Gastrointestinal Disease Flashcards

Question

Vascular ring anomalies are congenital malformations of the major arteries of the heart that entrap the intrathoracic esophagus and cause esophageal obstruction. Persistent right aortic arch (PRAA) is the best-documented anomaly in both dogs and cats; it occurs when the embryonic .........aortic arch (rather than the ............... aortic arch) becomes the functional adult ........... Circular entrapment of the esophagus occurs by the aorta on the .........., the ligamentum arteriosum dorsolaterally on the left, the pulmonary trunk on the ........., and the heart base ventrally.

Answer 1

Vascular ring anomalies are congenital malformations of the major arteries of the heart that entrap the intrathoracic esophagus and cause esophageal obstruction. Persistent right aortic arch (PRAA) is the best-documented anomaly in both dogs and cats; it occurs when the embryonic right aortic arch (rather than the left fourth aortic arch) becomes the functional adult aorta. Circular entrapment of the esophagus occurs by the aorta on the right, the ligamentum arteriosum dorsolaterally on the left, the pulmonary trunk on the left, and the heart base ventrally. This anomaly is considered to have a familial tendency, because German Shepherds and Irish Setters appear to be predisposed. Other less common vascular anomalies include persistent right or left subclavian arteries, double aortic arch, persistent right dorsal aorta, left aortic arch and right ligamentum arteriosum, and aberrant intercostal arteries. Focal leftward deviation of the trachea near the cranial border of the heart in DV or VD radiographs is a reliable sign of PRAA in young dogs. Definitive therapy for PRAA is surgical ligation and transection of the ligamentum arteriosum.

Answer 2

Congenital diverticula are due to developmental abnormalities of the esophagus that permit herniation of the mucosa through the muscularis. Acquired diverticula are classified as either pulsion or traction forms. Pulsion diverticula result from conditions of increased intraluminal pressure secondary to obstruction (stricture or foreign body) or altered motility. Traction diverticula result from periesophageal inflammation and fibrosis. With the traction form, contraction of fibrotic adhesions leads to eversion and outpouching of the esophageal wall. The accumulation of ingesta (impaction) within diverticula leads to esophagitis, mechanical obstruction (seen with large diverticula), and disturbed esophageal motility.

Answer 3

Both congenital and acquired fistulas have been described. Acquired fistulas are usually associated with retained esophageal foreign bodies, especially bones. Other causes include trauma, neoplasia, or periesophageal inflammation. Clinical signs are primarily associated with the respiratory tract and include coughing and dyspnea. Survey thoracic radiographs usually reveal a localized alveolar, bronchial, or interstitial lung pattern or a combination of these patterns

Answer 4

Esophageal fibrosarcoma and osteosarcoma are the most common malignant tumors in dogs. Squamous cell carcinoma is the most commonly diagnosed primary esophageal tumor in cats. Periesophageal tumors arising from a variety of adjacent structures—lymph nodes, thyroid, thymus, and heart base—cause local esophageal invasion, direct mechanical obstruction, or both.

Answer 5

(1) sliding hiatal hernia, which is a cranial displacement of the distal esophagus and stomach into the mediastinum through the esophageal hiatus; and (2) periesophageal hiatal hernia, which involves cranial displacement of a portion of the stomach into the mediastinum through a defect adjacent to the esophageal hiatus. Most hiatal hernias are probably congenital and occur as developmental defects (enlargement) of the esophageal hiatus or phrenicoesophageal ligament. Acquired hiatal hernias occasionally occur secondary to trauma (via damage to diaphragmatic nerves and muscles resulting in hiatal laxity) and respiratory distress (caused by increased negative intrathoracic pressure seen with intermittent airway obstruction [laryngeal paralysis]). Regardless of the cause, hiatal herniation reduces LES pressure and leads to gastroesophageal reflux, esophagitis, and segmental or diffuse esophageal hypo motility. Gastrointestinal intussusception is a rare disorder of young dogs caused by invagination of the stomach and occasionally other structures—such as the spleen, proximal duodenum, and pancreas—into the esophagus

Answer 6

The paucity of bacteria in the stomach and proximal small intestine is due to acid, bile, and pancreatic secretions that kill most ingested bacteria and because of propulsive motor activity in the distal small intestine, which impedes stable bacterial colonization. However, bacterial density dramatically increases in the distal small bowel and in the large intestine increases to 1011 to 1012 bacteria per gram of luminal contents. A large proportion of the fecal mass consists of bacteria—about 60% of fecal solids

Answer 7

-metabolic activities that cultivate energy and nutrients -important trophic effects on intestinal epithelia and immune structure and function -protection of the colonized host against invasion by pathogenic microbes Gut flora might also be an essential factor in specific pathologic disorders, including inflammatory bowel disease, small intestinal bacterial overgrowth, and infectious causes for gastroenteritis.

Answer 8

Quantitative analysis of fecal flora has shown that anaerobic bacteria outnumber aerobic bacteria by a factor of 100 to 1000. The most commonly isolated anaerobic bacteria comprised the genera Bacteroides, Clostridia, Eubacteria, and Fusobacteria, while Pasteurella spp. were the predominant aerobic species It is now realized that the composition of gut flora in healthy dogs and cats is distinctly different. Healthy cats were shown to have a large number of total and anaerobic bacteria in the small intestines

Answer 9

A major metabolic function of the colonic microflora is the fermentation of nondigestible dietary residues into short-chain fatty acids (SCFA), including acetate, propionate, and butyrate. Butyrate is almost completely consumed by the colonic epithelium, where it serves as a major source of energy for colonocytes. The outcomes of this complex metabolic activity are recovery from metabolic injury, absorbable substrates for the host, and a supply of energy and nutrition for bacterial growth and proliferation.

Answer 10

These resident bacteria can break down dietary carcinogens; synthesize biotin, folate, and vitamin K; metabolize bile salts; and assist in the absorption of calcium, magnesium, and iron. Colonization increases glucose uptake in the gut, whereas germ-free mice require a greater caloric intake to maintain a normal body weight. It has been proposed that an individual's gut microbiota has a specific metabolic efficiency, and differences in microbial composition might regulate energy storage and predispose obesity in adults

Answer 11

Along the epithelium, resident enteric bacteria form a natural barrier against colonization by exogenous microbes.

Answer 12

Surface enterocytes, M cells, and dendritic cells (DCs). Surface enterocytes are interconnected by tight junctions and are covered in mucus that promotes antigenic exclusion. They sense danger signals within the luminal microenvironment and respond by secreting defensins, immunoglobulin A, chemokines, and cytokines, which initiate and direct innate and adaptive immune responses. M cells, which are specialized epithelial cells that overlie lymphoid follicles, sample luminal antigens and deliver their products to DCs and other antigen-presenting cells. DCs provide further immune surveillance via direct sampling of gut contents by either entering or extending dendrites between surface enterocytes.Furthermore, DCs can ingest and retain live commensal bacterial and transport them to mesenteric lymph nodes where immune responses to these bacteria might be produced locally. Accordingly, access of commensal bacteria to the internal environment is prevented.

Answer 13

The family of toll-like receptors (TLRs) and the nucleotide-binding oligomerization domain (NOD1 and NOD2) molecules.

Answer 14

The TLRs comprise a class of transmembrane PRRs that play a key role in microbial recognition, induction of antimicrobial genes, and the control of adaptive immune responses.

Answer 15

The NODs are a structurally distinct family of intracellular PRRs that exert antimicrobial activity and prevent pathogenic invasion.

Answer 16

(1) recognition of molecular patterns present on pathogens (2) expression at the interface with the “environment” of the gastrointestinal tract (3) induction of secretion of proinflammatory and antiinflammatory cytokines and chemokines that link to adaptive immunity; and (4) induction of antimicrobial effector pathways.

