochetes has been recognized for many decades. Their role in causation of disease is still poorly understood. In dogs, three major groups of spirochetes have been identified in feces on the basis of selective culture, multilocus enzyme electrophoresis, and 16S rRNA gene sequence data: B. pilosicoli, Brachyspira canis, and Brachyspira alvinipulli. 52, 53 Pathophysiology Pathogenic spirochetes intimately attach to the apical membrane of cecal and colonic epithelial cells. The mechanism(s) by which their cellular interaction results in diarrhea remains unclear. Spirochetes can be found in large numbers in the colonic crypts of normal dogs. In dogs with diarrhea, spirochetes can appear in the feces in large numbers. Whether the spirochetes are causal to the diarrhea or alternatively, mechanically dislodged from the crypts by diarrhea induced by other etiologic factors, remains an area of active debate. In a small number of cases, it has been observed that B. pilosicoli can be isolated from dogs with diarrhea and intestinal spirochetosis, whereas B. canis were commonly isolated from healthy dogs. 53, 54 Furthermore, B. pilosicoli will attach to cecal epithelial cells from chicks, whereas B. canis will not. 55 Accordingly, the current presumption is that B. pilosicoli may be pathogenic and B. canis commensal. A characteristic, but not invariable feature of B. pilosicoli infection is the attachment of one pole of the spirochete to the intestinal epithelium, resulting in a dense "false brush-border." 53, 56 Other pathologic changes include colonic inflammation, thickening of the colonic mucosa, and enlarged Peyer patches and lymphoid follicles.

Limited descriptions of diarrhea attributed to B. pilosicoli have been reported in dogs housed in pet shops and research colonies. 54, 57 Diarrhea has been variably characterized as mucohemorrhagic, watery, or mucoid. 58 Diarrhea appears to be more common in puppies or when intestinal function is compromised by concurrent disease.

A diagnosis of B. pilosicoli infection can be based on anaerobic culture of feces in selective media for isolation of spirochetes and multilocus enzyme electrophoresis, or demonstration of B. pilosicoli 16S rRNA genes in fecal samples or cultures by means of PCR.

absence of cell membrane ergosterol (the target of most available antifungal drugs) in oomycetes.

Most dogs with GI pythiosis are presented late in the course of infection when complete excision is not possible. The anatomic site of the lesion may also preclude complete resection. Accordingly, the prognosis in most patients is guarded to grave.

Etiology P. zopfii and P. wickerhamii are achlorophyllous algae that are ubiquitous to raw and treated sewage, slime flux of trees, and animal wastes with secondary contamination of the environment. P. zopfii is responsible for disseminated infections in dogs, whereas P. wickerhamii is responsible for cutaneous infections. Only the cutaneous form of infection has been described in cats.

It is presumed that P. zopfii is ingested by susceptible hosts, passes through the GI tract, replicates by endosporulation in the colon, and is subsequently disseminated to other organ systems via the blood and lymph. The kidney, liver, heart, brain, and eye are the most common sites of systemic dissemination. Inflammatory infiltrates are minimal in active lesions. Less commonly, however, pronounced granulomatous or pyogranulomatous inflammation may be observed.

Prototheca infection is predominantly identified in immunocompromised hosts. The most frequently reported clinical sign is intermittent and protracted bloody large bowel diarrhea. Other clinical signs depend on the organ systems involved and include acute renal failure, central vestibular disease, and posterior granulomatous uveitis.

Diagnosis of protothecosis requires identification of the organisms by cytology, histopathology, or culture for Prototheca spp. High-yield, minimally invasive samples for diagnosis of disseminated disease include rectal scrapings, and urine for sediment examination and standard aerobic culture. 49 More invasive samples obtained by vitreocentesis, cerebrospinal fluid tap, or biopsy may be required as indicated by the existence of disseminated disease.

Based on previous reports, and in the absence of susceptibility data, P. zopfii infection in dogs should be treated with amphotericin B alone or in combination with itraconazole. Aminoglycosides or tetracyclines should also be considered. 50 

The prognosis for disseminated P. zopfii infection is guarded to grave. Treatment may prolong the course of infection, but the outcome is uniformly fatal.

Bacterial causes of large intestinal disease in dogs are numerous and increasingly recognized with the advent of molecular diagnostics. 

Generally good.

Etiology Clostridium difficile is a Gram-positive, anaerobic, spore-forming bacillus. These bacteria are the most common cause of nosocomial and antibiotic-associated diarrhea in people. C. difficile can be cultured from the feces of up to 40% of normal dogs and cats, with most of these isolates being toxigenic (containing toxin genes). [60] [61] [62] [63] [64] Pathophysiology Diarrhea is mediated by toxigenic strains of C. difficile; that is, those that produce cytotoxic proteins of which toxin A (an enterotoxin) and toxin B (a cytotoxin) are best characterized. Both toxins mediate glycosylation and inactivation of Rho-GTPases (guanosine triphosphatases), resulting in depolymerization of F-actin, loss of epithelial integrity, and cell death. In the lamina propria, toxin A stimulates the synthesis of prostaglandins by macrophages, release of substance P, and degranulation of mast cells. Collectively these effects promote intestinal fluid loss and inflammation. There have been no studies to date evaluating the sensitivity of canine intestinal epithelia to either toxin A or B.

Reports clearly attributing diarrhea to C. difficile infection are uncommon and experimental infections have not produced diarrhea to date. Although antibiotic administration is a predisposing factor for C. difficile-associated disease in humans and horses, this does not appear to be a predisposing factor for dogs, although carriage of C. difficile may be more common in a hospital setting. 62, 65, 66 Dogs with suspected C. difficile-associated diarrhea commonly have signs consistent with concurrent involvement of the small and large intestine and occasionally, hemorrhagic gastroenteritis. 65 

In dogs, there has been no significant association between isolation of C. difficile (toxigenic or nontoxigenic) and the presence of diarrhea. 62, 64, 66, 67 Toxigenic C. difficile can be isolated from up to 94% of neonatal dogs in the absence of clinical signs of disease. 68 An association has been documented between immunodetection of toxin A in feces and clinical signs of diarrhea in the dog, 66,67 although toxin A was also detected in some dogs without diarrhea. In general, a diagnosis of C. difficile-associated diarrhea is supported by laboratory detection of toxin A or B by ELISA. Commercially available assays for detection of toxin A and B have unacceptably low sensitivity when applied to feces, but have reasonably good sensitivity and specificity when applied to culture isolates. 64 

Metronidazole is the drug of choice for treatment of dogs and cats with C. difficile-associated diarrhea. 69, 70 Metronidazole resistance among canine isolates appears to be absent or low. 71

The best treatment for Brachyspira spp. infection has not been identified.

Likely good, although specific treatment outcomes in dogs with confirmed infection have not been reported.

Campylobacter spp. (C. jejuni, Campylobacter coli, Campylobacter hel veticus, and Campylobacter upsaliensis) are Gram-negative, microaerophilic, gullwing-shaped and motile, bacterial rods. Campylobacter can be cultured from the feces of up to 90% of normal dogs and cats, especially in young animals housed in dense populations such as breeding facilities and shelters.

Campylobacter is acquired from contaminated food and water sources and transmitted in contaminated facilities by a fecal-oral route. Campylobacter replicate in the lumen of the GI tract, penetrate the mucus lining of the intestine, adhere to the intestinal epithelium, and are variably internalized into the host epithelial cells. Virulence factors are expressed by different Campylobacter isolates and include enterotoxins, cytotoxins (e.g., cytolethal distending toxin), and adherence/invasion proteins. Lesions induced by Campylobacter infection include typhlitis and colitis characterized by epithelial cell death and attenuation, loss of the microvillus brush-border, depletion of goblet cells, and infiltration of colonic crypts by neutrophils culminating in the formation of microabscesses. The factors responsible for inciting resident Campylobacter to become invasive have yet to be determined, although changes in intestinal microflora, the presence of concurrent enteric pathogens, immunoincompetence, and poor environmental hygiene likely play contributory roles.

Dogs and cats with Campylobacter-associated diarrhea are typically young puppies or kittens, stressed by hospitalization, travel, concurrent disease, or dense housing conditions. Diarrhea ranges from mild loose feces, to watery diarrhea, to bloody mucoid diarrhea. Inappetence, vomiting, fever, and leukocytosis may also be present. Concurrent infections with other enteric pathogens, such as parvovirus, Giardia, and Salmonella, may play a synergistic role and worsen clinical signs.

As a result of the high prevalence of Campylobacter in normal and diarrheic dogs and cats, demonstration of the organisms in feces is not indicative of disease causation. Methods used to demonstrate Campylobacter include (a) phase-contrast or darkfield examination of fresh wet mount preparations of feces for characteristic darting motility; (b) bacterial culture of feces in selective media; or (c) molecular identification of Campylobacter in feces on the basis of PCR and restriction fragment length polymorphism of specific genes. The morphologic appearance of Campylobacter cannot be adequately differentiated from Helicobacter spp. on the basis of Gram staining.

Erythromycin is the drug of choice for treatment of C. jejuni infections in people and has been shown to decrease fecal shedding 

Intestinal manifestations of EHEC infection range from asymptomatic disease, to watery or mucoid diarrhea with slight blood, 83 to anorexia, vomiting, and hemorrhagic diarrhea. [84] [85] [86] Extraintestinal sequelae of EHEC infection in dogs are reported rarely [84] [85] [86] and have not been reported in the cat. In these cases, hemorrhagic diarrhea is followed by a hemolytic uremic syndrome characterized by a triad of acute renal failure, microangiopathic hemolytic anemia, and thrombocytopenia.

A diagnosis of EHEC infection is based on demonstration of Stx (ELISA) and/or Stx genes (PCR or in-situ hybridization) in extracts of feces or in culture isolates of E. coli obtained from the feces. Sensitivity is improved by demonstrating both the toxin and gene and by performing such assays on culture isolates, rather than feces. There is little information on potential sequence heterogeneity of Stx in the dog and cat, and accordingly, the sensitivity and specificity of commercially available tests used for demonstration of Stx genes or antigen. In Greyhound dogs, a significant association was found between the presence of diarrhea and demonstration of the stx1 gene or Shiga toxin in fecal cultures. 81 Although Shiga toxin was demonstrated in 43% of Greyhound dogs with diarrhea in the study, 25% of dogs without diarrhea also had Shiga toxin-producing E. coli present. In cats, E. coli strains isolated from feces of diarrheic animals produced verotoxin more frequently than did E. coli strains isolated from those without diarrhea. 80 Treatment Too few cases in dogs and cats have been described to make solid recommendations on the appropriateness or choice of antibiotic

Etiology C. perfringens is a Gram-positive, anaerobic, spore-forming bacillus. These bacteria also are members of the normal intestinal flora and can be cultured from 80% or greater normal and diarrheic dogs. 66, 67 Most isolates obtained from dogs are biotype A, approximately 15% of which carry the gene encoding C. perfringens enterotoxin (CPE). 72

The pathophysiology of C. perfringens infection remains poorly understood. It is speculated that in response to changes in diet, antibiotic administration, or coinfection with other intestinal pathogens, commensal enterotoxigenic strains are somehow triggered to undergo massive sporulation and synthesis of CPE. CPE binds to intestinal epithelial cells, forming pores in the plasma membrane that initiate cell death signaling pathways. Subsequent access of CPE to the basolateral epithelium induces structural damage to intercellular tight junctions resulting in increased epithelial permeability. 73 When administered orally or directly into the intestinal lumen of dogs, CPE induces fluid secretion and diarrhea. 74 CPE is one of numerous polypeptide enterotoxins that may be produced by C. perfringens. CPE-negative strains of C. perfringens may mediate diarrhea by virtue of other virulence factors (e.g., β 2 toxin).

The clinical spectrum of GI disease attributed to C. perfringens varies considerably and ranges from mild self-limiting diarrhea to fatal acute hemorrhagic gastroenteritis. C. perfringens is believed to be a major cause of acute, nosocomial large bowel diarrhea that begins with 1 to 5 days of boarding or kenneling. Clinical signs of large intestinal diarrhea including mucus, increased frequency, tenesmus and hematochezia are most often attributed to C. perfringens. However, acute and chronic diarrhea of both large and small bowel origin have been described.

Diagnosis of C. perfringens as a causative agent of diarrhea remains highly problematic. At present, the optimum diagnostic approach is demonstration of CPE (protein) in feces by ELISA (C. perfringens Enterotoxin Test, TECHLAB, Blacksburg, VA) in conjunction with PCR, performed on culture isolates, for the presence of the cpe gene. Although immunodetection of CPE has been significantly associated with diarrhea in dogs, CPE is also detected in dogs without diarrhea, 66, 67 and available methods for immunodetection of CPE have poor sensitivity and specificity. Fecal culture or endospore enumeration are unreliable tests for establishing C. perfringens infection in the dog because the bacteria are commensal and there appears to be no association between fecal endospore numbers and presence of diarrhea or between spore counts and detection of CPE. 66, 67, 75 Treatment Drugs commonly used for treatment of C. perfringens diarrhea include ampicillin, erythromycin, metronidazole, and tylosin. Because of a high incidence of resistance, the use of tetracyclines is discouraged. 71

The prognosis for recovery is excellent.

Treatment consists of supportive care, parenteral fluid therapy, and administration of antimicrobial drugs with Gram-negative activity including amoxicillin-clavulanate, first-or second-generation cephalosporins, or enrofloxacin.

Prognosis depends on the cause and severity of concurrent intestinal infectious disease. Death in puppies with EPEC and concurrent enteric infection is common. Table 58 -7 discusses the section of intestine most commonly affected, type of intestinal lesion(s), invasiveness, virulence characteristics, and mechanism of diarrhea of enteric E. coli infecting dogs.