Answer 17

Thus, TLRs expressed by both nonepithelial cell types (e.g., macrophages, DCs) and by intestinal epithelial cells (e.g., TLR4 by Lipopolysaccharide/LPS and TLR5 by bacterial flagellin) play key functional roles in epithelial cell signaling of innate immune defense

Answer 18

Toll-like receptor (TLR) ligand diversity: Different pathogen-associated molecular patterns present on commensal and pathogenic bacteria selectively activate TLRs and link to the adaptive immune system. The physiologic benefits of these bacterial-mucosal interactions promote mucosal tolerance and the maintenance of commensal homeostasis.

Answer 19

Different TLRs selectively recognize different PRRs (i.e., each TLR binds specific “molecular signatures” of different classes of microorganisms), and each initiates signaling through conserved pathways, such as nuclear factor kappa B and mitogen-activated protein kinases signal transduction pathways. These downstream effects involve transcriptional activation of genes encoding proinflammatory and antiinflammatory cytokines and chemokines as well as induction of costimulatory molecules.

Answer 20

Promotes host-defense and tissue-repair responses, thereby maintaining mucosal and commensal homeostasis. This programmed response creates a chemotactic gradient for the entry of neutrophils, monocytes, and T lymphocytes into the mucosa, which facilitates the clearance of invading pathogens.

Answer 21

........such as NOD2/CARD15 mutation in Crohn's disease, or environmental triggers, such as pathogenic infection or use of nonsteroidal antiinflammatory drugs. Therefore, bacterial dysrecognition and mucosal intolerance through aberrant TLR/NOD signaling stimulates exaggerated proinflammatory responses that lead to chronic inflammation via cytokine and chemokine production in genetically susceptible hosts.

Answer 22

Animal models also suggest that the gut microbiota is a causative factor of IBD. Both clinical and research data indicate that resident microbiota likely play a pivotal role in driving the inflammatory process of companion-animal IBD. In separate studies, increased lamina propria myeloid/histiocyte antigen-positive macrophages, upregulated epithelial major histocompatibility complex class II molecule expression. In separate studies, dogs with IBD showed distinctly different duodenal microbial communities compared with healthy dogs, and bacteria-responsive TLR2, 4, and 9 were upregulated in the inflamed duodenal and colonic mucosa of diseased dogs.[39] This might lead to increased inflammation through interaction with the microbiota.

Answer 23

adherent/invasive Escherichia coli (AIEC),

Answer 24

Increased numbers of total or obligate anaerobic bacteria in duodenal juice, but controversy exists as to what bacterial quantity constitutes normal.

Answer 25

Antibiotic-responsive diarrhea (ARD)

Answer 26

(1) competition for nutrients—the bacterial binding of cobalamin, which impairs its intestinal absorption (2) bacterial metabolism of nutrients into secretory products (e.g., hydroxylated fatty acids, deconjugated bile salts) that promote colonic secretions (3) biochemical injury to the intestinal brush border, which decreases enzyme activity

Answer 27

ARD may develop secondary to disrupted barrier function, aberrant mucosal immunity, or qualitative changes in the enteric bacterial flora. Studies show that dogs with ARD may have selective IgA deficiency (German Shepherd breed) and increased mucosal CD4+ T cells and IgA plasma cells, which might reflect an underlying immunologic pathogenesis. The microbiota present in ARD generally consists of a mixed population of commensal aerobes and anaerobes that normally inhabit the intestines.

Answer 28

Remission of clinical signs following an antibiotic trial.

Answer 29

Clostridium perfringens, Clostridium difficile, Campylobacter spp., pathogenic E. coli, and Salmonella spp. Diarrhea attributable to perturbation in the intestinal microbiota may result from microbe proliferation, enterotoxin production, and/or mucosal invasion. Information regarding the pathogenesis of C. perfringens–associated diarrhea is limited but likely involves enterotoxigenic commensal isolates. Infection with Campylobacter jejuni is enhanced in crowded, unsanitary environments, where its production of cytotoxin and heat-labile toxin promote mucosal inflammation and fluid secretion, respectively.

Answer 30

Probiotics are iving microorganisms that, upon ingestion in sufficient numbers, impart health benefits beyond those of inherent basic nutrition. Probiotic bacteria have measurable host benefits that include the ability to improve epithelial barrier function, modulate the mucosal immune system, and alter the intestinal flora (Lactobacilli and bifidobacteria have been the most commonly used human probiotic).

Answer 31

Prebiotics are nondigestible dietary carbohydrates—lactosucrose, fructooligosaccharides (FOS), psyllium, bran—that stimulate the growth and metabolism of endogenous enteric protective bacteria upon consumption. Beneficial effects of prebiotics are also associated with the production of SCFA due to fermentation by colonic bacteria. Synbiotics are combinations of probiotics and prebiotics that are an emerging therapeutic modality.

Answer 32

The cardia, fundus, body, and antrum. The fundus and body expand to accommodate ingesta. The antrum is thick and muscular and grinds food into small particles that are triturated into the duodenum. The lower esophageal sphincter prevents reflux of ingesta into the esophagus, and the pyloric sphincter controls efflux into the duodenum Figure 269-1 Gastric anatomy of the empty and full stomach. 

Answer 33

The mucosa, muscularis, and serosa.

Answer 34

The mucosa has a superficial epithelium, gastric glands, and an innermost layer of smooth muscle, with fine structure and function varying depending on the gastric region. The mucosa in the cardia and pylorus is thinner and less glandular than in the fundus and body.

Answer 35

Mucous neck cells (pepsinogen A, gastric lipase) Parietal cells (acid, pepsinogen A, intrinsic factor) Chief cells (pepsinogen A) (Figure 269-2).

Answer 36

Enterochromaffin-like and somatostatin-producing cells in the fundus & Gastrin and somatostatin-producing cells in the antrum. (Localized small aggregates of lymphoid tissues are observed at the base of the gastric glands. Intertwined among gastric glands is a rich network of blood vessels, lymphatics, and nerves).

Answer 37

Beneath the submucosa are two layers of smooth muscle that run perpendicuar to each other. The serosa is the outermost layer.

Answer 38

Figure 269-2 Histologic appearance of the fundic mucosa.  Se denne!

Answer 39

Luminal peptides Digested protein Acetylcholine Gastrin-releasing peptide Histamine release from mast cells and binding of acetylcholine and gastrin to parietal cells also contribute to secretion. (Figure 269-3).

Answer 40

Figure 269-3 Regulation of acid secretion. ACh, Acetylchline receptor; ECL, enterochromaffin-like cell; GRP, gastrin-releasing peptide; H2, histamine H2 receptor; PGE, prostaglandin E2 receptor; (

Answer 41

Somatostatin released in response to gastric pH levels below 3

Answer 42

Unstimulated acid secretion in dogs and cats is minimal (in dogs,

Answer 43

In the stimulated state, H+/K+-ATPase and KCl transporters are incorporated into the parietal cell canalicular membrane; hydrogen ions, derived from the ionization of water within the perietal cells, are transported into the gastric lumen in exchange for K by H+/K+-ATPase. Potassium and chloride transporters in the canalicular membrane enable luminal transfer of potassium and chloride. OH− combines with CO2, catalyzed by carbonic anhydrase, to form HCO3−, which diffuses into the blood (the “alkaline tide”). Stimulation results in a rapid increase in fluid and hydrogen ion secretion, with pH rapidly declining to around pH 1. The concentrations of K+ (10 to 20 mmol/L) and Cl− (approximately 120 to 160 mmol/L) in gastric juice are higher than in plasma

Answer 44

The stomach is protected from gastric acid by a functional unit known as hydrogen ions, derived from the ionization of water within the perietal cells, are transported into the gastric lumen in exchange for K by H+/K+-ATPase. Potassium and chloride transporters in the canalicular membrane enable luminal transfer of potassium and chloride. OH− combines with CO2, catalyzed by carbonic anhydrase, to form HCO3−, which diffuses into the blood (the “alkaline tide”). Stimulation results in a rapid increase in fluid and hydrogen ion secretion, with pH rapidly declining to around pH 1.