Etiology Salmonella are motile, non-spore-forming, Gram-negative bacterial rods. The species most commonly isolated from diseased animals and people is Salmonella typhimurium. S. typhimurium is ubiquitous in the environment because of direct or indirect fecal contamination of food, water, or fomites. In dogs, infection is most commonly acquired through the practice of feeding raw, 90,91 dehydrated (e.g., dog chews made from animal hide 92 ), or improperly cooked meat products. Salmonella spp. were isolated from 80% of samples taken from a bones-and-raw-food diet and from 30% of fecal samples from dogs fed the diet. 91 A conservative prevalence of Salmonella infection in clinically healthy or hospitalized dogs is 1% to 36% and from healthy cats is 1% to 18%. 93 Pathophysiology Following ingestion, Salmonella adhere via fimbriae to intestinal epithelial cells and M cells. Salmonella translocates bacterial proteins into these host cells by virtue of a type III secretion system. The translocated proteins interact with Rho-family guanosine triphosphate-binding proteins to facilitate internalization of the bacteria into host cell vesicles and stimulate host cell secretion of cytokines such as interleukin-8. A resulting influx of neutrophils transmigrate across the epithelium resulting in loss of barrier integrity. A fraction of Salmonella-containing vesicles are transported to the basolateral membrane where released Salmonella enters macrophages in which they multiply and disseminate systemically. Factors contributing to susceptibility to Salmonella infection include young age, nutritional deficiency, impaired immune defense, concurrent GI infection, and disruption of the normal intestinal flora (e.g., antibiotics) leading to loss of colonization resistance. Intestinal lesions are usually confined to the distal small bowel, cecum, and colon, and consist of mucosal inflammation and epithelial sloughing.

Clinical signs of salmonellosis are most severe in puppies and kittens younger than 1 year of age and geriatric animals. Diarrhea varies from watery to mucoid, with fresh blood present in severe cases. In addition to diarrhea, other clinical signs, such as fever, anorexia, vomiting, and abdominal pain, may be present. Patients developing bacteremia or endotoxemia may be obtunded, weak, have pale mucous membranes, tachycardia, hypothermia, and vascular collapse. The clinical and pathologic features of salmonellosis may be indistinguishable from those of canine parvovirus and feline panleukopenia infection. treatment for EHEC infection. In people, treatment with antibiotics is contraindicated because of increased risk of developing hemolytic uremic syndrome as a consequence of lysis of bacteria with release of additional toxin into the lumen of the intestine. Accordingly, treatment of infection may be limited largely to supportive care.

The prognosis is likely good for hemorrhagic diarrhea alone. The prognosis is guarded for cases characterized by hemolytic uremic syndrome.

Etiology Enteropathogenic E. coli (EPEC), also termed attaching and effacing E. coli (AEEC), possess key attributes that enable them to intimately attach to intestinal epithelial cells, into which they inject bacterial proteins, and initiate intracellular signaling pathways leading to diarrhea.

Pathophysiology EPEC adhere, in part, to intestinal epithelial cells by virtue of an adherence factor plasmid that contains genes encoding bundleforming pili. The EPEC genome also contains a "pathogenicity island," called the locus of enterocyte effacement (LEE), which contains genes encoding a type III secretory system, multiple EPECsecreted proteins, a bacterial adhesin called intimin (eae), and a translocated intimin receptor called Tir. EPEC use the type III secretory system as a "molecular syringe" to inject Tir into the host cell whereupon it is translocated to the host cell membrane and serves as a receptor for the bacterial-expressed adhesin intimin. Bacterial attachment results in considerable cytoskeletal reorganization leading to the effacement of microvilli, the formation of pedestals beneath the attached bacteria and disruption of epithelial barrier function. Diarrhea is attributed to a combination of malabsorption, water and electrolyte secretion, increased permeability of tight junctions, and epithelial synthesis of cytokines and chemokines that promote mucosal inflammation.

Dogs in which EPEC infection has been described are typically younger than 1 year of age, have acute to chronic, sometimes hemorrhagic, diarrhea, and are often concurrently infected with other diarrheal agents such as distemper virus, parvovirus, coccidia, Giardia, or Cryptosporidium. 78, 87 Fatal EPEC infection has been documented in a 2-month-old kitten and an adult cat in which attaching and effacing lesions and acute mucosal inflammation were present in the ileum and colon. 88 

Diagnosis of EPEC infection is based on documentation of attaching and effacing histologic lesions, and absence of Stx. The latter is important as some strains of enterohemorrhagic E. coli can also cause attaching and effacing lesions. Attaching and effacing lesions are characterized by accumulation of F-actin beneath the adherent bacteria and can be demonstrated by transmission electron microscopy or by staining of F-actin with fluorescent-labeled phalloidin. In dogs, attaching and effacing lesions have been reported in both the small and large intestine. Studies seeking to diagnose EPEC by demonstration of LEE-associated genes in feces have found such genes to be commonly present in the flora of both healthy and diseased individuals. 89 

The prognosis for enteritis alone is generally good. The prognosis for patients with disseminated disease, endotoxemia, or sepsis is more guarded. Some patients may remain chronic carriers with recrudescence during periods of stress or unrelated disease.

Y. enterocolitica and Yersinia pseudotuberculosis are motile, Gramnegative, coccobacilli that can be isolated from the feces of clinically normal dogs and cats. Yersinia has been cultured on rare occasions from the feces of dogs and cats with abdominal discomfort or bloody diarrhea. [95] [96] [97] Viruses

Although uncommon, colonic disease may be a primary manifestation of feline infectious peritonitis (FIP) infection in the cat. 98, 99 Clinical signs of diarrhea or constipation may be present. Physical examination reveals a palpable abdominal mass of the colon or ileocecocolic junction. Histopathology is consistent with pyogranulomatous inflammation with intralesional feline coronavirus demonstrable by immunohistochemistry. In the majority of cases reported,

Isolation of Salmonella organisms is the most definitive means of confirming infection. Because of the high prevalence of asymptomatic carriage of Salmonella, isolation from normally sterile samples (e.g., urine, blood) may allow a definitive diagnosis and indicate disseminated disease. In addition, failure to isolate Salmonella does not rule out infection because of the fastidious nature of Salmonella in culture. Use of PCR for identification of Salmonella in dogs has been described 94 but is not yet widely applied.

Treatment varies according to the severity of the clinical signs. Acute gastroenteritis, without clinical signs of systemic disease may be treated with fluid therapy and supportive care. Antibiotic therapy may prolong fecal shedding and induce drug resistance and is therefore reserved for patients with severe hemorrhagic diarrhea, history of immunosuppression, suspected or documented septicemia, evidence of systemic inflammatory response syndrome, or a combination of these symptoms.

Antibiotics reported to be effective for treatment of Salmonella include chloramphenicol, amoxicillin, trimethoprim-sulfa, and enrofloxacin. Posttreatment cultures should be performed to confirm eradication, and pet owners should be advised of the public health importance of the disease. 

With some ileocolic intussusceptions, the intussuscepted bowel may protrude through the anus and must be differentiated from a rectal prolapse. This is accomplished by passing a blunt probe between the protruding segment and the anal sphincter. If the probe can be passed cranial to the pubis without reaching a fornix, then the protruding bowel is the apex of an intussusception rather than rectal prolapse. Survey abdominal radiographs are often nondiagnostic, but may reveal distention and obstruction proximal to the intussusception (Figure 58-12) . Barium-contrast studies (barium enema or upper GI series) are often diagnostic, but abdominal ultrasonography is the preferred method of diagnosis. The appearance of a target-like mass consisting of two or more hyperechoic and hypoechoic concentric rings in transverse section or the appearance of multiple hyperechoic and hypoechoic parallel lines in longitudinal section is virtually diagnostic of an intussusception (Figure 58-13 ). 6 The ultrasound scan might also identify a mass associated with the intussusception. Endoscopy may be performed in suspected cases of suspected neoplasia, otherwise endoscopy does not confer any additional benefits over abdominal ultrasound or CT scanning.

The surgical management of ileocolic intussusception involves either reduction or resection, and anastomosis, or both. 7, 8 Secretory diarrhea may persist following relief of the obstruction and affected animals may need continuous crystalloid and colloidal therapy. If possible, the ileocecal sphincter should be preserved to reduce reflux and contamination of the distal small bowel. Cecocolic intussusceptions or inversions should also be treated with surgical resection. Surgical resection of the cecocolic intussusceptions is generally curative. Enteroplication procedures have been recommended, 9 but they do not appear to reduce recurrence rates. 7, 8 

The most common complications following treatment of intussusception are recurrence, dehiscence of the anastomosis, ileus, intestinal obstruction, peritonitis, and short bowel syndrome. The cats were euthanized or died from the effects of multisystemic FIP infection.

Intussusception is an invagination of one segment of the gastrointestinal tract into the lumen of an adjoining segment. The intussusceptum is the invaginated segment of the alimentary tract, whereas the intussuscipiens is the enveloping segment. Invagination may occur in an antegrade (aborad) or retrograde (orad) direction, but is most commonly in the antegrade direction. Any portion of the alimentary tract may be involved, but enterocolic intussusceptions account for almost two-thirds of the published cases in dogs and cats. Enterocolic intussusceptions can be further divided into three types: cecocolic (or cecal inversion), with the inverted cecum forming the apex 1 ; ileocolic, with the ileum forming the apex; and ileocecal, with the ileocecal junction forming the apex. 2 Of these three forms of enterocolic intussusception, the ileocolic intussusception is the one most frequently encountered in clinical practice. A number of conditions are reported to predispose to intussusception, including intestinal parasitism, viral enteritis, foreign bodies, and masses, but in dogs and cats most intussusceptions are idiopathic. [3] [4] [5] 

The initiating events in an intussusception are often difficult to identify retrospectively, but all intussusceptions appear to share three important features: (a) inhomogeneity in a bowel segment, a region in which the gastrointestinal tract undergoes a sudden anatomic change in diameter (e.g., ileocolic junction) or a bowel segment that is either flaccid or indurated; (b) mechanical linkage of nonadjacent segments, which can be intraluminal (e.g., linear foreign bodies or parasites) or extramural (e.g., fibrous adhesions or bands); and (c) peristaltic activity of the gut. 2 Invagination begins as a result of peristaltic contraction. Once the invagination has begun, its progress may be rapid, involving as much as several centimeters of intestinal tract within just a few hours. Invagination and intussusception result in luminal obstruction, which may be partial or complete. Obstruction usually results in distention of the bowel segment proximal to the intussusception. The degree of distention is dependent upon the completeness and duration of the obstruction, volume of fluid secretion, degree of vascular compromise, and volume of gas production from bacterial fermentation. Because the mesentery and blood supply are included in the invaginating segment, vascular compromise can occur, which initially leads to intramural hemorrhage and edema and eventually to ischemia and necrosis of the bowel. Full-thickness necrosis may ensue but perforations are rare.

The most important clinical signs with ileocolic intussusceptions are intermittent vomiting, progressive loss of appetite, mucoid bloody diarrhea, and a palpable cylinder-shaped mass in the cranial abdomen. Abdominal pain is not a consistent finding in affected animals. Clinical signs may persist for several weeks and hematochezia, and tenesmus. Cachexia is a common physical examination finding. Other historical and physical examination findings (dyspnea, cough, ascites, lameness, oropharyngeal ulcerations, chorioretinitis, neuropathy) will depend upon organ and tissue involvement. The small intestinal form of histoplasmosis is described in more detail in Chapter 57.

Organism identification is required for definitive diagnosis. The most common means of organism identification is cytology. Cytology from affected tissue reveals pyogranulomatous inflammation, often with numerous small, round to oval intracellular yeast cells (2 to 4 µm in diameter) characterized by a basophilic center and a light halo. Exfoliative cytology during colonoscopy is particularly useful in diagnosing the disease. Histopathology is helpful if cytology is nondiagnostic or inconclusive. Multiple endoscopic colonic biopsies are usually sufficient to diagnose the disease. The yeast form does not stain well with routine hematoxylin and eosin stains, so special stains such as PAS and Gomori methenamine silver stain are often used to demonstrate organisms. Fungal culture from affected tissue can be used for diagnosis but is rarely needed in clinical cases. Currently available serologies have poor specificity and sensitivity. 12 Treatment Itraconazole (5 mg/kg PO BID for 2 to 4 months) is considered the treatment of choice for feline histoplasmosis. In one study, itraconazole therapy cured histoplasmosis infections in all eight study cats. 13 Ketoconazole and amphotericin B have been described as the treatments of choice for canine histoplasmosis. With colonic involvement, additional gastrointestinal therapy may be useful in affected dogs, for example, dietary modification, treatment for small intestinal bacterial overgrowth, and direct antidiarrheal therapy. Corticosteroids may have been used successfully in the treatment of airway obstruction secondary to hilar lymphadenopathy in chronically infected dogs. 14 

There may be important species differences in prognosis although the paucity of reports, especially of prospective clinical trials, makes it difficult to generalize. It would seem that the prognosis is guarded in dogs, but fair to good in cats.

recurrence rate in dogs is reported to be between 11% and 20%. In dogs in which no surgical procedure was performed to prevent recurrence, intussusception recurred in 25% of dogs that underwent manual reduction alone and in 19% of dogs that underwent resection and anastomosis. Enteroplication does not appear to reduce recurrence rates any further. 7, 8 Indeed, 19% of dogs undergoing enteroplication in one study experienced severe complications that required a second surgery. Intestinal obstruction was a complication of the enteroplication in those patients. 8

Etiology Histoplasmosis is a systemic fungal disease of dogs and cats caused by H. capsulatum. In the environment, H. capsulatum organisms are mycelial, saprophytic soil fungi. In infected tissue or when cultured at 30°C (86°F) to 37°C (98.6°F), the organism is a yeast. The fungus is endemic throughout most of the temperate and subtropical regions of the world. Most cases of histoplasmosis in the United States occur in the central states, with the geographic distribution following the Mississippi, Ohio, and Missouri Rivers. 10, 11 Pathophysiology Infection is probably via inhalation or ingestion of infective conidia from the environment. The respiratory system is thought to be the primary route of infection in cats and dogs, although the gastrointestinal tract may also be an important route in the dog. After inhalation or ingestion, conidia transform from the mycelial phase and are phagocytized by macrophages, where they grow as facultative intracellular organisms. Hematogenous and lymphatic dissemination results in multisystemic disease. Organisms can be disseminated to any organ system, but the lungs, gastrointestinal tract, lymph nodes, liver, spleen, bone marrow, eyes, and adrenal glands are the most common organs of dissemination in the dogs; lungs, liver, lymph nodes, eyes, and bone marrow are most commonly affected in cats. Cell-mediated immunity induces a granulomatous inflammatory response in most infection. 12 Clinical Examination Dogs with gastrointestinal histoplasmosis are typically presented with mild fever, anorexia, lethargy, weight loss, vomiting, diarrhea, 

long-term cure, complete resection of infected tissue should be pursued whenever possible. Segmental lesions of the GI tract should be resected with 3-to 4-cm margins whenever possible. Medical therapy for the oomycetes has not been very promising. This may relate to the absence of ergosterol (cell membrane target of most currently available antifungal drugs) in the oomycete cell membrane. Clinical and serologic cures have been obtained in a small number of dogs following therapy with amphotericin B lipid complex (2 to 3 mg/kg QOD administered to a cumulative dose of 24 to 27 mg/kg) or itraconazole (10 mg/kg q24h for 6 to 9 months).

Unfortunately, most dogs with GI pythiosis are not presented to the veterinarian until late in the course of the disease, when complete excision is not possible. The anatomic site of the lesion (e.g., pylorus or ileocolic sphincter) may also prevent complete excision. Consequently, the prognosis is usually grave in most animals. 16

FIP is a well-known and widely distributed coronavirus-induced systemic disease in cats, characterized by fibrinous to granulomatous serositis with protein-rich effusions in body cavities and granulomatous inflammatory lesions in multiple organs. One of its morphologic hallmarks is a granulomatous to necrotizing phlebitis and periphlebitis. 22, 23 Affected cats develop signs caused by granulomatous lesions in target organs (central nervous system, eyes, and parenchymatous organs) and vasculitis leading to fluid redistribution into third spaces with fluid accumulation in body cavities. 22 In addition to the wellknown multisystemic condition, some unusual problems have been described, including focal pyogranulomas of the gastrointestinal tract. In a survey of 156 cats with disseminated FIP, 26 had solitary mural intestinal lesions. 24 Predominant clinical signs included diarrhea and vomiting for 3 months or less before intestinal biopsy. All cats had a mass, believed to be a neoplasm, in the colon or ileocecocolic junction. Affected intestine was markedly thickened, nodular, firm, and white, with multifocal pyogranulomas extending throughout the wall of the intestine, and the regional lymph nodes were uniformly involved. Most cats were euthanized or died within 9 months of histologic findings, many with signs of multisystemic FIP. 24

The etiologies for nonneoplastic colonic strictures include foreign bodies, postoperative complications, inflammatory disease (e.g., IBD, diffuse perianal fistula disease), and congenital malformation. 25 Postoperative complications are probably the most important cause of colonic strictures in dogs and cats, 25 which emphasizes the importance of good surgical principles in performing colonic surgery. 26 Nonneoplastic strictures of the colon are fairly rare. Nonneoplastic strictures of the rectum are more common (see Chapter 59).

The etiopathogenesis of idiopathic megacolon is still incompletely understood. Several reviews have emphasized the importance of

Etiology P. insidiosum is an aquatic oomycete that causes severe gastrointestinal pathology in a range of hosts in the tropical and subtropical climates. 15 Based on ribosomal RNA gene sequence data, members of the class Oomycetes are phylogenetically distinct from the kingdom Fungi, and are more closely related to algae than to fungi. 16 The oomycetes differ from fungi in two important properties: cell wall and cell membrane composition. Chitin is an essential component of the fungal cell wall, but it is generally lacking in the oomycete cell wall. Oomycetes also differ from fungi in that ergosterol is not a principal sterol in the oomycete cell membrane. This difference may explain why ergosterol-targeting drugs like itraconazole are less effective in the medical treatment of pythiosis. 16 

The infective state of P. insidiosum is thought to be the motile zoospore, which is released into stagnant water in warm environments, and likely causes infection either by encysting in the skin, or by being ingested into the gastrointestinal tract. Ingested zoospores encyst and adhere to the gastric, jejunal, and colonic epithelium with a polarity oriented toward the submucosa for rapid tissue penetration following germ tube eruption. Pythium induces a chronic pyogranulomatous response in the gastrointestinal tract and mesenteric lymph nodes. The gastric outflow tract and ileocolonic junction are the most frequently affected portions of the GI tract, and it is not uncommon to find two or more segmental lesions in the same patient. 17 Inflammation in affected regions is typically centered on the submucosa, with variable mucosal ulceration and occasional extension of disease through serosal surfaces, resulting in adhesion formation and peritonitis.

Weight loss, vomiting, diarrhea, and hematochezia are the most important clinical signs. Physical examination often reveals emaciated body condition and a palpable abdominal mass. Signs of systemic illness such as lethargy and depression are not typically present unless intestinal obstruction, infarction, or perforation occurs.

Ileocolonic wall thickening, obliteration of the normal layered appearance, and regional lymphadenopathy are common ultrasonographic features of canine intestinal pythiosis. 18 Of course, these findings cannot be readily differentiated from those associated with intestinal malignancy. Definitive diagnosis requires histologic demonstration or immunohistochemical staining of the organism and/ or positive ELISA or PCR assays. The histologic findings associated with pythiosis generally are characterized by eosinophilic granulomatous to pyogranulomatous inflammation with fibrosis. Affected tissue typically contain multiple foci of necrosis surrounded and infiltrated by neutrophils, eosinophils, and macrophages. Discrete granulomas composed of epithelioid macrophages, plasma cells, multinucleate giant cells, and neutrophils and eosinophils may also be observed. Pythium zoospores may be cultured directly from affected tissue in antibiotic-containing (e.g., streptomycin and ampicillin) media. More recently, sensitive and specific ELISA and PCR assays have been developed for the accurate diagnosis of pythiosis in dogs. [19] [20] [21] Treatment Aggressive surgical resection remains the treatment of choice for pythiosis in dogs. Because it provides the best opportunity for cats eventually require colectomy. Hypertrophic megacolon, on the other hand, develops as a consequence of obstructive lesions (e.g., malunion of pelvic fractures, tumors, foreign bodies). Hypertrophic megacolon may be reversible with early pelvic osteotomy or it may progress to irreversible dilated megacolon if appropriate therapy is not instituted. 5 Constipation and obstipation are earlier manifestations of the same problem. Constipation is defined as the infrequent difficult evacuation of feces but does not necessarily imply a permanent loss of function. Many cats suffer from one or two episodes of constipation without further progression. Intractable constipation that has become refractory to cure or control is referred to as obstipation. The term obstipation implies a permanent loss of function. A cat is assumed to be obstipated only after several consecutive treatment failures. Recurring episodes of constipation or obstipation may culminate in the syndrome of megacolon.

The pathogenesis of idiopathic dilated megacolon appears to involve functional disturbances in colonic smooth muscle. In vitro isometric stress measurements have been performed on colonic smooth muscle obtained from cats suffering from idiopathic dilated megacolon. 6, 7 Megacolonic smooth muscle develops less isometric stress in response to neurotransmitter (acetylcholine, substance P, cholecystokinin), membrane depolarization (potassium chloride), or electrical field stimulation, when compared with healthy controls. 6, 7 Differences have been observed in longitudinal and circular smooth muscle from descending and ascending colon. No significant abnormalities of smooth muscle cells or of myenteric neurons were observed on histologic evaluation. These studies initially suggested that the disorder of feline idiopathic megacolon is a generalized dysfunction of colonic smooth muscle, and that treatments aimed at stimulating colonic smooth muscle contraction might improve colonic motility. The lesion begins in the descending colon and appears to progressively involve the ascending colon over time. 8 

History Constipation, obstipation, and megacolon may be observed in cats of any age, sex, or breed, however, most cases are observed in middle aged (mean: 5.8 years), male cats (70% male, 30% female) of domestic shorthair (46%), domestic longhair (15%), or Siamese (12%) breeding. 1 Affected cats are usually presented for reduced, absent, or painful defecation for a period of time ranging from days to weeks or months. Some cats are observed making multiple, unproductive attempts to defecate in the litterbox, while other cats may sit in the litterbox for prolonged periods of time without assuming a defecation posture. Dry, hardened feces are observed inside and outside of the litterbox. Occasionally, chronically constipated cats have intermittent episodes of hematochezia or diarrhea as a result of the mucosal irritant effect of fecal concretions. This may give the pet owner the erroneous impression that diarrhea is the primary problem. Prolonged inability to defecate may result in other systemic signs, including anorexia, lethargy, weight loss, and vomiting.

Colonic impaction is a consistent physical examination finding in affected cats. Other findings depend upon the severity and pathogenesis of constipation. Dehydration, weight loss, debilitation, abdominal pain, and mild to moderate mesenteric lymphadenopathy may be observed in cats with severe idiopathic megacolon. Colonic impaction may be so severe in such cases as to render it difficult to differentiate impaction from colonic, mesenteric, or other considering an extensive list of differential diagnoses (e.g., neuromuscular, mechanical, inflammatory, metabolic/endocrine, pharmacologic, environmental, and behavioral causes) for the obstipated cat (Table 58- 8) . A review of published cases suggests that 96% of cases of obstipation are accounted for by idiopathic megacolon (62%), pelvic canal stenosis (23%), nerve injury (6%), or Manx sacral spinal cord deformity (5%). 1,2 A smaller number of cases are accounted for by complications of colopexy (1%) and colonic neoplasia (1%); colonic hypo-or aganglionosis was suspected, but not proved, in another 2% of cases. A definitive case of colonic hypoganglionosis was reported in an 11-week-old female domestic shorthaired cat. 3 Inflammatory, pharmacologic, and environmental/ behavioral causes were not cited as predisposing factors in any of the original case reports. Endocrine factors (e.g., obesity and hypothyroidism) were cited in several cases, but were not necessarily impugned as part of the pathogenesis of megacolon. It is important to consider an extensive list of differential diagnoses in an individual animal, but it should be kept in mind that most cases are idiopathic, 1,2 orthopedic, 1,2 or neurologic 4 in origin. Behavioral (e.g., stress) and/or environmental (e.g., competition for the litterbox) factors very likely play an important role in the development of this lesion, but this has been poorly studied in retrospective or prospective studies.

Megacolon develops through two pathologic mechanisms: dilation and hypertrophy. Dilated megacolon is the end stage of colonic dysfunction in idiopathic cases. Cats affected with idiopathic dilated megacolon have permanent loss of colonic structure and function. Medical therapy may be attempted in such cases, but most affected idiopathic cases. First or second episodes of constipation in some cats may be severe and generalized but may still resolve with appropriate treatment. Ancillary studies may be indicated in some cases. Extraluminal mass lesions may be further evaluated by abdominal ultrasonography and guided biopsy, whereas intraluminal mass lesions are best evaluated by endoscopy. Colonoscopy may also be used to evaluate the colon and anorectum for suspected inflammatory lesions, strictures, sacculations, and diverticula. Barium enema contrast radiography may be used if colonoscopy is not possible. Both colonoscopy and barium-contrast enema radiography require general anesthesia and evacuation of impacted feces. Cerebrospinal fluid analysis, CT or magnetic resonance imaging (MRI), and electrophysiologic studies should be considered in animals with evidence of neurologic impairment. Finally, colonic biopsy or anorectal manometry will be necessary to diagnose suspected cases of aganglionic megacolon.

The specific therapeutic plan will depend upon the severity of constipation and the underlying cause. 2 Medical therapy may not be necessary with first episodes of constipation. First episodes are often transient and resolve without therapy. Mild to moderate or recurrent episodes of constipation, on the other hand, usually require some medical intervention. These cases may be managed, often on an outpatient basis, with dietary modification, water enemas, oral or suppository laxatives, and/or colonic prokinetic agents (Table 58-9 ). Severe cases of constipation usually require brief periods of hospitalization to correct metabolic abnormalities and to evacuate impacted feces using water enemas, manual extraction of retained feces, or both. Followup therapy in such cases is directed at correcting predisposing factors and preventing recurrence. Subtotal colectomy will become necessary in cats suffering from obstipation or idiopathic dilated megacolon. These cats, by definition, are unresponsive to medical therapy. Pelvic osteotomy without colectomy may be sufficient for some cats suffering from pelvic canal stenosis and hypertrophic megacolon. 9 Figure 58 -15 provides an algorithm for the therapeutic approach to the constipated, obstipated, and megacolonic cat.

abdominal neoplasia. Cats with constipation caused by dysautonomia may have other signs of autonomic nervous system failure, such as urinary and fecal incontinence, regurgitation as a consequence of megaesophagus, mydriasis, decreased lacrimation, prolapse of the nictitating membrane, and bradycardia. Digital rectal examination should be carefully performed with sedation or anesthesia in all cats. Pelvic fracture malunion may be detected on rectal examination in cats with pelvic trauma. Rectal examination might also identify other unusual causes of constipation, such as foreign bodies, rectal diverticula, stricture, inflammation, or neoplasia. Chronic tenesmus may be associated with perineal herniation in some cases. A complete neurologic examination with special emphasis on caudal spinal cord function should be performed to identify neurologic causes of constipation, for example, spinal cord injury, pelvic nerve trauma, or Manx sacral spinal cord deformity.