Answer 45

The stomach is protected from gastric acid by a functional unit known as the gastric mucosal barrier (GMB). The GMB comprises tightly opposed epithelial cells coated with a layer of bicarbonate-rich mucus and an abundant mucosal blood supply that delivers bicarbonate, oxygen, and nutrients. Local production of prostaglandins (PGE2) is important in modulating blood flow, bicarbonate secretion, and epithelial cell renewal. When damage occurs, epithelial cells rapidly migrate over superficial mucosal defects aided by the local production of growth factors such as EGF (epidermal growth factor).

Answer 46

The difference in pressure between the stomach and the duodenum and the resistance to flow across the pylorus.

Answer 47

Carbohydrates, amino acids, and especially fats retard gastric emptying. The release of cholecystokinin (CCK) in response to fatty acids and amino acids, such as tryptophan, is one factor that slows gastric emptying. Large, undigestible solids are expelled from the stomach in the fasted state by phase III of the migrating motility complex in response to the release of motilin.

Answer 48

Digestion and Assimilation of Nutrients The stomach has a limited role in the digestion of proteins, fats, and micronutrients. Pepsin, which digests proteins, is secreted as pepsinogen in response to acetylcholine and histamine in tandem with gastric acid. Dog gastric lipase, which digests fat, is secreted in response to pentagastrin, histamine, prostaglandin E2, and secretin and parallels the secretion of gastric mucus. Although pepsin is active only at acid pH, dog gastric lipase remains active in the small intestine and constitutes up to 30% of total lipase secreted over a 3-hour period.

Answer 49

Although gastric lipase and pepsin are not essential for the assimilation of dietary fat and protein, the entry of peptides and fatty acids into the small intestine likely helps to coordinate gastric emptying and pancreatic secretion.

Answer 50

Intrinsic factor, which is necessary for cobalamin (vitamin B12) absorption, is produced by parietal cells and cells at the base of antral glands in the dog but not the cat. The importance of gastric intrinsic factor secretion in dogs is questionable, as the pancreas is the major site of secretion in both dogs and cats. Gastric acidity may also have an effect on the availability of minerals such as iron and calcium.

Answer 51

Helicobacter spp. are adapted to life in an acid environment and produce urease that catalyzes the formation of ammonia from urea to buffer gastric acidity. Other bacterial species cultured from the canine stomach—such as Proteus, Streptococcus, and Lactobacillus—may transiently increase after a meal or after coprophagia. Acid secretion and gastric emptying likely regulate much of this transient flora, and bacteria may proliferate in the event of gastric acid hyposecretion due to glandular atrophy or pharmacologic inhibition. From a diagnostic standpoint, it is important to realize that bacteria such as Escherichia coli and Proteus spp. produce urease that can lead to a false positive test result for Helicobacter spp.

Answer 52

Active abdominal effort, presence of bile

Answer 53

Gastropathies that are part of a more generalized disease process, such as Basenji and Lundehund gastroenteropathy.

Answer 54

Na : K <27 : 1

Answer 55

hemorrhagic gastroenteritis

Answer 56

chronic gastric bleeding.

Answer 57

lead toxicity.

Answer 58

Vomiting of gastric and intestinal contents usually involves the loss of chloride, potassium, sodium, and bicarbonate-containing fluid, and dehydration is variably accompanied by hypochloremia, hypokalemia, and hyponatremia. Determination of acid-base status by measurement of total CO2 or venous blood gas analysis enables the presence of metabolic acidosis or alkalosis to be detected. Metabolic acidosis is generally more common than metabolic alkalosis in dogs with GI disease.

Answer 59

Where the gastric outflow tract or proximal duodenum is obstructed, the loss of chloride may exceed that of bicarbonate, and hypochloremia, hypokalemia, and metabolic alkalosis occur.[15-17] The metabolic alkalosis is enhanced by elevated HCO3− conservation due to volume, and potassium and chloride depletion.[18] The net effect is a preferential conservation of volume at the expense of the extracellular pH. The renal reabsorption of almost all filtered bicarbonate and the exchange of sodium for hydrogen in the distal tubule promote an acid urine pH despite an extracellular alkalemia (“paradoxical aciduria”).

Answer 60

Metabolic alkalosis in patients with GI signs is not invariably associated with outflow obstruction and has been encountered in dogs with parvovirus enteritis and acute pancreatitis. Diseases characterized by acid hypersecretion, such as gastrinoma, may also be associated with metabolic alkalosis and acuduria: In this situation, hypochloremia, hypokalemia, metabolic alkalosis, and dehydration are likely due to the hypersecretion of gastric acid and its loss in vomitus.

Answer 61

Venous blood gases and plasma osmolality are often determined in animals suspected of ethylene glycol ingestion, with the findings of metabolic acidosis and a high osmolal gap (calculated by subtracting calculated from measured osmolality) supportive of ingestion.

Answer 62

Elevated BUN in the absence of elevated creatinine may indicate gastric bleeding. Low albumin may be detected in Basenji or Lundehund dogs with protein-losing gastroenteropathy, dogs with pythiosis, and dogs or cats with gastric neoplasia. Elevated globulin concentrations have been observed in Basenji gastroenteropathy, Pythium infection, and gastric plasmacytoma. Elevations in creatinine, urea, calcium, potassium, glucose, liver enzymes, bilirubin, cholesterol, triglycerides, and globulin and decreases in sodium, calcium, urea, or albumin frequently herald non-GI causes of vomiting.

Answer 63

Thorough urinalysis is important; for example, white cell casts in the urine may be the only evidence that pyelonephritis is the cause of vomiting and should not be overlooked. Coagulation testing is indicated in patients with melena or hematemesis to detect underlying coagulopathies and in those with acute abdomen to detect disseminated intravascular coagulopathy (DIC). Infectious diseases associated with vomiting and diarrhea require fecal examination for diagnosis to detect Giardia, endoparasites, Salmonella spp., Campylobacter spp., and parvovirus (ELISA) or serologic testing (feline leukemia virus [FeLV], feline immunodeficiency virus). Additional clinicopathologic tests are required to detect hypoadrenocorticism (ACTH stimulation), liver dysfunction (preprandial and postprandial bile acids), hyperthyroidism in cats (T4), pancreatitis (amylase and lipase, pancreas-specific if possible), and intestinal disease (serum cobalamin and folate).

Answer 64

Esophagitis, GI ulceration, mucosal hypertrophy, or copious amounts of gastric fluid when acid hypersecretion is suspected. In its simplest form, fasting gastric pH and serum gastrin are measured to determine whether acid hypersecretion is likely. The broad range of fasting, unstimulated gastric pH in dogs and cats (pH 1 to 8) makes definitive statements regarding acid production difficult. However, the presence of a gastric pH of less than 3 in the face of a high serum gastrin rules out the possibility of achlorhydria or mast cell tumor and raises the possibility of gastrinoma. Dogs with mast cell tumors and hyperhistaminemia-induced acid hypersecretion have low serum gastrin concentrations, whereas dogs with achlorhydria likely have a high gastrin but a gastric pH greater than 3. Measurement of serum gastrin following the intravenous infusion of secretin or calcium is used to further investigate the possibility of exogenous gastrin production by pancreatic tumors, or gastrinomas (Zollinger-Ellison syndrome. Provocative testing of gastric acid secretion with pentagastrin or bombesin stimulation may be performed to detect achlorhydria in patients with atrophic gastritis, or elevated serum gastrin and gastric pH levels higher than 3, and in those with idiopathic small-intestinal bacterial overgrowth to determine if achlorhydria is a contributing factor.

Answer 65

Marked by vomiting of sudden onset presumed to be due to a gastric mucosal insult or inflammation. In most patients the cause is inferred from the history, such as dietary indiscretion; the diagnosis is rarely confirmed by biopsy, and treatment is symptomatic and supportive. Animals with acute gastritis associated with drug toxicity, foreign body ingestion, or metabolic disorders frequently present with hematemesis, melena, concurrent diarrhea, or other signs of systemic illness; these require a more thorough diagnostic approach to determine the cause, as discussed above, and to provide optimal care. This author has found little evidence in the literature to support the role of viral infections such as parvovirus, distemper, or infectious canine hepatitis in acute gastritis.

Answer 66

The history may reveal access to or ingestion of spoiled food, garbage, toxins, medications, or foreign bodies. Signs of toxicity may be evident, such as jaundice and pallor with zinc ingestion, salivation or defecation with organophosphates toxicity or mushroom ingestion, and salivation and oral ulceration with chemical ingestion.

Answer 67

GASTRIC EROSION AND ULCERATION Gastric erosions and ulcers are associated with a number of primary gastric and nongastric disorders (Table 269-2). Clinical signs range in duration and severity, from acute to chronic and from mild to life threatening. The pathomechanisms underlying gastric damage can be broadly attributed to impairment of the GMB (defined above) through direct injury, interference with gastroprotective prostaglandins (PGE2), mucous or bicarbonate, decreased blood flow, and hypersecretion of gastric acid.

Answer 68

Metabolic:Hypoadrenocorticism, uremia, liver disease, mastocytosis, DIC, hypergastrinemia Inflammatory: gastritis Neoplastic: Leiomyoma, adenocarcinoma, lymphosarcoma Drug-induced: Nonsteroidal and steroidal antiinflammatories Hypotension: Hypotension, Shock, sepsis Idiopathic: Stress, spinal surgery, exercise-induced (sled dogs)

Answer 69

NSAIDs cause direct mucosal damage and may interfere with prostaglandin synthesis. Flunixin meglumine, aspirin, and ibuprofen have all been associated with erosions in healthy dogs

Answer 70

carprofen, meloxicam, derccoxib, and potentially etodolac

Answer 71

The mechanisms by which they induce damage are not clear. Unlike NSAIDs, their effects are not ameliorated by PGE2 analogs

Answer 72

Hypersecretion of gastric acid in response to histamine release from mast cell tumors and gastrin from gastrinomas has also been clearly implicated as a cause of gastroduodenal ulceration and esophagitis in dogs and cats.

Answer 73

Renal failure, hepatic failure, hypoadrenocorticism, and hypotension are frequently proposed as risk factors for gastric erosion or ulceration, although few details have been published on the pathogenesis, frequency, or severity of gastric damage in these conditions.

Answer 74

When accompanied by thrombocytosis and decreased iron saturation or low serum ferritin, these findings are characteristic of chronic bleeding and iron deficiency. The presence of a metabolic alkalosis, hypochloremia, hypokalemia, and acid urine is consistent with upper GI obstruction (physical or functional) or a hypersecretory state.

Answer 75

NSAID-associated ulcers tend to be found in the antrum and are not usually associated with marked mucosal thickening or irregular edges This contrasts with ulcerated tumors that frequently have thickened edges and surrounding mucosa.

Answer 76

Patients with a history of vomiting who are mildly dehydrated are usually responsive to crystalloids (e.g., LRS or 0.9% NaCl). Patients with signs of shock require more aggressive support. The volume deficit can be replaced with crystalloids at an initial rate of 60 to 90 mL/kg/hr then tailored to maintain tissue perfusion and hydration. Colloid solutions can also be used to treat animals in shock to reduce the amount of crystalloid required. required (e.g., Hetastarch, Haemaccel at 10 to 20 mL/kg IV over 4 to 6 hours). Plasma, colloids, packed cells, or whole blood are occasionally required to treat severe hypoproteinemia or anemia, which can develop in vomiting animals with severe ulceration or HGE. Central venous pressure monitoring and evaluation of urine output are necessary in patients with severe GI disease, particularly those complicated by third-space losses of fluid into the gut or peritoneum. The effect of vomiting on acid-base balance is hard to predict, and therapeutic intervention to correct acid-base imbalances should be based on blood gas determination. Where severe metabolic acidosis is present (pH

Answer 77

Pharmacologic inhibition of acid secretion can be effected by blocking H2 (cimetidine, ranitidine, famotidine), gastrin (proglumide), and acetylcholine (atropine, pirenzipine) receptors and by inhibiting adenyl cyclase (PGE analogs) and H+/K+-ATPase (e.g., omeprazole). Long-acting somatostatin analogs, such as octreotide, directly decrease the secretion of gastrin and gastric acid.

Answer 78

(see Figure 269-5). Famotidine is an attractive choice, as it does not inhibit P450 enzymes and can be given once daily. The additional prokinetic activity of ranitidine or nizatidine (mediated by anticholinesterase activity) may make them good choices in the face of delayed gastric emptying associated with defective propulsion

Answer 79

In patients with severe or persistent gastric ulceration that is refractory to H2 antagonists, more complete inhibition of gastric acid secretion can be achieved with an H+/K+-ATPase inhibitor, such as omeprazole. Omeprazole is the initial drug of choice in patients with acid hypersecretion secondary to mast cell tumors and gastrinoma (Zollinger-Ellison syndrome). Omeprazole has been shown to have few long-term side effects in dogs, but it should be used with caution in patients with liver disease and must be reviewed for interactions with drugs such as cisapride.

Answer 80

The combination of omeprazole and the long-acting somatostatin analog octreotide effectively reduced vomiting in a dog with gastrinoma. Octreotide can also be employed to rapidly decrease gastric acid secretion in patients discovered to have large ulcers at endoscopy, and it has been used to control gastric bleeding in people.

Answer 81

The PGE2 analog misoprostol protects against NSAID-induced erosions in dogs at doses that do not inhibit acid secretion and may be given to dogs receiving chronic NSAIDs for arthritis. The main side effect of misoprostol is diarrhea, and it should not be given to pregnant animals. The mucosal protectant polyaluminum sucrose sulfate (sucralfate) binds to areas denuded of mucosal epithelium, regardless of the underlying cause, and is useful for treating gastric erosions, ulcers, and esophagitis. Sucralfate can be given to patients receiving injectable antacids, but it may compromise absorption of other oral medications and is probably best separated from these by 2 hours or so. Sucralfate is probably the drug of choice for treating GI ulceration in patients receiving high doses of corticosteroids, because it is not dependent on the premise that acid is causing or delaying healing.

Answer 82

Mast cell tumors are thought to cause vomiting via the central effects of histamine on the chemoreceptor trigger zone (CRTZ) and the peripheral effects of histamine on gastric acid secretion, with resultant hyperacidity and ulceration.

Answer 83

Treatment of mastocyosis with H1 and H2 histamine antagonists (e.g., diphenhydramine and famotidine) should reduce the central and peripheral effects of histamine. Corticosteroids are used to decrease tumor burden. Where acid hypersecretion is present or is suspected, it is likely best managed with proton-pump inhibitors (e.g., omeprazole 1 mg/kg BID). Somatostatin analogs may also be useful for controlling refractory gastric acid hypersecretion (octreotide)

Answer 84

Antiemetics commonly used in dogs include Metoclopramide, which antagonizes D2-dopaminergic and 5HT3-serotonergic receptors and has cholinergic effects on smooth muscle, Phenothiazine derivatives, such as chlorpromazine and prochlorperazine, which are antagonists of α1- and α2-adrenergic, H1- and H2-histaminergic, and D2-dopaminergic receptors in the vomiting center and CRTZ; Ondansetron, which antagonizes peripheral 5HT3 receptors Maropitant (not more than 5 days), which antagonizes neurokinin-1 receptors.

Answer 85

Comparison of these antiemetics indicates greater efficacy of maropitant and ondansetron for controlling peripheral vomiting induced by ipecac than metoclopramide or chlorpromazine and similar efficacy of maropitant, chlorpromazine, and metoclopramide for controlling centrally mediated vomiting induced by apomorphine. Maropitant should not be used in puppies younger than 16 weeks of age; in puppies younger than 11 weeks of age, histologic evidence of bone marrow hypoplasia was seen at higher frequency and greater severity in puppies treated with maropitant than in control puppies. Nonselective cholinergic receptor antagonists such as atropine, scopolamine, aminopentamide, and isopropamide are generally avoided, as they may cause ileus, delayed gastric emptying, and dry mouth

Answer 86

Prophylactic antibiotic cover (e.g., cephalosporins, ampicillin) may be warranted in animals with shock and major GI barrier dysfunction. Initial choices in these situations include ampicillin or a cephalosporin (effective against gram-positive and some gram-negative and anaerobic bacteria), which can be combined with an aminoglycoside (effective against gram-negative aerobes) when sepsis is present and hydration status is adequate. Enrofloxacin is a suitable alternative to an aminoglycoside in skeletally mature patients at risk of nephrotoxicity from an aminoglycoside.