Although most cases of obstipation and megacolon are unlikely to have significant changes in laboratory data (e.g., complete blood cell count, serum chemistry, urinalysis), these tests should nonetheless be performed in all cats presented for constipation. Metabolic causes of constipation, such as dehydration, hypokalemia, and hypercalcemia may be detected in some cases. Basal serum T 4 (thyroxine) concentration and other thyroid function tests should also be considered in cats with recurrent constipation and other signs consistent with hypothyroidism. Although hypothyroidism was documented in only one case of obstipation and megacolon, obstipation is a frequent clinical sign in kittens affected with congenital or juvenile-onset hypothyroidism. 1 Constipation could also theoretically develop following successful treatment of feline hyperthyroidism.

Abdominal radiography should be performed in all constipated cats to characterize the severity of colonic impaction, and to identify predisposing factors such as intraluminal radiopaque foreign material (e.g., bone chips), intraluminal or extraluminal mass lesions, pelvic fractures, and spinal cord abnormalities (Figure 58-14) . The radiographic findings of colonic impaction cannot be used to distinguish between constipation, obstipation, and megacolon in A B mineral oil (5 to 10 mL/cat), or lactulose (5 to 10 mL/cat). Enema solutions should be administered slowly with a well-lubricated 10 to 12 rubber catheter or feeding tube. Enemas containing sodium phosphate are contraindicated in cats because of their propensity for inducing severe hypernatremia, hyperphosphatemia, and hypocalcemia in this species. 10 Manual Extraction. Cases unresponsive to enemas may require manual extraction of impacted feces. Cats should be adequately rehydrated and then anesthetized with an endotracheal tube in place to prevent aspiration should colonic manipulation induce vomiting. Water or saline is infused into the colon while the fecal mass is manually reduced by abdominal palpation. Sponge forceps may also be introduced rectally (with caution) to break down the fecal mass. It may be advisable to evacuate the fecal mass over a period of several days to reduce the risks of prolonged anesthesia and perforation of a devitalized colon. If this approach fails,

Removal of impacted feces may be accomplished through the use of rectal suppositories, enemas, or manual extraction.

Rectal Suppositories. A number of pediatric rectal suppositories are available for the management of mild constipation. These include dioctyl sodium sulfosuccinate (emollient laxative), glycerin (lubricant laxative), and bisacodyl (stimulant laxative). The use of rectal suppositories requires a compliant pet and pet owner. Suppositories can be used alone or in conjunction with oral laxative therapy.

Enemas. Mild to moderate or recurrent episodes of constipation may require administration of enemas and/or manual extraction of impacted feces. Several types of enema solutions may be administered, such as warm tap water (5 to 10 mL/kg), warm isotonic saline (5 to 10 mL/kg), dioctyl sodium sulfosuccinate (5 to 10 mL/cat), constipation. The lubricating properties of these agents impede colonic water absorption, as well as permit greater ease of fecal passage. These effects are usually moderate, however, and, in general, lubricants are beneficial only in mild cases of constipation.

Hyperosmotic Laxatives. This group of laxatives consists of the poorly absorbed polysaccharides (e.g., lactose, lactulose), the magnesium salts (e.g., magnesium citrate, magnesium hydroxide, magnesium sulfate), and the polyethylene glycols. Lactose is not effective as a laxative agent in all cats. 13 Lactulose is the most effective agent in this group. The organic acids produced from lactulose fermentation stimulate colonic fluid secretion and propulsive motility. Lactulose administered at a dosage of 0.5 mL/kg of body weight every 8 to 12 hours fairly consistently produces soft feces in the cat. Magnesium salts are not currently recommended in the treatment of feline constipation and idiopathic megacolon. Anecdotal reports of therapeutic successes have been reported with the polyethylene glycols.

Stimulant Laxatives. The stimulant laxatives (bisacodyl, phenolphthalein, castor oil, cascara, senna) are a diverse group of agents that have been classified according to their ability to stimulate propulsive motility. Bisacodyl, for example, stimulates nitric oxidemediated epithelial cell secretion and myenteric neuronal depolarization. 14 Diarrhea results from the combined effect of increased mucosal secretion and colonic propulsion. Bisacodyl, at a dosage of 5 mg every 24 hours PO, is the most effective stimulant laxative in the cat. It may be given individually or in combination with fiber supplementation for long-term management of constipation. Daily administration of bisacodyl should probably be avoided, however, because of injury to myenteric neurons with chronic usage. 14 

Chloride Channel Activators. Chloride channels are voltagegated anion channels that allow the transport of chloride ions across cell membranes and play a critical role in fluid transport, maintenance of cell volume, and intracellular pH. 15, 16 Lubiprostone. Lubiprostone is a member of a group of compounds referred to as prostones. 17 Prostones are naturally occurring colotomy may be necessary to remove the fecal mass. Laxative and/ or prokinetic therapy may then be instituted once the fecal mass has been removed.

Laxatives promote evacuation of the bowel through stimulation of fluid and electrolyte transport or increases in propulsive motility. They are classified as bulk-forming, emollient, lubricant, hyperosmotic, or stimulant laxatives according to their mechanism of action. There are literally hundreds of products available for the treatment of constipation. Chapter 50 provides more detail about laxative agents.

Bulk-Forming Laxatives. Most of the available bulk-forming laxatives are dietary fiber supplements of poorly digestible polysaccharides and celluloses derived principally from cereal grains, wheat bran, and psyllium. Some constipated cats will respond to supplementation of the diet with one of these products, but many require adjunctive therapy (e.g., other types of laxatives or colonic prokinetic agents). 11 Fiber supplemented diets are available commercially, or the pet owner may wish to add psyllium (1 to 4 tsp per meal), wheat bran (1 to 2 tblsp per meal), or pumpkin (1 to 4 tblsp per meal) to canned cat food. Cats should be well hydrated before commencing fiber supplementation to maximize the therapeutic effect. Fiber supplementation is most beneficial in mildly constipated cats, prior to the development of obstipation and megacolon. In obstipated and megacolon cats, fiber may in fact be detrimental. Low-residue diets may be more beneficial in obstipated and megacolonic cats. Emollient Laxatives. Emollient laxatives are anionic detergents that increase the miscibility of water and lipid in digesta, thereby enhancing lipid absorption and impairing water absorption. Dioctyl sodium sulfosuccinate and dioctyl calcium sulfosuccinate are examples of emollient laxatives available in oral and enema form. Dioctyl sodium sulfosuccinate at a dosage of 30 mg/kg/day had no effect on fecal consistency in Beagle dogs. 12 Lubricant Laxatives. Mineral oil and white petrolatum are the two major lubricant laxatives available for the treatment of Dioctyl sodium sulfosuccinate or petrolatum and/or mosapride gastric emptying, and enhances small intestinal and colonic propulsive motility. 12, 22 Cisapride enhances colonic propulsive motility through activation of colonic neuronal or smooth muscle 5-HT receptors in a number of animal species. 23, 24 In vitro studies show that cisapride stimulates feline colonic smooth muscle contraction, 7,24 although it has not yet been conclusively shown that cisapride stimulates feline colonic propulsive motility in vivo. Anecdotal experiences suggest that cisapride is effective in stimulating colonic propulsive motility in cats affected with mild to moderate idiopathic constipation; cats with long-standing obstipation and megacolon are unlikely to show much improvement with cisapride therapy. Cisapride was widely used in the management of feline colonic motility disorders throughout most of the 1990s, 22, 25, 26 until it was withdrawn from the American, Canadian, and certain Western European markets in July 2000 following reports of untoward cardiac side effects in human patients. Cisapride causes QT interval prolongation and slowing of cardiac repolarization via blockade of the rapid component of the delayed rectifier potassium channel (I Kr ). 27 This effect may result in a fatal ventricular arrhythmia referred to as torsades de pointes. Similar effects have been characterized in canine cardiac Purkinje fibers, 28 but in vivo effects have not yet been reported in dogs or cats. The withdrawal of cisapride has created a clear need for new GI prokinetic agents although cisapride continues to be available from compounding pharmacies throughout the United States and other countries. A recent evidence-based data review of cisapride's efficacy in the treatment of human constipation and constipation-predominant irritable bowel syndrome (IBS) was carried out by the Cochrane Collaboration. 29 The authors concluded that "no clear benefit could be demonstrated with cisapride." 29 Tegaserod is a potent partial nonbenzamide agonist at 5-HT 4 receptors and a weak agonist at 5-HT 1D receptors. 30, 31 Tegaserod has definite prokinetic effects in the canine colon, but its effects in the feline colon are not known. Intravenous doses of tegaserod (0.03 to 0.3 mg/kg) accelerate colonic transit in dogs during the first hour after intravenous administration. 30 Tegaserod at doses of 3 to 6 mg/kg PO has also been shown to normalize intestinal transit in opioid-induced bowel dysfunction in dogs, 32 suggesting it could prove useful in other disorders of intestinal ileus or pseudoobstruction. Eventually, tegaserod was also shown to prolong the QT interval and delay cardiac repolarization as had been reported with cisapride. Tegaserod was marketed under the trade name of Zelnorm in the United States in September 2002 and subsequently removed from American and other markets in 2006. As with many other drugs in companion animal medicine, tegaserod was not licensed for the treatment of canine or feline gastrointestinal motility disorders.

Prucalopride is a potent 5-HT 4 receptor agonist that stimulates GMCs and defecation in the dog and cat. 33, 34 Prucalopride also appears to stimulate gastric emptying in the dog. 35 In lidamidineinduced delayed gastric emptying in dogs, prucalopride (0.01 to 0.16 mg/kg) dose-dependently accelerates gastric emptying of dextrose solutions. Prucalopride is marketed as Resolor by Movetis in Europe.

Mosapride citrate, a substituted benzamide, is a novel 5-HT 4 receptor agonist that increases gastric emptying in rats and dogs, and increases electrically evoked contractions in the isolated guinea pig ileum. 36, 37 Mosapride stimulates acetylcholine release from the myenteric plexus via activation of 5-HT 4 receptors, but has no real affinity for D 2 dopamine, 5-HT 1 , 5-HT 2 receptors, or α 1 -adrenoceptors. Mosapride restores gastric motility in dogs with vincristine-induced gastric hypomotility, 38 and therefore may be clinically useful in other bicyclic fatty acids formed by enzymatic oxidation of the 15-hydroxyl group of prostaglandins to the keto form. Lubiprostone is approved by the U.S. Food and Drug Administration for the treatment of chronic idiopathic constipation in humans. Lubiprostone activates type 2 chloride channels in the apical membrane of intestinal epithelial cells. This activity stimulates chloride secretion, followed by passive secretion of sodium and water (see Figure 1 -17 in Chapter 1). The fluid-induced bowel distention secondarily induces peristalsis, but lubiprostone has no direct stimulatory effect on gastrointestinal smooth muscle. Insufficient safety and efficacy data are currently available to recommend the routine use of lubiprostone in dogs and cats.

Guanylate Cyclase Activators. Activation of the guanylate cyclase-C receptor increases cyclic guanosine monophosphate, thereby inducing signaling pathways that stimulate chloride and bicarbonate secretion through CFTR chloride channel-dependent mechanisms and, to a lesser extent, CFTR chloride channelindependent mechanisms, and inhibit sodium absorption by a sodium-proton exchanger. 15, 16 Linaclotide is a guanylate cyclase-C receptor agonist and intestinal secretagogue that improves bowel symptoms and accelerates colonic transit in chronic constipation. 18, 19 Linaclotide has also been shown to attenuate nociceptive reflexes in response to colonic distention in three rodent models of visceral hypersensitivity. 18 Insufficient safety and efficacy data are currently available to recommend the routine use of linaclotide in dogs and cats.

µ-Opioid Antagonists. Postoperative ileus has multiple pathogenetic mechanisms. A dominant theme is the activation of enteric µ-opioid receptors resulting in inhibition of enteric nerve activity. 15, 16 Methylnaltrexone is a quaternary derivative of the µ-opioid receptor antagonist naltrexone. 20 N-terminal methylation reduces lipid solubility and prevents the drug from crossing the blood-brain barrier. Methylnaltrexone's reversal of opioid-induced inhibition of enteric nerve activity increase propulsion and secretory activity. Methylnaltrexone is clearly beneficial in the treatment of opioidinduced constipation; its efficacy in the treatment of postoperative ileus has not yet been definitively established. Insufficient safety and efficacy data are currently available to recommend the routine use of methylnaltrexone in dogs and cats.

Alvimopan has all of the same properties as methylnaltrexone; additionally, alvimopan accelerates colonic transit in healthy individuals, suggestive of a direct prokinetic effect. 20 Insufficient safety and efficacy data are currently available to recommend the routine use of alvimopan in dogs and cats.

Previous studies of feline colonic smooth muscle function have suggested that stimulation of colonic smooth muscle contraction might improve colonic motility in cats affected with idiopathic dilated megacolon. 6, 7, 21 Unfortunately, many gastrointestinal prokinetic agents have not proved useful in the therapy of feline constipation either because of significant side effects (e.g., bethanechol), effects limited to the proximal gastrointestinal tract (e.g., metoclopramide, domperidone, erythromycin), or market withdrawal because of cardiac 5-HT 4 effects. Some of the 5-HT 4 serotonergic agonists (e.g., cisapride, prucalopride, tegaserod) appear to have the advantage of stimulating motility from the gastroesophageal sphincter to the descending colon with relatively few side effects. Cisapride, for example, increases gastroesophageal sphincter pressure, promotes gastric emptying disorders. Mosapride is apparently without effect on distal gastrointestinal tract motility, and therefore may not prove useful in disorders of constipation. Mosapride is marketed as Pronamid by DS Pharma Animal Health in Japan.