Answer 87

With volvulus the stomach twists about its axis, moving dorsally and left of the fundus. Both GD and GDV cause caudal caval obstruction and impair venous return to the heart. This results in hypovolemic shock that can be exacerbated by devitalization of the gastric wall, splenic torsion or avulsion, congestion of the abdominal viscera, endotoxic shock, and DIC. Studies in dogs with GDV recovering from gastropexy suggest that abnormal electrical activity and gastric emptying may be related to the development of GD. The interrelationship of volvulus and gastric distension is unclear, although the length of the hepatogastric ligament may facilitate torsion.

Answer 88

Hematologic changes are often restricted to an increase in hematocrit. Metabolic acidosis and hypokalemia were the most common abnormalities in one study. Metabolic acidosis is likely due to tissue hypoperfusion, anaerobic metabolism, and the accumulation of lactic acid.[50] Metabolic alkalosis may also occur and may be related to the sequestration of gastric acid or vomiting. Respiratory acidosis and alkalosis have been variably observed and reflect hypoventilation or hyperventilation, respectively. The variable nature of acid-base and electrolyte abnormalities in dogs with GDV indicates that fluid therapy should be individualized on the basis of blood gas and electrolyte measurements. Monitoring and correction of acid-base abnormalities are important, because they may predispose to cardiac arrythmias and muscle weakness. Coagulation abnormalities are usually consistent with DIC (thrombocytopenia, increased D-dimer or FDPs, reduced ATIII, prolongation of the APTT).

Answer 89

Fluid therapy of GDV dogs has traditionally consisted of shock doses of LRS (60 to 90 mL/kg/h) given via large-bore catheters into the cephalic or jugular veins. Experimental studies that have compared crystalloids (60 mL/kg, followed by 0.9% NaCl 20 mL/kg/hr) with hypertonic saline (7% NaCl in 6% dextran, 5 mL/kg, followed by 0.9% NaCl 20 mL/kg/hr) in dogs with GDV-induced shock indicate that hypertonic saline maintains better myocardial performance, higher heart rate, and lower systemic vascular resistance than crystalloids. The resuscitative dose of hypertonic saline was delivered in 5 to 10 minutes versus an hour for crystalloids. Fluid therapy should be aggressively monitored by frequent measurement of blood pressure, heart rate, PCV, and total solids and urine output. Potassium and bicarbonate are best administered on the basis of blood gas and electrolyte measurements. Hypokalemia is common after fluid therapy, and 30 to 40 mEq KCl/L should be added to fluids after the initial shock dose.

Answer 90

Electrolyte, acid-base, and hemostatic abnormalities, as well as due to reperfusion injury. Arrhythmias should be treated if they are associated with weakness or syncope and if persistent ventricular tachycardia at rates greater than 150 beats per minute are demonstrated. Arrhythmias are managed by correcting underlying acid-base, electrolyte, and hemostatic disturbances and administering lidocaine either as a bolus (1 to 2 mg/kg IV) or continuously (up to 50 to 75 µg/kg/min) and procainamide (10 mg/kg IM q6h and then orally if effective) when arrhythmias are persistent. It is important that plasma concentration of K+ and Mg2+ are normalized to enable effective antiarrhythmic therapy

Answer 91

Mild to moderate superficial lymphoplasmacytic gastritis with concomitant lymphoid follicle hyperplasia. Eosinophilic, granulomatous, atrophic, and hyperplastic gastritis are less common. Despite the high prevalence of gastritis, an underlying cause is rarely identified. In the absence of systemic disease, ulcerogenic or irritant drugs, gastric foreign objects, parasites (Physalloptera and Ollulanus spp.), and in rare instances fungal infections (Pythium insidiosum, Histoplasma spp.), it is usually attributed to dietary allergy or intolerance, occult parasitism, a reaction to bacterial antigens, or unknown pathogens. Treatment is often empirical but can serve to define the cause of gastritis, such as diet responsive, antibiotic responsive, steroid responsive, or parasitic.

Answer 92

In health, this system avoids active inflammation by antigen exclusion and the induction of immune tolerance. The development of intestinal inflammation in mice lacking the cytokines interleukin (IL)-10, transforming growth factor-beta (TGF-β), or IL-2 indicates the central importance of cytokines in damping down mucosal inflammation. An hypothesis exist that spontaneous mucosal inflammation may be the result of a loss of tolerance to the indigenous GI microflora. The role of these mechanisms in outbred species, such as the dog and cat, remains to be determined, but clearly loss of tolerance to bacterial or dietary antigens should be considered.

Answer 93

The epithelial cell is also emerging as a “general” in the inflammatory response, with gram-negative or pathogenic bacteria inducing proinflammatory cytokine (e.g., IL-8, IL-1β) secretion from epithelial cells, whereas commensal or bacteria such as Streptococcus faecium or Lactobacillus spp. induce the production of the immunomodulatory cytokines TGF-β or IL-10

Answer 94

By the production of IL-10 from macrophages and potentially by the epithelial cells themselves. In this context, dogs with lymphoplasmacytic gastritis of undetermined etiology showed a correlation between the expression of the immunomodulatory cytokine IL-10 and proinflammatory cytokines (IFN-α, IL-1β, IL-8).[

Answer 95

There is a high prevalence of gastric Helicobacter spp. infection in dogs- In contrast to people, in whom H. pylori infection predominates, dogs and cats are colonized by a variety of large spiral organisms. Cats can also be colonized by H. pylori but infection has been limited to a closed colony of laboratory cats. The large Helicobacter species found in dogs and cats do not attach to the epithelium but colonize the superficial mucus and gastric glands, particularly of the fundus and cardia, and may also be observed intracellularly- The differences between people, dogs, and cats may be attributed to differences in the virulence of the infecting Helicobacter spp. or in the host response. Studies that address this issue indicate that H. pylori evokes a more severe proinflammatory cytokine and cellular response in dogs and cats than natural or experimental infection with large Helicobacter spp.[ The limited mucosal inflammatory response and absence of clinical signs in the vast majority of dogs and cats infected with non–H. pylori Helicobacter spp., despite significant antigenic stimulation evidenced by seroconversion and lymphoid follicle hyperplasia, suggests that large gastric Helicobacter spp. are more commensal than pathogenic. With this in mind, it is interesting to speculate that it is the loss of tolerance to gastric Helicobacter spp., rather than the innate pathogenicity of these bacteria, that explains the development of gastritis and clinical signs in some dogs and cats. However, much still remains to be learned about the role of Helicobacter spp. in canine and feline gastritis. The general lack of knowledge of the pathogenicity of gastric Helicobacter spp. has meant that veterinarians are faced with the dilemma of either treating or ignoring spiral bacteria observed in biopsies from patients with chronic vomiting and gastritis. The author recommends treating (such as metronidazole, amoxicillin,bismuth subsalicylate) only symptomatic patients that have biopsy-confirmed Helicobacter spp. infection and gastritis.

Answer 96

Eosinophilia may prompt the consideration of gastritis associated with dietary hypersensitivity, endoparasites, or mast cell tumors. Hyperglobulinemia and hypoalbuminemia may be present in Basenjis with gastropathy or enteropathy or in dogs with gastric pythiosis. Panhypoproteinemia is a feature of gastroenteropathy in Lundehunds, moderate to severe generalized inflammatory bowel disease, GI lymphoma, and GI histoplasmosis. More specific testing, such as an ACTH stimulation test or serology for Pythium insidiosum, is performed based on the results of these initial tests.

Answer 97

Ollulanus tricuspis (feline stomach) Physalloptera spp Given the difficult diagnosis of Ollulanus and Physalloptera spp., empirical therapy with an anthelmintic such as fenbendazole may be warranted in dogs and cats with unexplained gastritis.

Answer 98

The presence of transmural thickening of the gastric outflow tract and histology that indicates pyogranulomatous inflammation raise the possibility of infection with fungi such as Pythium insidious.

Answer 99

The diet is usually restricted in antigens to which the patient has been previously exposed, such as a lamb-based diet if the patient has previously been fed chicken and beef, or it contains hydrolyzed proteins (usually chicken or soy) that may be less allergenic than intact proteins. Many of these diets are also high in carbohydrates and restricted in fat, which facilitates gastric emptying, and they may contain other substances, such as menhaden fish oil or antioxidants that may alter inflammation. The test diet is fed exclusively for a period of about 2 weeks, and vomiting episodes are recorded. If vomiting is improved, a challenge with the original diet is required to confirm a diagnosis of food intolerance. The introduction of a specific dietary component, such as beef, to the test diet is required to confirm dietary sensitivity. Patients with moderate to severe lymphoplasmacytic gastritis are usually started on a combination of a test diet and prednisolone. If gastritis is unresponsive to diet, prednisolone, and antacids, additional immunosuppression may be indicated. azathioprine (Chlorambucil is a safer in cats) Prokinetic agents such as metoclopramide, cisapride, and erythromycin can be used as an adjunct where delayed gastric emptying is present.

Answer 100

Treatment for occult parasites, dietary trials, and immunosuppression can be carried out as described above. Focal eosinophilic granulomas can be associated with parasites or fungal infection that should be excluded prior to immunosuppression with corticosteroids.

Answer 101

Atrophic gastritis in dogs and cats is often associated with a marked cellular infiltrate In humans, gastric disease is often not discovered until the patient presents with pernicious anemia secondary to cobalamin deficiency caused by a lack of gastric intrinsic factor. In contrast to humans, dogs and cats with atrophic gastritis have not been reported to develop cobalamin deficiency. This is probably because the pancreas, rather than the stomach, is the main source of intrinsic factor in these species. Achlorhydria has been described in dogs and may enable the proliferation of bacteria in the stomach and upper small intestine, although this has not been proven. Atrophic gastritis has been infrequently described in dogs and cats but does share some similarities with people. Atrophic gastritis characterized by reduction in parietal cells and hyperplasia of neuroendocrine cells has been associated with gastric adenocarcinoma in Lundehunds. Some of the adenocarcinomas displayed enterochromaffin-like cell differentiation, suggesting that hypergastrinemia secondary to fundic atrophy may be important in carcinogenesis. However, with the exception of the Lundehund, clear evidence that gastritis progresses to atrophy and gastric cancer in dogs or cats and the role of Helicobacter spp. or antigastric antibodies in the development of atrophy in dogs and cats remain to be determined.

Answer 102

hepatic or renal disease, achlorhydria, or gastrin-producing tumors, which should be pursued appropriately. Basenji gastoenteropathy is variably associated with fasting hypergastrinemia and exaggerated secretin-stimulated gastrin, a

Answer 103

Disorders of gastric motility can disrupt the storage and mixing of food and its expulsion into the duodenum. Normal gastric motility is the result of the organized interaction of smooth muscle with neural and hormonal stimuli. Delayed gastric emptying is the most commonly recognized manifestation of gastric motility disorders. Rapid gastric emptying and motility disorders associated with retrograde transit of bile or ingesta are less well defined. Delayed gastric emptying is caused by outflow obstruction or defective propulsion and is usually suspected by the vomiting of food at least 8 and often 10 to 16 hours after a meal. Vomiting of food less than 8 to 10 hours after ingestion is the most common sign. Vomiting may be projectile with pyloric stenosis. Abdominal distension, weight loss, melena, abdominal discomfort, distension, bloating, and anorexia are more variably present.

Answer 104

-Development of vomiting at weaning raises the possibility of pyloric stenosis. -Access to foreign bodies, bones, and medications is of obvious relevance to outflow obstruction. -Brachycephalic, middle-aged, small-breed dogs such as Shih Tzus seem predisposed to the syndrome of hypertrophic pylorogastropathy: pyloric outflow obstruction caused by hypertrophy of the pyloric mucosa and/or muscular is. -Gastric neoplasia -Gastric pythiosis -Large-breed, deep-chested dogs are more prone to GDV that may have an underlying problem with gastric emptying

Answer 105

metabolic alkalosis

Answer 106

In nonobstructive situations, gastric emptying can be enhanced and duodenogastric reflux inhibited by prokinetic agents such as metoclopramide, cisapride, erythromycin, or ranitidine. The choice of prokinetic depends on whether a central antiemetic effect is required, as with metoclopramide, or a combined antacid prokinetic (ranitidine) is indicated, or if treatment with one agent has been ineffective or has caused adverse effects, such as behavioral changes with metoclopramide. In addition to its prokinetic activity in the stomach and upper GI tract, metoclopramide has central antiemetic properties and is frequently an initial choice in patients with underlying metabolic diseases associated with vomiting and delayed gastric emptying. However, metoclopramide may only facilitate the emptying of liquids and is less effective in promoting organized gastroduodenal and intestinal motility than cisapride. Cisapride has no central antiemetic effects but is generally more potent in promotion of the gastric emptying of solids than metoclopramide, but it does have more drug interactions, and its availability is limited. Erythromycin releases motilin, acts at motilin receptors, and mimics phase III of the interdigestive migrating myoelectric complex, promoting the emptying of solids. Nizatidine and ranitidine have prokinetic activity attributed to an organophosphate-like effect. Where true prokinetic activity is required, cisapride and erythromycin appear to be the most efficacious

Answer 107

adenocarcinom, leiomyosarcoma, lymphosarcoma, fibrosarcoma, rare anaplastic sarcoma, and gastric extramedullary plasmacytoma. Benign tumors of the stomach include leiomyomas and, less frequently, adenomatous polyps. Benign GI neoplasia in the cat occurs at a much lower frequency than in the dog, although up to 36% of all GI neoplasia is reported to be benign. Malignant adenocarcinoma is the most common gastric neoplasm in dogs and accounts for 47% to 72% of all canine gastric malignancies.[98-101] Gastric adenocarcinoma is extremely rare in cats. The most common GI neoplasm in both cats and dogs is lymphosarcoma, although it most often involves several segments of the intestinal tract.

Answer 108

The lesser curvature and pyloric region as annular or stenosing lesions, and metastasis is frequent with involvement of lymph nodes, lungs, and liver

Answer 109

Feline gastric lymphoma is not associated with FeLV infection and has been recently categorized as large cell or small cell, with small-cell lymphoma being more localized to the GI tract and carrying a much better prognosis than large-cell lymphoma

Answer 110

lymphocytic-plasmacytic inflammation

Answer 111

The production of insulin-like growth factors.

Answer 112

diarrhea—a significant increase in the frequency, fluidity, or volume of feces.

Answer 113

Nutrient digestion and absorption while simultaneously protecting the body from a multitude of environmental threats. Therefore the SI, as well as being the main digestive organ, is also the largest and most complex immunologic organ in the body. Indeed, considering its complexity, minor daily variations in stool quality must be considered normal and need not be investigated.

Answer 114

Major dietary constituents must be hydrolyzed into monomers to be transported across the MVM. This is largely achieved within the SI by bile salt emulsification and hydrolysis by pancreatic enzymes: the SI merely provides the optimum environment in terms of solute, temperature, pH, and mixing. Normally only terminal hydrolysis of food polymers is performed by MVM enzymes.

Answer 115

Enterocyte metabolism is geared toward the production of brush-border proteins and the transfer of nutrients and water from the lumen to the blood. The major energy source for enterocytes is glutamine, derived from food. This explains the decline in villus structure, epithelial integrity, immune function, absorptive function in starvation, and the importance of glutamine and enteral nutrition

Answer 116

By active or facilitated carrier-mediated transport or passive diffusion. Endocytosis of small, antigenic peptides is of no nutritional significance but is involved in the neonatal absorption of colostral antibodies, and is crucial to the mucosal immune response in later life.