Misoprostol is a prostaglandin E 1 analogue that reduces the incidence of nonsteroidal antiinflammatory drug-induced gastric injury. The main side effects of misoprostol therapy are abdominal discomfort, cramping, and diarrhea. Studies in dogs suggest that prostaglandins may initiate a giant migrating complex pattern and increase colonic propulsive activity. 39 In vitro studies of misoprostol show that it stimulates feline and canine colonic smooth muscle contraction. 40 Given its limited toxicity, misoprostol may be useful in cats (and dogs) with severe refractory constipation.

Ranitidine and nizatidine, classic histamine H 2 receptor antagonists, may also stimulate canine and feline colonic motility. These drugs stimulate contraction apparently through inhibition of tissue acetylcholinesterase and accumulation of acetylcholine at the motor endplate. It is not yet clear how effective these drugs are in vivo, although both drugs stimulate feline colonic smooth muscle contraction in vitro. 41 Cimetidine and famotidine, members of the same classification of drug, are without this effect.

Colectomy should be considered in cats that are refractory to medical therapy. Cats have a generally favorable prognosis for recovery following colectomy, although mild to moderate diarrhea may persist for weeks to months postoperatively in some cases. 42, 43 Pelvic osteotomy without colectomy has been recommended for cats with pelvic fracture malunion and hypertrophic megacolon of less than 6 months duration. 44 Symphyseal distraction-osteotomy with spirally fashioned orthopedic wire has also been used in the surgical management of this disorder. 45 Pathologic hypertrophy may be reversible with early pelvic or symphyseal distraction osteotomy in such cases. Some surgeons still prefer colectomy in this instance because of the technical difficulty of some pelvic osteotomies. 46 Subtotal colectomy is an effective treatment for feline idiopathic megacolon or megacolon secondary to the mechanical obstruction created by old, healed pelvic fractures. Recommendations for removal of the ileocolic valve and ileum vary in cats with megacolon. The ileocolic blood vessels tether the distal ileum and proximal ascending colon, preventing anastomosis to the distal colon; thus if a complete colectomy is performed, these vessels must be sacrificed. This necessitates removing the ileum, which has important normal functions in water, vitamin B 12 , and bile salt resorption, and performing a jejunocolic anastomosis. In spite of this concern, postoperative intestinal function was normal in four cats evaluated after subtotal colectomy and jejunocolic anastomosis. 43, 47 The ileocolic valve also minimizes colonic bacterial access to the small intestine, 44 so preservation of the valve would be ideal to minimize small intestinal bacterial overgrowth and deconjugation of bile salts. However, preservation of the ileocolic junction necessitates leaving several centimeters of the ascending colon to ensure a tension-free anastomosis, possibly predisposing these cats to recurrent constipation. To evaluate these concerns, cats with megacolon treated with colectomy were studied retrospectively. Cats with excision of the ileocolic junction had significantly looser stool on long-term followup. 43 However there was no difference in the incidence of constipation between cats with preservation versus excision of the ileocolic junction. 48 This is perhaps explained by in vitro experiments with ascending and descending colonic smooth muscle from cats with clinical megacolon showing that smooth muscle dysfunction is less severe in the ascending colon. 8 When the ileocolic junction is preserved, the ascending colon is transected approximately 3 cm distal to the ileocolic junction to ensure a tension-free anastomosis. An end-to-end colocolostomy is performed using single interrupted sutures of 4-0 polydioxanone. 47 The successful use of a biofragmentable anastomosis ring has also been reported. 46 The omentum is wrapped around the anastomotic site and the abdomen is thoroughly lavaged with a warm, balanced electrolyte solution. All lavage fluid is aspirated from the peritoneal cavity before the incision is closed.

Cats recovering from colectomy are maintained on intravenous fluids until they commence eating and drinking. Electrolytes are supplemented if necessary. Bowel movements may be soft or loose and more frequent than normal. A highly digestible, low-residue diet is fed. In cats with profuse postoperative diarrhea in which small intestinal bacterial overgrowth is suspected, a short course of antibiotics is administered.

Many cats have one or two episodes of constipation without further recurrence, although others may progress to complete colonic failure. Cats with mild to moderate constipation generally respond to conservative medical management (e.g., dietary modification, emollient or hyperosmotic laxatives, colonic prokinetic agents). Early use of colonic prokinetic agents (in addition to one or more laxative agents) is likely to prevent the progression of constipation to obstipation and dilated megacolon in these cats. Some cats may become refractory to these therapies, however, as they progress through moderate or recurrent constipation to obstipation and dilated megacolon. These cats eventually require colectomy. Cats have a generally favorable prognosis for recovery following colectomy, although mild to moderate diarrhea may persist for 4 to 6 weeks postoperatively in some cases.

IBS is a human chronic gastrointestinal tract disorder of unknown origin that is characterized by abdominal pain and altered bowel habits in the absence of detectable biochemical or structural abnormalities. 49 IBS is one of the most common functional GI disorders with an estimated prevalence of 10% to 15% in Western adult populations. Direct and indirect costs of IBS reach up to $30 billion per year in the United States alone. 49 IBS is commonly subdivided into different phenotypes depending upon the most prevalent bowel habit: diarrhea-predominant IBS (IBS-D), constipation-predominant IBS (IBS-C), and mixed features IBS (IBS-M). 50 Because of the inability of animal species to describe clinical symptoms such as abdominal pain and discomfort, IBS is not a very-well-defined syndrome in veterinary medicine. Nonetheless, recurring vomiting and diarrheal disorders are seen in companion animal species that are unaccompanied by mucosal morphologic change, and are presumed therefore to be of functional or physiological origin. 51 The reader is referred to Chapter 41 for a more detailed discussion of IBS and its management.

A fiber-responsive large bowel diarrheal syndrome similar to IBS in humans has been characterized in dogs. 51 Affected animals have a chronic idiopathic large bowel-type diarrhea characterized by excessive fecal mucus, hematochezia, and tenesmus. Abdominal pain and weight loss are occasionally reported by pet owners. Multiple diet changes and empirical medications fail to relieve clinical signs. Medical investigation is negative for bacterial and other pathogen infections, colitis, and colonic neoplasia, and the term chronic large bowel diarrhea is applied to the patient's disorder. Dogs

Alimentary lymphoma is less common in dogs than in cats, representing only 7% of all canine lymphomas. 19 Lymphoma is the most common malignancy in cats, and the GI tract is the most common predilection site for this tumor. Feline alimentary lymphoma may affect any component of the digestive system (stomach, intestine, colon, liver, biliary tract, and pancreas), but it most commonly involves the small intestine. [19] [20] [21] [22] [23] [24] [25] Lymphoma can be classified histologically into small cell (lymphocytic; low grade; well differentiated) or large cell (lymphoblastic; high grade; undifferentiated) types. 19 Low-grade lymphocytic lymphoma has a higher reported incidence than high-grade lymphoblastic lymphoma in most case series. [20] [21] [22] [23] [24] [25] Large granular lymphoma is a subtype that is characterized by the presence of natural killer T lymphocytes with intracytoplasmic granules. Clinically, these types of lymphoma are distinct entities with different clinical presentations, therapies, and outcomes. 19 Although infection with FeLV and FIV are major risk factors for the development of feline lymphoma, cats with GI lymphoma are usually serologically negative for both infections. 19 Feline gastrointestinal lymphoma has been associated with Helicobacter infection 26 and exposure to household cigarette smoke. 27

Mechanical obstruction is the most common pathophysiologic consequence of locally invasive colonic tumor. Other nonneoplastic processes such as intussusception, FIP granuloma, fibrosing stricture, linear and nonlinear foreign bodies, hematoma, and phycomycosis lesions also cause intraluminal obstruction. Prolonged obstruction induces smooth muscle hypertrophy proximal to the site of the obstruction. 28 Other pathophysiologic consequences of intestinal obstruction are pronounced fluid secretion and malabsorption of water and solutes; fluid, electrolyte, and acid-base disturbances; proliferation and translocation of luminal bacteria; and inflammation, devitalization, and perhaps even perforation of the colon. Secretory diarrheas have been reported with carcinoids of the rectum, colon, and intestine.

Most affected dogs have signs of hematochezia, mucoid feces, tenesmus, and dyschezia of varying severity. Importantly, the clinical signs observed with colorectal neoplasia are often indistinguishable from other causes of obstruction or chronic colitis. Hematochezia is infrequently reported with leiomyosarcomas or leiomyomas presumably because these tumors do not typically involve the mucosa. Other clinical signs depend on the tumor type and location. Vomiting, malabsorption, and cachexia may be observed, for example, when multifocal or diffuse tumors (e.g., lymphosarcoma) involve the proximal portions of the gastrointestinal tract. Gastrointestinal stromal tumors, particularly the leiomyomas, have been associated with hypoglycemia and the resulting clinical signs of muscular weakness and seizure activity. 29 Functional plasmacytomas secrete a single class of immunoglobulin and affected animals may go on to develop hyperviscosity syndrome, for example, retinal bleeding and epistaxis. If colonic perforation has occurred, animals may be presented moribund with fever, lethargy, anorexia, vomiting, abdominal pain, and collapse.

Vomiting (65%), diarrhea (52%), and weight loss (46%) are common clinical signs in cats with colonic neoplasia. 16 Most cats with colonic (and alimentary) lymphosarcoma are FeLVnegative. These lymphomas are still believed to be caused by FeLV, affected with this syndrome may respond to the feeding of a highly digestible diet that is supplemented with soluble fiber. 51 The reader is referred to Chapter 41 for more detailed discussion of IBS and its management.

In dogs, tumors of the large intestine are more common than tumors of the stomach and small intestine. The mean age of dogs affected with colonic neoplasia is variably reported between 7 and 11 years of age. 1 Most colonic tumors of dogs are malignant and include the adenocarcinomas, lymphosarcomas, and gastrointestinal stromal tumors (Table 58-10) . Other reported tumors include leiomyosarcoma, neurofibrosarcoma, fibrosarcoma, and ganglioneuroma. [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] Leiomyosarcomas are the most common (91%) of the gastrointestinal stromal tumors. [12] [13] [14] [15] Most colonic neoplasia develop in the descending colon and rectum, although leiomyosarcomas more frequently develop in the cecum. 4, 6 Local tumor invasion apparently occurs at a slower rate with canine colonic neoplasia, and metastasis to distant sites is relatively uncommon. Benign colonic neoplasia (e.g., adenomas, adenomatous polyps, and leiomyomas) also occur, although they are less common than malignant tumors. Malignant transformation of adenomatous polyps to carcinoma in situ and invasive adenocarcinoma has been demonstrated in the dog just as it has in humans. 1, 16, 17 Extramedullary plasmacytomas are uncommon tumors of the gastrointestinal tract, but many of these occur in the large intestine and rectum. 12, 13 All of the aforementioned tumors are associated with signs of inflammation and obstruction (e.g., hematochezia, tenesmus, and dyschezia). Carcinoids (rare 5-hydroxytryptamine [5-HT] secreting tumors) are occasionally associated with diarrhea because of the effects of 5-HT on secretion and motility.

In cats, adenocarcinoma (46%) is the most common tumor of the large intestine (see Table 58 -10), followed by lymphosarcoma (41%) and mast cell tumors (9%). 14, 15, 18 The mean age of cats affected with colonic neoplasia is 12.5 years. The descending colon (39%) and the ileocolic sphincter (28%) are the most common sites of colonic neoplasia in the cat. Unlike colonic tumors in the dog, feline colonic tumors have a high rate (63%) of metastasis and, of course, metastasis is associated with decreased survival time. Metastatic sites include colonic lymph nodes, mesenteric lymph nodes, liver, spleen, bladder, urethra, omentum, mesocolon, lungs, duodenum, and peritoneum. with integrated virus causing neoplastic transformation in the absence of viral replication. Although most lymphomas in cats appear to be comprised of malignant T lymphocytes, most colonic (and alimentary) lymphomas are of B-cell origin. Alimentary and colonic lymphomas originate primarily from submucosal lymphocytes and/or mucosal lymphoid follicles, although two studies reported an epitheliotropic form of T-cell intestinal lymphomas. 30, 31 Epitheliotropic T-cell lymphomas have not yet been reported in the feline colon. Feline lymphocytic lymphoma is typically a slowly progressive disease with a protracted history, whereas lymphoblastic lymphoma is more often characterized by an acute onset ( 

Canine rectal adenocarcinomas are palpable in 60% to 80% of clinical cases, but colonic and cecal lesions are not as readily apparent on physical examination. 1, 13, 28, 32, 33 More than 50% of cats with colonic masses have a palpable abdominal mass. 16 Survey and contrast radiographic and ultrasonographic studies have been employed with varying levels of success in the diagnosis of canine and feline colonic neoplasia. Annular stenotic lesions associated with adenocarcinoma of the colon may manifest as proximal colonic dilation on survey radiographs. Radiographic contrast material more precisely outlines the narrowing of the lumen at the site of the tumor. Although still of some clinical utility, contrast studies have been largely superseded by ultrasonography and other imaging modalities. Ultrasonography is presently considered to be the most effective means of diagnosing colonic tumors in dogs and cats and appears to be useful in evaluating mural lesions and associated abdominal changes such as lymphadenopathy (Figure 58-16) . 33 Ultrasonography was reported to be useful 84% of the time in localizing feline colonic neoplasia in one study. 16 Ultrasonographic features of colonic tumors include transmural wall thickening with complete loss of the normal wall layering, fluid accumulation proximal to the lesion, and reduced regional motility. 33 Transabdominal fine-needle aspiration, peritoneal fluid cytology, and endoscopic exfoliative cytology may be useful in the diagnosis of lymphoma, but histopathology is generally required for a definitive diagnosis of other colonic neoplasia. CT and MRI scanning have not been sufficiently evaluated for reasonable comparisons to be made with ultrasonography. Flexible colonoscopy with mucosal biopsy is the preferred method of diagnosis for colonic neoplasia. Endoscopic abnormalities may include mass effect, mucosal bleeding, increased mucosal friability, erosions and ulcers, and circumferential luminal narrowing with submucosal infiltrative lesions. Multiple biopsy specimens should always be taken from diseased tissue, adjacent healthy tissue, as well as the transition zone between healthy and diseased tissue. With tumor necrosis, the pathologist has a much better chance of diagnosing and staging the disease by evaluating nonnecrotic tissue.