Answer 117

(Figure 270-1, A) (Figure 270-1, B) Folic acid is absorbed in the proximal SI. Cobalamin (vitamin B12) bound to intrinsic factor is absorbed in the ileum in a process that excludes potentially harmful analogs. Cats and dogs have less capacity to store cobalamin than humans; cats also lack the binding protein transcobalamin I and rapidly lose cobalamin via enterohepatic recycling. Thus severe cobalamin malabsorption can deplete stores of the vitamin in cats within a month.

Answer 118

In normal intestine, folate is absorbed in the proximal small intestine (SI) by means of carrier-mediated diffusion. Dietary cobalamin is initially protected from digestion by R-proteins and is then absorbed in the ileum through receptor-mediated endocytosis, bound to intrinsic factor (IF).

Answer 119

In diseased intestine, proximal and distal mucosal damage causes folate and cobalamin malabsorption, respectively. Reduced serum folate and/or cobalamin are markers for proximal and/or distal SI damage. Classically, small-intestinal bacterial overgrowth (SIBO) in humans causes increased folate uptake because of bacterial folate synthesis and decreased cobalamin uptake due to bacterial incorporation. However, these changes are poorly sensitive and cannot be used to reliably diagnose SIBO in dogs and cats: They do not correlate with antibiotic reponsiveness

Answer 120

Slow wave, segmental, and peristaltic contractions of the SI are generated by the coordinated contraction of smooth muscle. Interstitial cells of Cajal are coordinating pacemaker cells. Motility in the fasted state in dogs is characterized by three phases: a quiescent phase, one of minor contractile activity, and then one of migrating myoelectric (motor) complexes (MMCs). The short MMC phase sweeps undigested food, secretions, desquamated cells, and bacteria down the SI.

Answer 121

This “intestinal housekeeper” wave is induced by motilin secretion and can be stimulated by erythromycin at low doses; at higher doses, overstimulation may cause emesis. The duration of motility in the fed state is determined by the nature of the diet, with fats and fiber prolonging it. Segmental contractions slow intestinal transit and ensure mixing and digestion of nutrients, until peristalsis propels ingesta onward.

Answer 122

The net amount of fluid and electrolytes in the GI tract reflects a balance between absorption and secretion, with net absorption in health. However the daily fluxes are massive (~2.7 litres per day in a 20-kg dog), and the consequences of net loss are not only diarrhea but also rapid dehydration. (The pathophysiology of diarrhea is detailed in Chapter 48).

Answer 123

The resident bacterial flora is a diverse mixture of aerobic, anaerobic, and facultatively anaerobic bacteria. There are more than 200 species present, but many are unculturable, and it is only by molecular fingerprinting techniques that the true flora can be characterized. It influences a wide variety of parameters, such as villus size, enterocyte turnover, brush-border enzyme turnover, intestinal motility, digestion, and assimilation of nutrients. A stable enteric flora is important for excluding pathogens and stimulating the development of the mucosal immune system. Given the intimate interrelationship of a healthy intestine with its flora, indiscriminate use of antibiotics in dogs and cats with diarrhea or gastroenteritis is ill advised. Although the consequences of inappropriate antibiotic therapy are often mild and self-limiting, long-term metronidazole use may predispose to carcinogenesis. Postantibiotic salmonellosis has been fatal in cats and, most importantly, inappropriate usage may encourage antibiotic resistance.

Answer 124

Bacterial numbers increase from the duodenum to the colon. Factors maintaining this aboral gradient are luminal patency, motility, substrate availability, bacteriostatic and bacteriocidal secretions—gastric acid, bile, and pancreatic secretions—and an intact ileocolic valve.

Answer 125

Higher normal numbers are accepted in cats, SIBO has never been described in the species. So rather than bacterial numbers, more likely it is the balance within the flora and its interaction with the mucosa that are crucial for health and disease.

Answer 126

Epithelial surface receptors. (Figure 270-2).

Answer 127

The epithelium uses pattern recognition receptors (PRRs) to recognize bacterial markers called pathogen-associated molecular patterns (PAMPs) expressed by both commensals and pathogens (Figure 270-2). Various toll-like receptors (TLRs) and nucleotide oligomerisation domainlike receptors (NODs) are the PRRs of enterocytes that recognize PAMPS

Answer 128

TLR2 recognizes lipopeptides found in gram-negative bacteria; TLR4 recognizes lipopolysaccharides (LPS) in gram-negative bacteria; TLR5 recognizes the bacterial flagella protein, flagellin; and NOD recognizes bacterial lipopolysaccharides

Answer 129

GASTROINTESTINAL IMMUNE SYSTEM The SI mucosa has a general barrier function (Web Box 270-1) and must generate a protective immune response against pathogens while remaining “tolerant” of harmless antigens, such as commensal bacteria and food. Despite advances in our understanding of the structure of and interactions with the immune system—and the role of bacterial recognition systems, such as TLRs—it is still unclear what prompts the SI to respond to or become tolerant of a particular antigen.

Answer 130

The mucosa-associated lymphoid tissue (MALT) occurs at internal body surfaces; in the intestine it is termed gut-associated lymphoid tissue (GALT) and comprises inductive and effector sites. Inductive sites comprise Peyer's patches (PPs), isolated lymphoid follicles, and the mesenteric lymph nodes (MLNs). Effector sites comprise the intestinal LP and epithelium Such a distinction is not absolute, however, and the functions of these different sites overlap. (Web Figure 270-2).

Answer 131

B lymphocytes are present in the follicular region of PPs and in the LP, mainly as plasma cells and mostly in the intestinal crypts, where they secrete IgA.

Answer 132

T lymphocytes are conventional alpha/beta T cell receptor types. An evolutionarily older (gamma/delta) T cell population also exists and is considered a primitive first-line defense. T lymphocytes can be further subdivided on the basis of expression of CD4 and CD8 molecules.

Answer 133

CD4+ T cells, classical “helper” T cells, recognize antigenic peptide presented by major histocompatibility complex class II (MHC II) molecules on antigen-presenting cells (APCs), whereas CD8+ T cells, usually cytotoxic cells, are MHC class I restricted.

Answer 134

In the canine LP, T cells are most numerous in the upper villus regions and are mostly the alpha/beta, CD4+ phenotype. However, in the feline LP, CD8+ T cells outnumber the CD4+ population. Most LP lymphocytes are highly differentiated, which implies that they receive continuous antigenic and mitogenic stimulation, probably from the endogenous microbial flora.

Answer 135

The T cells in the intestinal epithelium, the intraepithelial lymphocytes (IELs), are a heterogeneous population; most are CD8+ cells, which may be of either the alpha/beta or the gamma/delta phenotype, depending on the species. Known functions of IELs include cytolytic activity and cytokine production, which suggests that these cells play roles in epithelial surveillance and in the maintenance of mucosal immune homeostasis.

Answer 136

Dendritic Cells Dendritic cells (DCs) function predominantly as APCs and can be found in both inductive (PP) and effector (LP) tissues. In effector tissues their main function is antigen sampling, whereas in inductive sites they are responsible for generating acquired immune responses and tolerogenesis. Follicular DCs store antigen to provide continued stimulation to memory B cells

Answer 137

Other Immune Cells[204,207,226-232] Macrophages are present in the PP and LP. Their functions include phagocytosis, antigen presentation, and immunoregulation, and they secrete: cytokines chemokines inflammatory mediators; including tumor necrosis factor-alpha (TNF-α), eicosanoids, and leukotrienes. Neutrophils are present in small numbers, although their numbers increase with mucosal inflammation.

Answer 138

Histamine, heparin, eicosanoids, and cytokines. MCs express the high-affinity IgE receptor (FcϵRI), which can bind IgE, causing MC degranulation and release of these mediators.

Answer 139

In dogs, eosinophils are a prominent population in the LP, especially in the crypts. Eosinophils may have proinflammatory roles, especially in allergic processes, because they are a rich source of proinflammatory mediators, cytokines, and chemokines.