The treatment of colonic neoplasia will depend upon tumor type, anatomic location, and presence and extent of metastases (Box 58-2; see Tables 58-12 and 58-13). Complete surgical excision is the recommended therapy for focal adenocarcinomas, cecal leiomyosarcomas, and obstructive lymphomas. Multiagent chemotherapy (prednisone, vincristine, cyclophosphamide) has been used to treat colonic lymphoma, but it does not appear to alter survival time in affected cats. 16 Cyclooxygenase (COX)-2 upregulation may contribute to the growth characteristics of some canine colonic neoplasia. [34] [35] [36] Consequently, selective COX-2 inhibitors (e.g., piroxicam, meloxicam) may be useful in the treatment of some canine colonic neoplasia. Plasmacytomas may be managed with adjuvant chemotherapy (e.g., prednisone and melphalan) following surgical excision. Radiation therapy has been used to palliate recurrent adenocarcinomas with varying results and complications; however, postradiation peritonitis and perforation have been reported in some cases. 37

In dogs with rectal or colonic tumors, appropriate staging is vital to determine the extent of local and systemic disease. In many cases, a careful digital rectal examination can delineate the extent of local disease in the rectum and provide subjective information on the enlargement of regional lymph nodes. Thoracic radiographs are Adequate nutrition is vital for dogs and cats recovering from large intestinal surgery. Early feeding increases anastomosis strength and promotes enteric epithelial proliferation and function. 46, 47 Ideally, the diet should provide a source of soluble fiber which, when hydrolyzed to short-chain fatty acids, stimulates colonic mucosal proliferation. 46 In animals with fecal continence difficulties after extensive rectal resection, a low-residue diet is fed twice daily. The animal is then walked for 20 to 30 minutes after eating. In many cases, the gastrocolic reflex will result in defecation and near complete emptying of the colon during this time, minimizing subsequent fecal soiling in the house.

The prognosis for adenomatous polyps, leiomyomas, and fibromas is generally favorable. Adenocarcinomas, lymphosarcomas, and plasmacytomas tend to recur and/or metastasize to distant sites. Dogs with annular colorectal adenocarcinomas have a particularly poor prognosis with a mean survival time of only 1.6 months. 1, 32 The prognosis for most malignant tumors is generally guarded. Surgical resection alone results in 22 month (dogs) and 15 month (cats) average survival times in dogs and cats. 1, 16 It should be noted that cats undergoing subtotal colectomy for colonic adenocarcinoma had a longer survival time than those receiving mass resection only (median survival time of 138 days versus 68 days). 16 Not surprisingly, cats with metastatic lesions had much shorter survival times, 49 days versus 259 days. 16 

Colonic ulcers may develop following glucocorticoid therapy and neurosurgery in dogs with spinal cord injury. Gastric ulcers are of greater prevalence in this circumstance, but colonic ulcers may be equally devastating. [1] [2] [3] [4] Affected dogs were most often Dachshunds with thoracolumbar disk disease treated with decompressive surgery and dexamethasone at doses of 0.25 to 4.4 mg/kg/day. Colonic ulcer is not a frequent complication of either intervertebral disk disease or corticosteroid therapy. In the initial report of the condition, colonic perforation was described in two dogs out of "several thousand." 1 Ten additional cases were subsequently reported until 1986, 2-4 and since then no additional reports have been published. This may represent increased awareness of the condition, reluctance to publish on a previously described condition, or perhaps a shift away from the use of dexamethasone in dogs with intervertebral disk disease. Colonic perforation is infrequent in humans treated with corticosteroids for neurologic disease 5 but may occur more commonly when dexamethasone is used. 6 In nonneurologic conditions, the frequency of perforation is influenced by the underlying disease and the presence of a diverticulum in the sigmoid colon. 7 Why this lesion develops in some dogs but not others is not readily explained. made to rule out pulmonary metastatic disease. Abdominal ultrasonography is used to rule out abdominal metastatic disease and to guide aspiration and biopsy of enlarged iliac lymph nodes. Proctoscopy and colonoscopy often reveal the local extent of neoplastic disease. It is vital that colonoscopy be continued oral to rectal tumors as additional neoplasms are reported in the colon in a percentage of these cases. 38, 39 Mechanical cleansing is recommended before surgery of the large intestine in human, although preoperative enemas are contraindicated in cases of suspected large intestinal perforation. Perioperative antibiotics are administered to minimize the chance of surgical infection. Randomized, controlled clinical trials of antimicrobial prophylaxis in canine and feline colonic surgery have not been conducted, but based on human trials, 40 antibiotics effective against aerobes, especially the anaerobes that predominate in the large intestine, are administered intravenously once at the beginning of surgery. Antibiotics are not administered again unless either there is contamination at surgery or the procedure takes longer than 2 hours. In the latter case a second intravenous dose of antibiotics is administered. Antibiotics are continued postoperatively in cases with preoperative or surgical contamination based on the results of operative culture and sensitivity testing.

In animals requiring surgery for cecal or colonic disease, a ventral midline laparotomy is performed. After conducting a thorough abdominal exploration for concurrent or metastatic disease, the affected area of the large intestine is packed off with moistened laparotomy sponges. Resection of the cecum can be performed with or without preservation of the ileocolic junction, depending on the extent of the local disease. In most cases of cecal neoplasia a complete resection and jejuno-or ileocolonic anastomosis is performed to ensure adequate tumor resection.

Various techniques and surgical approaches have been described for removal of rectal tumors. 39 The approach and technique vary with the extent and location of the mass(es). Tumors in the proximal rectum may be accessed by a ventral midline laparotomy combined with a pelvic osteotomy. Healing of the distal colon and/or proximal rectum is complicated by the poor blood supply to this area of the large intestine. 41 A dorsal approach has been described for tumors involving the middle third of the rectum 39, 42 ; however, many tumors in this area are also amenable to resection via a rectal pull-through. 39, 43 The plexus of pelvic nerves at the peritoneal reflection is vital to postoperative fecal continence. In an experimental study on healthy dogs, both transection alone and resection of 4 cm of rectum via a dorsal approach resulted in fecally continent dogs. Resection of 6 cm of the rectum, including the peritoneal reflection, caused fecal incontinence. 42 This limitation on resection is problematic in animals with larger rectal tumors, as a 2-cm gross margin is recommended on both sides of the tumor. 39, 44, 45 

Postoperative treatment depends largely on the underlying reason for cecal, colonic, or rectal surgery. Pre-or postoperative epidural anesthesia using a combination of local anesthetic and narcotic provides effective pain relief. Animals receiving epidural anesthesia may not be able to urinate normally for 12 to 24 hours, hence bladder size must be evaluated frequently and the bladder gently expressed or catheterized if needed. Narcotics, narcotic agonists/ antagonists, partial µ-agonists, and COX-2 inhibitory class nonsteroidal antiinflammatory drugs are alternatives for pain management in dogs. Narcotic agonists/antagonists are effective in cats. is anastomosed. The abdominal cavity is thoroughly lavaged with warm balanced electrolyte solution. All of the lavage fluid and associated peritoneal contaminants are aspirated. Depending on the degree of residual peritoneal contamination, the abdomen is either closed, closed after placement of closed suction drains, or left open to facilitate drainage and covered with a sterile bandage.

Colonic ulcer and perforation is generally associated with a poor prognosis. A preventive approach to this complication appears to be warranted in high-risk patients: (a) use of less-potent glucocorticoids (e.g., prednisone or prednisolone) instead of dexamethasone, and (b) limited or no use of glucocorticoids.

Etiology HUC was first reported by Van Kruiningen in a kennel of Boxer dogs in 1965. 13 A number of other cases have been reported since then, and a similar disease process has been reported in the French Bulldog. The pathognomonic lesion of this disease is a mucosal infiltration with large numbers of macrophages staining positively with PAS, and accompanied by mucosal ulceration and loss of goblet cells. 14 Although the term histiocytic ulcerative colitis describes many features of the disease, it understates the mixed lymphocytic plasmacytic component of the inflammation, and the term granuloma tous colitis has been adopted to more completely characterize the histopathology. For the most part, the disease is localized to the large intestine and regional lymph nodes; however, in some instances PAS-positive macrophages may be found in lymph nodes remote from the intestine, suggesting that there is limited systemic distribution of the disease. Historically, an infectious etiology had been speculated but never proved. At least two independent lines of investigation now point to an adherent and invasive E. coli as the underlying etiology of granulomatous colitis. 14, 15 The pathophysiology, clinical examination, diagnosis, and therapy of granulomatous colitis of Boxer dogs and other breeds are discussed in the "Inflammation" section.

There are many factors that probably interact to cause colonic perforation in this cohort of dogs. Spinal cord injury and sympathetic nerve stimulation associated with pain likely slow colonic transit and increase fecal retention. It is also likely that immobility and pain associated with abdominal muscle contraction inhibit voluntary defecation in dogs with intervertebral disk disease. This leads to fecal retention and colonic distention. In humans, it is postulated that prolonged increases in colonic intraluminal pressure lead to mucosal ischemia resulting in progressive necrosis, ulceration, and perforation. 6 The effects of corticosteroids have not been extensively studied in the colon and are largely extrapolated from information gained in gastric studies. 8 Corticosteroids are presumed to decrease colonic mucus production, alter the composition of colonic mucus, and decrease mucosal repair in the colon, leading to perturbations in the colonic mucosal barrier. 3 These effects are thought to be secondary to depletion of local prostaglandin production. In addition, glucocorticoids inhibit the expression of inducible nitric oxide synthase in vascular endothelial cells, 9 perhaps further affecting colonic blood supply. 10 Together, these factors coalesce to induce erosion of the colonic mucosa, colonic perforation, and peritonitis. 3 The relationship between intervertebral disk disease, corticosteroid treatment, and colonic perforation is highlighted by a report describing 29 dogs with gastrointestinal perforation associated with administration of a COX-2 inhibitor. None of the latter dogs were treated for intervertebral disk disease, and none of the perforations were in the colon. 11 The left colic flexure or proximal portion of the descending colon appears to be at greatest risk for colonic ulceration and perforation; two-thirds of the published cases were reported at this site. 3, 4 Nonambulatory neurosurgical patients treated with dexamethasone are at greatest risk for development of colonic perforation. Colonic perforation is often preceded by variable nonspecific signs, most frequently depression, anorexia, and emesis. Perforation appears to be associated with 100% mortality, emphasizing the importance of prevention and early clinical recognition.

Middle aged, male dogs are most often affected, usually within 5 to 7 days of surgery. Depression, anorexia, emesis, abdominal pain, constipation, melena, and fever are the most important clinical signs. Many of these signs are subtle and easily missed by some pet owners. The immunosuppressive properties of glucocorticoids may mask the initial signs of peritonitis associated with colonic perforation.

If suspected, patients at risk should be carefully evaluated for perforation and peritonitis. Imaging studies (radiography and ultrasonography), abdominocentesis, peritoneal lavage, and exploratory surgery, if indicated, should be considered in patients at risk. A diagnosis of peritonitis is made from cytologic evaluation of peritoneal fluid or measurements comparing glucose, pH, and lactate concentrations in peripheral blood and peritoneal fluid. 12 The perforations most often occur on the antimesenteric surface of the proximal descending colon. 3

Treatment involves rapid circulatory resuscitation with crystalloids and colloids, administering broad-spectrum bactericidal antibiotics, and emergency laparotomy. The perforation of the colon is identified, the affected area of bowel is resected, and the remaining colon 

A gross and microscopical morphometric evaluation of feline large intestinal anatomy

Miller's Anatomy of the Dog

A morphometric study of the canine colon: comparison of control dogs and cases of colonic disease

Endocrine cell populations in the colon and rectum of cat, dog, and monkey: fine structure, immunocytochemistry, and distribution

Analysis of leucocyte subsets in the canine intestine

Immunohistochemical characterization of immunoglobulin-containing cells and T cells in the colonic mucosa of healthy dogs

Flow cytometric analysis of colonic and small intestinal lymphocytes obtained by endoscopic biopsy in the healthy dog

The gastrointestinal tract and adverse reactions to food

A scoring index for disease activity in canine inflammatory bowel disease

Idiopathic inflammatory bowel disease in dogs and cats

Constipation, obstipation, and megacolon

Opportunistic infections associated with retroviral infections in cats

Enteropathogenic bacteria and dogs and cats

Distributions of interstitial cells of Cajal in stomach and colon of cat, dog, ferret, opossum, rat, guinea pig and rabbit

Spontaneous electrical activity of interstitial cells of Cajal isolated from canine proximal colon

Identification and classification of interstitial cells in the canine proximal colon by ultrastructure and immunocytochemistry

Endoscopic biopsy interpretation in canine or feline enterocolitis

Age-related changes in mechanical properties of cat circular intestinal muscle

Effect of commercial diets on the endoscopic and histologic appearance of the colon of normal dogs

Nutritional impact on the canine colonic microstructure and function

Protein source and their effects upon canine colonic morphology and mucosal energetics

Cellulose, beet pulp, and pectin/gum arabic effects on canine colonic microstructure and histopathology

Gastrointestinal mucus

Chronic diarrhea in the dog

Heterogeneity of intestinal transport

Colonic fluid and electrolyte transport in health and disease

Electrolyte transport in the mammalian colon

Evaluation of B and T lymphocytes and plasma cells in colonic mucosa from healthy dogs and from dogs with inflammatory bowel disease

Plasma cell populations in the colonic mucosa of clinically normal dogs

Van der Gaag I: The histologic appearance of large intestinal biopsies in dogs with clinical signs of large bowel disease

Number and distribution of IgM cells and IgA cells in colonic tissue of conditioned sex-and breed-matched dogs

Chronic intestinal inflammation and intestinal disease in dogs

Diseases of the small intestine

The distribution of lymphocytes expressing αβ and γδ T-cell receptors, and the expression of mucosal addressin cell adhesion molecule-1 in the canine intestine

Quantitative measurement of feline colonic transit

Colonic migrating and nonmigrating motor complexes in dogs

Giant migrating contractions during defecation in the dog colon

Colonic lymphocyte and plasma cell populations in dogs with lymphocytic-plasmacytic colitis

Evaluation of Th1, Th2 and immunosuppressive cytokine mRNA expression within the colonic mucosa of dogs with idiopathic lymphocytic-plasmacytic colitis

Cytokine mRNA quantification in duodenal mucosa from dogs with chronic enteropathies by real-time reverse transcriptase polymerase chain reaction

Measurement of cytokine mRNA expression in intestinal biopsies of cats with inflammatory enteropathy using quantitative real-time RT-PCR

The relationship of mucosal bacteria to duodenal histopathology, cytokine mRNA, and clinical disease activity in cats with inflammatory bowel disease

Food allergies and food intolerances

Gastrointestinal aspects of food allergy: A review

The canine model of dietary hypersensitivity

Pathogenesis of diarrhea in ulcerative colitis: new views on an old problem

Colonic motor activity

Colonic motor activity in acute colitis in conscious dogs

Inflammatory modulation of calciumactivated potassium channels in canine colonic circular smooth muscle cells

Impairment of Ca(2+) mobilization in circular muscle cells of the inflamed colon

Down-regulation of L-type calcium channels in inflamed circular smooth muscle cells of the canine colon

Selective modulation of PKC isozymes by inflammation in canine colonic circular muscle cells

Inflammation inhibits muscarinic signaling in in vivo canine colonic circular smooth muscle cells

NF-kappa B activation by oxidative stress and inflammation suppresses contractility in colonic circular smooth muscle cells

Chronic enteropathies in dogs: evaluation of risk factors for negative outcome

Lymphocytic-plasmacytic colitis in the cat

Lymphocytic/plasmacytic colitis in cats: 14 cases (1985-1990)

Treatment of chronic idiopathic large-bowel diarrhea in dogs with a highly digestible diet and soluble fiber: a retrospective review of 37 cases

Evaluation of disease activity markers in dogs with idiopathic inflammatory bowel disease

Perinuclear antineutrophilic cytoplasmic antibody and response to treatment in diarrheic dogs with food responsive disease or inflammatory bowel disease

Update on molecular techniques for diagnostic testing of infectious disease

Cytologic examination of exfoliative specimens obtained during endoscopy for diagnosis of gastrointestinal disease in dogs and cats

Ultrasonography of the normal canine gastrointestinal tract

Ultrasonographic evaluation of gastrointestinal diseases in dogs and cats

Subtraction CT colonography: feasibility in an animal model

Evaluation of a colonic lavage solution to prepare the colon of the dog for colonoscopy

Comparison of an orally administered gastrointestinal lavage solution with traditional enema administration as preparation for colonoscopy in dogs

Effect of liquid perfusion and cleansing on canine colonic motor activity

Endoscopic, biopsy, and histopathologic guidelines for the evaluation of gastrointestinal inflammation in dogs and acts

Mechanisms of disease: pathogenesis of Crohn's disease and ulcerative colitis

Bacterial-mucosal interactions in inflammatory bowel disease: an alliance gone bad

Bacterial interactions with cells of the intestinal mucosa: Toll-like receptors and NOD2

TLR signaling in the gut in health and disease

Expression and function of TLR2, TLR4, and Nod2 in primary canine colonic epithelial cells

Upregulation of toll-like receptors in chronic enteropathies in dogs

Differential expression of Toll-like receptor 2 and 4 in duodenal biopsies from dogs with inflammatory bowel disease predicts severity of disease

Evaluation of mucosal bacteria and histopathology, clinical disease activity and expression of Toll-like receptors in German shepherd dogs with chronic enteropathies

Polymorphisms in the TLR4 and TLR5 gene are significantly associated with inflammatory bowel disease in German shepherd dogs

Immunohistological study of IgA, IgG and IgM in endoscopic biopsies of dogs with plasmacytic-lymphocytic colitis

Evaluation of B and T lymphocytes and plasma cells in colonic mucosa from healthy dogs and from dogs with inflammatory bowel disease

Antibiotic-responsive histiocytic ulcerative colitis in 9 dogs

Histiocytic ulcerative colitis in a Boxer dog

Canine histiocytic ulcerative colitis

Histiocytic ulcerative colitis in the boxer dog in the UK

An immunohistochemical study of histiocytic ulcerative colitis in boxer dogs

Histiocytic ulcerative colitis in three non-boxer dogs

Histiocytic ulcerative colitis in a French Bulldog

Feline histiocytic colitis. A case report with electron microscopy

The ultrastructure of macrophages in granulomatous colitis of boxer dogs

Adherent and invasive Escherichia coli is associated with granulomatous colitis in boxer dogs

The comparative importance of E. coli antigen in granulomatous colitis of Boxer dogs

High prevalence of adherent-invasive Escherichia coli associated with ileal mucosa in Crohn's disease

Escherichia coli isolated from a Crohn's disease patient adheres, invades, and induces inflammatory responses in polarized intestinal epithelial cells

The Crohn's diseaseassociated adherent-invasive Escherichia coli strain LF82 replicates in mature phagolysosomes within J774 macrophages

Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease

Mucosal interplay among commensal and pathogenic bacteria: lessons from flagellin and Toll-like receptor 5

CARD15 variants determine a disturbed early response of monocytes to adherent-invasive Esch erichia coli strain LF82 in Crohn's disease

Granulomatous colitis of Boxer dogs: comparative aspects

The ultrastructure of macrophages in granulomatous colitis of Boxer dogs

Canine histiocytic ulcerative colitis. A condition resembling Whipple's disease, colonic histiocytosis, and malakoplakia in man

Granulomatous colitis of boxer dogs

Antimicrobial resistance impacts clinical outcome of granulomatous colitis in boxer dogs

Canine histiocytic ulcerative colitis

E. coli associated with granulomatous colitis of Boxer dogs frequently manifest resistance to antibiotics

Association of perianal fistula and colitis in the German shepherd dog: response to

Optimal fecal assessment

Complications associated with 355 flexible colonoscopic procedures in dogs

Histopathological standards for the diagnosis of gastrointestinal inflammation in endoscopic biopsy samples from the dog and cat: a report from the World Small Animal Veterinary Association Gastrointestinal Standardization Group

Interobserver variation among histopathologic evaluations of intestinal tissues from dogs and cats

Chronic colitis in dogs

Nutritional management of idiopathic chronic colitis in the dog

Use of a restricted antigen diet in the management of idiopathic canine colitis

National Research Council: Carbohydrates and fiber

Effect of dietary supplementation with fructo-oligosaccharides on fecal flora of healthy cats

Effects of probiotic bacteria in dogs with food responsive diarrhoea treated with an elimination diet

Cytokine expression in an ex vivo culture system of duodenal samples from dogs with chronic enteropathies: modulation by probiotic bacteria

Pharm profile: Metronidazole. Compend Contin Educ Pract Vet

Review article: mode of action and delivery of 5-aminosalicylic acid-new evidence

Nuclear receptor and nuclear receptor target gene messenger ribonucleic acid levels at different sites of the gastrointestinal tract and in liver of healthy dogs

Nuclear receptor and target gene mRNA abundance in duodenum and colon of dogs with chronic enteropathies

Keratoconjunctivitis sicca in the dog following 5-aminosalicylic acid administration

Clinical Immunology of the Dog and Cat

Pharmacokinetics and clinical efficacy of cyclosporine treatment of dogs with steroidrefractory inflammatory bowel disease

Canine inflammatory bowel disease: retrospective analysis of diagnosis and outcome in 80 cases

A granulomatous colitis of dogs with histologic resemblance to Whipple's disease

Colitis of boxer dogs

Canine histiocytic ulcerative colitis. An ultrastructural study of the early mucosal lesion

Efficacy of milbemycin oxime against naturally acquired or experimentally induced Ancylostoma spp and Trichuris vulpis infections in dogs

The prevalence of Balantidium coli infection in fifty-six mammalian species

Severe chronic canine diarrhea associated with BalantidiumTrichuris infection

The dog, Canis familiaris, a new host of Balantidium sp

Canine helminthiasis complicated with Bal antidium species

Balantidium infection in the dog

Canine balantidiasis-its treatment, epidemiological and zoonotic significance

Cerebral mass in a puppy

Systemic amebiasis with distemper in a dog

Enteric protozoal infections

Tritrichomonas foetus and not Pentatrichomonas hominis is the etiologic agent of feline trichomonal diarrhea

Prevalence of and risk factors for feline Tritrichomonas foetus and giardia infection

Experimental infection of cats with Tritrichomonas foetus

Histologic features associated with Tritricho monas foetus-induced colitis in domestic cats

Use of a commercially available culture system for diagnosis of Tritrichomonas foetus infection in cats

Single-tube nested PCR for detection of Tritrichomonas foetus in feline feces

Efficacy of ronidazole for treatment of feline Tritrichomonas foetus infection

Outcome of cats with diarrhea and Tritrichomonas foetus infection

Infectious Dis eases of the Dog and Cat

Disseminated histoplasmosis in dogs: 12 cases (1981-1986)

Disseminated histoplasmosis in cats: 12 cases (1981-1986)

Itraconazole for the treatment of histoplasmosis in cats

Update on canine and feline fungal diseases

Diseases of the large intestine

Gastrointestinal phycomycosis in 63 dogs

Gastrointestinal pythiosis in Missouri dogs: eleven cases

Association between anal furunculosis and colitis in the dog: preliminary observations

Pattern-recognition receptor mRNA expression and function in canine monocyte/macrophages and relevance to canine anal furunuclosis

Analysis of NOD1, NOD2, TLR1, TLR2, TLR4, TLR5, TLR6 and TLR9 genes in anal furunculosis of German Shepherd dogs

Risk of anal furunculosis in German Shepherd dogs is associated with the major histocompatibility complex

Long-term evaluation of canine perianal fistula disease treated with exclusive fish and potato diet and surgical excision

Evidence-based veterinary dermatology: a systematic review of the pharmacotherapy of canine atopic dermatitis

Regional eosinophilic coloproctitis, typhlitis and ileitis in a dog

Caecal impaction and chronic intestinal pseudo-obstruction in a dog

Caecal impaction in a dog

Hypercalcemia in a dog: a challenging case

Heterobilharzia americana infection in a dog

Heterobilharzia infection in the dog and other mammals in Louisiana

Heterobilharzia Americana Infection in a Dog

Elevated parathyroid hormone-related protein and hypercalcemia in two dogs with schistosomiasis

Miracidia hatching technique for diagnosis of canine schistosomiasis

Fenbendazole for the treatment of Hetero bilharzia americana infection in dogs

Strongyloides tumefaciens infection in a cat

Strongyloides tumefaciens in cats

Multiple adenomata of the large intestine of a cat caused by a species of Strongyloides

Whipworms and intestinal threadworms

The whipworm as a blood sucker

Trichuris and other trichinelloid nematodes of dogs and cats in the United States

Basal and ACTH-stimulated plasma aldosterone concentrations are normal or increased in dogs with trichuriasis-associated pseudohypoadrenocorticism

Outbreak of Clostridium difficile-associated disease in a small animal veterinary teaching hospital

The roles of Clostridium difficile and enterotoxigenic Clostridium perfringens in diarrhea in dogs

Genotypic and phenotypic characterization of Clostridium perfringens and Clostridium difficile in diarrheic and healthy dogs

Intestinal carriage of Clos tridium difficile in neonate dogs

Suspected Clostridium difficile-associated diarrhea in two cats

Bacterial-associated diarrhea in the dog: a critical appraisal

Antimicrobial susceptibilities of canine Clos tridium difficile and Clostridium perfringens isolates to commonly utilized antimicrobial drugs

Multiplex polymerase chain reaction assay for genotyping Clostridium perfringens

The enteric toxins of Clostridium perfringens

Use of dogs as an assay for Clostridium perfringens enterotoxin

Evaluation of methods to diagnose Clostridium perfringens-associated diarrhea in dogs

Prevalence and some properties of verotoxin (Shiga-like toxin)-producing Escherichia coli in seven different species of healthy domestic animals

Shiga toxin-producing and attaching and effacing Escherichia coli in cats and dogs in a high hemolytic uremic syndrome incidence region in Argentina

Examination for heat-labile, heatstable, and Shiga-like toxins and for the eaeA gene in Escherichia coli isolates obtained from dogs dying with diarrhea: 122 cases (1992-1996)

Characteristics of alphahemolytic strains of Escherichia coli isolated from dogs with gastroenteritis

Cytotoxin activity on Vero cells among Escherichia coli strains associated with diarrhea in cats

Detection of Esche richia coli Shiga toxin (stx) and enterotoxin (estA and elt) genes in fecal samples from non-diarrheic and diarrheic greyhounds

Lepirudin prevents lethal effects of Shiga toxin in a canine model

Haemolytic-uraemic syndrome caused by a non-O157 : H7 Escherichia coli strain in experimentally inoculated dogs

Hemolytic-uremic syndrome in a dog

Haemolytic-uraemic syndrome in a dog

Hemolytic uremic syndrome in dogs

Pythiosis of the digestive tract in dogs from Oklahoma

Esophagitis due to Pythium insidiosum infection in two dogs

Prostatic pythiosis in a dog

Grooters AM: Pythiosis, lagenidiosis, and zygomycosis in small animals

Development of a nested polymerase chain reaction assay for the detection and identification of Pythium insid iosum

PCR-based detection of Pythium and Lagenidium DNA in frozen and ethanol-fixed animal tissues

Development and evaluation of an enzyme-linked immunosorbent assay for the serodiagnosis of pythiosis in dogs

Urinary tract manifestations of protothecosis in dogs

Infectious Diseases of the Dog and Cat

Ileocolitis associated with Anaerobiospirillum in cats

Identification of three clusters of canine intestinal spirochaetes by biochemical and 16S rDNA sequence analysis

Canine intestinal spirochetes consist of Serpulina pilosicoli and a newly identified group provisionally designated "Serpulina canis" sp. nov

Colonisation of pet shop puppies with Brachyspira pilosicoli

Light microscopic and ultrastructural changes in the ceca of chicks inoculated with human and canine Serpulina pilosicoli

Studies on a canine intestinal spirochete: scanning electron microscopy of canine colonic mucosa

Classification of Brachyspira spp. isolated from Swedish dogs

Brachyspira pilosicoli isolated from two Beagles and one mongrel in Japan

Efficacies of erythromycin and chloramphenicol in extinguishing fecal shedding of Campylobacter jejuni in dogs

Household pets as a potential reservoir for Clostridium difficile infection

Gastrointestinal carriage of Clostridium difficile in cats and dogs attending veterinary clinics

Fecal shedding of Clostridium difficile in dogs: a period prevalence survey in a veterinary medical teaching hospital

Clostridium difficile: a survey of fecal carriage in cats in a veterinary medical teaching hospital

Evaluation of five enzyme immunoassays compared with the cytotoxicity assay for diagnosis of Clostridium difficile-associated diarrhea in dogs

Prominent animal mycoses from various regions of the world

Grooters AM: Pythiosis, lagenidiosis, and zygomycosis in small animals

Pythiosis of the digestive tract in dogs from Oklahoma

Ultrasonographic features of canine gastrointestinal pythiosis

Serodiagnosis of human and animal pythiosis using an enzyme-linked immunosorbent assay

Development of a nested polymerase chain reaction assay for the detection and identification of Pythium insid iosum

Development and evaluation of an enzyme-linked immunosorbent assay for the serodiagnosis of pythiosis in dogs

Morphologic features and development of granulomatous vasculitis in feline infectious peritonitis

Neutrophil survival factors produced by macrophages in cats infected with feline infectious peritonitis virus contribute to the pathogenesis of granulomatous lesions

An uncommon intestinal manifestation of feline infectious peritonitis: 26 cases

Rectal strictures in 19 dogs

Transrectal stapling for colonic resection and anastomosis

Constipation, obstipation, and megacolon

Pathogenesis, diagnosis, and therapy of feline idiopathic megacolon

Congenital large intestinal hypoganglionosis in a domestic shorthair kitten

Lumbosacral intervertebral disk disease in six cats

Pathophysiology of gastrointestinal disease

Alterations in colonic smooth muscle function in cats with idiopathic megacolon

Cisapride stimulates contraction of feline idiopathic megacolonic smooth muscle

Segmental colonic dysfunction in cats with idiopathic megacolon

Pelvic osteotomy as a treatment for constipation in cats with acquired stenosis of the pelvic canal

Clinical, biochemical, acidbase, and electrolyte abnormalities in cats after hypertonic sodium phosphate enema administration

Attaching and effacing and enterotoxigenic Escherichia coli associated with enteric colibacillosis in the dog

Attaching and effacing bacteria in the intestines of calves and cats with diarrhea

Attaching-effacing bacteria in animals

Prevalence of Salmonella in raw meat used in diets of racing greyhounds

Preliminary assessment of the risk of Salmonella infection in dogs fed raw chicken diets

Isolation of Salmonella species from imported dog chews

Infectious Diseases of the Dog and Cat

Detection of Salmonella spp in fecal specimens by use of real-time polymerase chain reaction assay

Yersinia enterocolitica in two dogs

Isolation of Yersinia enterocolitica from a dog with chronic enteritis: a case report

Yersinia pseudotubercu losis in a Persian cat

The classification of feline colitis

An uncommon intestinal manifestation of feline infectious peritonitis: 26 cases (1986-1993)

Cecal inversion in eight dogs

Intussusception in dogs and cats

Intussusception in the dog and cat: a review of 45 cases

Intussusception in dogs and cats

Intussusception in 12 cats

Ultrasonographic signs of intestinal intussusception associated with acute enteritis or gastroenteritis in 19 young dogs

Enteroplication for the prevention of intussusception recurrence in dogs: 31 cases

Complications of enteroplication for the prevention of intussusception recurrence in dogs

Enteroplication in cats, using suture of N-butyl cyanoacrylate adhesive

Disseminated histoplasmosis in cats

Disseminated histoplasmosis in dogs

Update on canine and feline fungal diseases

Itraconazole for the treatment of histoplasmosis in cats

Use of corticosteroids for treating dogs with airway obstruction secondary to hilar isolated rectum circular smooth muscle

R093877 enhances defecation frequency in conscious cats

Mosapride-use in gastrointestinal disorders

Comparison of effect of Mosapride citrate and existing 5-HT 4 receptor agonists on gastrointestinal motility, in vivo and in vitro

Ultrasonographic evaluation of vincristine-induced gastric hypomotility and the prokinetic effect of Mosapride citrate in dogs

Changes in colonic motility induced sennosides in dogs: evidence of a prostaglandin mediation

Prostanoids stimulate duodenal and colonic smooth muscle contraction

Nizatidine and ranitidine, but not cimetidine, stimulate feline colonic smooth muscle contraction

Subtotal colectomy for treatment of chronic constipation associated with idiopathic megacolon in cats: 38 cases (1979-1985)

Enteric function in cats after subtotal colectomy for treatment of megacolon

Subtotal colectomy for treatment of obstipation secondary to pelvic fracture malunion in cats

Symphyseal distraction-osteotomy using a novel spacer of spirally fashioned orthopaedic wire for the management of obstipation

Comparison of biofragmentable anastomosis ring and sutured anastomoses for sub-total colectomy in cats with idiopathic megacolon

Large intestine

Preservation versus excision of the ileocolic junction during colectomy for megacolon: a study of 22 cats

Irritable bowel syndrome-current approach to symptoms, evaluation, and treatment

Overview of neurogastroenterologygastrointestinal motility and function GI disorders

Treatment of a chronic idiopathic large-bowel diarrhea in dogs with a highly digestible diet and soluble fiber: a retrospective review of 37 cases

Nonlymphoid intestinal neoplasia in 32 dogs and 14 cats

Gastrointestinal lymphoma in 20 dogs

Leiomyosarcomas in dogs

Butyrate and propionate stimulate feline longitudinal colonic smooth muscle contraction

Acute mouse and chronic dog toxicity studies of danthron, dioctyl sodium sulfosuccinate, poloxalkol and combinations

Carbohydrate digestion by the domestic cat

Nitric oxide as a mediator of bisacodyl and phenolphthalein laxative action: induction of nitric oxide synthase

Pharmacological management of constipation

Pharmacologic management of chronic constipation

Lubiprostone: chloride channel activator for chronic constipation

Linaclotide-a secretagogue and antihyperalgesic agent

Effect of laxatives and pharmacologic therapies in chronic idiopathic constipation: systematic review and metaanalysis

Two randomized trials of linaclotide for chronic constipation

Gastrointestinal motility disorders and gastrointestinal prokinetic therapy

Clinical pharmacology of cisapride

5-HT-induced colonic contractions: enteric locus of action and receptor subtypes

Effects of cisapride on feline colonic smooth muscle function

Gastrointestinal prokinetic therapy: serotonergic drugs

Pharmacokinetics and suggested oral dosing regimen of cisapride: a study in healthy cats

Comparison of tegaserod and its main metabolite with cisapride and erythromycin on cardiac repolarization in the isolated rabbit heart

The canine Purkinje fiber: an in vitro model system for acquired long QT syndrome and drug-induced arrhythmogenesis

Cisapride for intestinal constipation (review)

SDZ HTF 919 stimulates canine colonic motility and transit in vivo

Serotonin type-4 receptors modulate the sensitivity of intramural mechanoreceptive afferents of the cat rectum

Tegaserod normalizes opioidinduced bowel dysfunction in dogs

Dose-dependent effects after oral and intravenous administration of R093877 on colonic motility in conscious dogs

Pharmacological characterization of 5-HT receptors mediating relaxation of canine 31. Sorenmo K: Feline epitheliotropic intestinal malignant lymphoma: 10 cases

Colorectal adenocarcinoma in dogs

Ultrasonographic and clinicopathologic findings in 21 dogs with intestinal adenocarcinoma

Dysregulation of β-catenin is common in canine sporadic colorectal tumors

Cyclo-oxygenase-2 expression in spontaneous intestinal neoplasia of domestic dogs

Dietary polyunsaturated fatty acids and colorectal neoplasia

Late complications of pelvis irradiation in 16 dogs

Large intestine

Slatter DH editor: Textbook of Small Animal Surgery

Antimicrobial prophylaxis in colorectal surgery: a systematic review of randomized controlled trials

Colorectal blood supply in dogs

GD: Rectal resection in the dog. A new surgical approach and evaluation of its effect on fecal continence

A retrospective evaluation of the rectal pull-through technique. Procedure and post-operative complications

Bilateral pubic and ischial osteotomy for surgical management of caudal colonic and rectal masses in six dogs and a cat

Transrectal stapling for colonic resection and anastomosis (10 cases)

Short chain fatty acids and postoperative intestinal adaptation

Maintenance of GI function after bowel surgery and immediate full enteral nutrition. I. Doubling of canine colorectal anastomotic bursting pressure and intestinal wound mature collagen content

Feline gastrointestinal lymphoma: 67 cases

Chemotherapy with cyclophosphamide, vincristine, and prednisolone

A comparison of doxorubicin and COP for maintenance of remission in cats with lymphoma

Chemotherapy of lymphoma in 75 cats

Treatment and prognostic factors in lymphoma in cats: 103 cases

Single agent chemotherapy with doxorubicin for feline lymphoma: a retrospective study of 19 cases

Rescue therapy with doxorubicin-based chemotherapy for relapsing or refractory feline

Intestinal leiomyosarcomas in six dogs

Cecal smooth muscle neoplasia in the dog

Colorectal leiomyomas in seven dogs

Gastrointestinal stromal tumors and leiomyomas in the dog: a histopathologic, immunohistochemical, and molecular genetic study of 50 cases

Overexpression of p53 tumor suppressor protein in spontaneously arising neoplasms in dogs

Immunohistochemical detection of P-glycoprotein in formalin-fixed and paraffin-embedded normal and neoplastic canine tissues

Immunohistochemical staining characteristics of canine gastrointestinal stromal tumors

Aberrations of the p53 tumor suppressor gene in various tumors in dogs

Immunohistochemical detection of p53 tumor suppressor gene protein in canine epithelial colorectal tumors

Mucocutaneous plasmacytomas in the dog

Metastatic extramedullary plasmacytoma of the colon and rectum in a dog

Malignant colonic neoplasia in cats

Feline intestinal adenocarcinoma

Alimentary lymphoma in cats

Alimentary lymphoma in cats and dogs

Feline intestinal T-cell lymphoma: assessment of morphologic and kinetic features in 30 cases

Immunophenotypic and histologic classification of 50 cases of feline gastrointestinal lymphoma

Chronic inflammatory and non-inflammatory diseases of the gastrointestinal tract in cats: diagnostic advantages of full thickness intestinal and extra-intestinal biopsy

Treatment of feline gastrointestinal small-cell lymphoma with chlorambucil and glucocorticoids

Low grade alimentary lymphoma: clinicopathological findings and response to treatment in 17 cases

Outcome of cats with low-grade lymphocytic lymphoma: 41 cases

Gastric Helicobacter species as a cause of feline gastric lymphoma

Environmental tobacco smoke and risk of malignant lymphoma in pets

Canine intestinal adenocarcinoma and carcinoid

Hypoglycemia in four dogs with smooth muscle tumors

lymphoma: a retrospective study of 23 cases

Response rates and survival times for cats with lymphoma treated with UWM chemotherapy protocol: 38 cases

Results of chemotherapy for cats with alimentary malignant lymphoma: 21 cases

Combination chemotherapy in feline lymphoma: treatment outcome, tolerability, and duration in 23 cats

Colonic perforation after corticosteroid and surgical treatment of intervertebral disc disease in a dog

Colonic perforation following neurosurgical procedures and corticosteroid therapy in four dogs

Colonic perforation in corticosteroid-treated dogs

Sigmoid diverticular perforation in neurosurgical patients receiving high dose corticosteroids

Perforation of the gastrointestinal tract in patients receiving steroids for neurologic disease

Steroids, non-steroidal anti-inflammatory drugs, and sigmoid diverticular abscess perforation in rheumatic conditions

Effect of cortisone on mucoprotein secretion by the gastric antrum of dogs: Pathogenesis of steroid ulcer

Glucocorticoids inhibit the expression of an inducible, but not the constitutive, nitric oxide synthase in vascular endothelial cells

Concurrent use of indomethacin and dexamethasone increases the risk of spontaneous intestinal perforation in very low birth weight neonates

Gastrointestinal tract perforation in dogs treated with a selective cyclooxygenase-2 inhibitor: 29 cases

Comparison of peritoneal fluid and peripheral blood pH, bicarbonate, glucose, and lactate concentration as a diagnostic tool for septic peritonitis in dogs and cats

A granulomatous colitis of dogs with histologic resemblance to Whipple's disease

The comparative importance of E. coli antigen in granulomatous colitis of Boxer dogs

Adherent and invasive Escherichia coli is associated with granulomatous colitis in Boxer dogs

Intestine