Answer 140

First, they exclude antigen. Second, they express surface TLRs that interact with the enteric flora. Third, they may present antigen through expression of MHC II. Fourth, enterocytes can produce inflammatory mediators, chemokines, and cytokines.

Answer 141

In dogs, MHC II is expressed by enterocytes but is largely absent from enterocytes of cats, although it is upregulated in inflammation.

Answer 142

Substance P, which can cause neurogenic inflammation via neurokinin (NK) receptors. Bidirectional communication may also exist, in which release of mediators by immune cells (e.g., MCs) can generate axon reflexes and thereby modulate intestinal motility, secretion, and absorption

Answer 143

A large array of cytokines is present in the SI, and these molecules can be grouped into proinflammatory, immunoregulatory, and chemokinetic types.

Answer 144

Different CD4+ T cell populations have different patterns of cytokine secretion and can differentially regulate distinct arms of the immune system (i.e., humoral and cell-mediated). In vitro, two principal populations of CD4+ T cells exist: a T-helper 1 (Th1) population that produces interleukin-2 (IL-2), interferon-gamma (IFN-γ), and TNF-β and a T-helper 2 (Th2) population that produces IL-4, IL-5, IL-6, and IL-10.

Answer 145

Other populations (Th3, Treg, Th17) with downregulatory functions also have been identified that predominantly secrete TGF-β, IL-10, or IL-17, respectively. Many other cell types also may produce cytokines (see above), and it is the local cytokine milieu that determines the predominant type of immune response.

Answer 146

Lymphocytes traffic between inductive and effector sites. Homing pathways are mediated by leukocyte-endothelial interactions through differential expression of homing receptors, or addressins. The most important interaction for mucosal lymphocytes occurs between alpha4/beta7 on the lymphocyte and mucosal addressin cell adhesion molecule-1 (MAdCAM-1) on the endothelial cell. A final factor important to the homing of lymphocytes is the chemokines and their receptors. The chemokine milieu of a particular tissue determines which T-helper cell types and other immune cell subsets are recruited.

Answer 147

Antigen uptake, presentation to naïve lymphocytes, costimulation by helper cells, clonal expansion, homing to effector sites, and performance of effector functions.

Answer 148

Most antigen uptake occurs through the M cells of PPs to DCs and macrophages. These APCs process and present antigen to lymphocytes in the context of MHC II molecules. Enterocytes may also present antigen to T cells. (see Web Figure 270-2).(Web Figure 270-3)

Answer 149

B Cell Responses[248,265,271-275] During B cell development, a switch occurs such that cells only produce a single class of immunoglobulin. The switch is assisted by CD4+ T-helper cells via cytokines such as TGF-β, IL-4, and IFN-γ for IgA, IgE, and IgG production, respectively. After class switching, B cells undergo further expansion then traffic to effector sites to differentiate into plasma cells.

Answer 150

IgA synthesis predominates in the healthy intestinal mucosa.The main function of secretory IgA (SIgA) is immune exclusion; that is, to bind its respective antigen and neutralize it. This helps maintain tolerance and protects the mucosa from antigen invasion. Deficiency of SIgA could predispose to intestinal disease.

Answer 151

Responses to parasites also occur through generation of antigen-specific plasma cells in MLNs, producing IgE that binds to the FcϵRI on mucosal MCs. When subsequently exposed to antigen, MC degranulation occurs, and the parasite is expelled. Inappropriate IgE responses can also be generated, providing a mechanism for food allergy.

Answer 152

The main function of cytotoxic lymphocytes in the SI mucosa is to remove tumor cells or cells infected with intracellular bacteria, viruses, or parasites. CD8+ alpha/beta T cells are the main cytotoxic cells, but CD4+ cells γ/δ IELs can participate in cytotoxicity.

Answer 153

the type of response depends on the context in which the antigen is presented.

Answer 154

Enterobacteriaceae Escherichia coli and Clostridium spp

Answer 155

Although epithelial PPRs recognize PAMPs shared by both commensals and pathogens (see Figure 270-2), the GALT remains unresponsive in health. A key downregulatory mechanism is relocation of TLR2 and TLR4 to intracellular and basolateral membrane locations in response to stimulation by bacterial PAMPs. TLR5 is also only found on the basolateral membrane. This prevents activation of the immune system by luminal commensal bacteria, while still allowing a response to pathogens expressing LPS, flagellin, and so on, whenever they breach the epithelial barrier. In addition, intracellular TLR antagonists, toll-interacting protein (TOLLIP) and peroxisome proliferator–activated receptor-γ (PPAR-γ) are expressed by enterocytes in response to stimulation by luminal bacteria and tend to inhibit any TLR stimulation. TOLLIP prevents the activation of the proinflammatory nuclear transcription factor NF-κB, which is also directly inhibited by PPAR-γ.

Answer 156

When the mucosa is invaded by a pathogen or toxin, cell damage leads to the release of “danger signals” such as inflammatory mediators (prostaglandins, leukotrienes), proinflammatory cytokines (IL-1, IL-6, TNF-α), and chemokines (IL-8). Intracellular stimulation of TLRs leads to activation of NF-κB and consequent expression of TNF-α. In this altered environment, the nature of the immune response generated changes from tolerance to an active immune response.

Answer 157

This active response can be either Th1 dominated (e.g., cytotoxicity and IgG responses) or Th2 dominated (i.e., IgE responses), and aimed at eliminating the pathogen completely, although the potential for bystander damage to host cells is great.

Answer 158

If the antigenic challenge is contained, the danger signals diminish, the mucosa enters a repair phase, and the normal “tolerogenic” environment returns. However, if the danger persists, either because the mucosal barrier remains breached and the pathogenic insult continues unabated, or because of an inherent abnormality in the GALT, a state of chronic inflammation ensues. This may also lead to a breakdown in tolerance to harmless environmental antigens (food components and commensal bacteria) and inflammation. Upregulation of TLRs in intestinal inflammation has, as could be predicted, been demonstrated.

Answer 159

Polymorphisms in TLR and NOD expression may provide the genetic basis for differences in responses to commensal bacteria that drive idiopathic inflammatory bowel disease (IBD). Chronic inflammation ultimately leads to histopathologic changes, which are likely to be similar regardless of the inciting cause. Furthermore it has been hypothesized that chronic stimulation of lymphocytes in genetically predisposed patients may ultimately result in expansion of a malignant clone of T lymphocytes, and mucosal lymphosarcoma may develop.

Answer 160

Rapid waves of contractions are caused by ischemia and enterotoxigenic diarrhea. In malabsorption, unabsorbed solutes retain fluid osmotically, causing distension and hypermotility. Hyperthyroidism decreases transit time in cats and causes diarrhea. However, in most instances diarrhea is actually associated with intestinal hypomotility.

Answer 161

The presence of unabsorbed food, especially fat, in the distal SI reflexly inhibits gastric emptying by neurohormonal mechanisms. This “ileal brake” mechanism may be the cause of the delayed gastric emptying typically seen in malabsorption in the absence of gastric disease. Decreased peristalsis delays transit, manifesting clinically as adynamic ileus, a transient and reversible functional obstruction of the intestine with a number of causes. In enteric viral infections, for example, ileus is common, promoting further diarrhea as stasis allows bacterial fermentation. Hypomotility and constipation are expected with hypothyroidism, but occasionally antibiotic-responsive diarrhea is found. (Box 270-3)

Answer 162

Lack of pancreatic enzymes in exocrine pancreatic insufficiency (EPI), increased destruction of enzymes by acid hypersecretion (e.g., Zollinger-Ellison syndrome), and SIBO result in failure of digestion. Interruption of enterohepatic circulation and lack of bile salt micelles result in fat malabsorption if there is significant hepatic dysfunction, bacterial deconjugation of lumenal bile salts, or ileal disease. Surgical resection of the ileum, such as with ileocolic intussusception, and IBD affecting the distal SI cause both bile salt and cobalamin malabsorption.

Answer 163

Villus Atrophy Villus atrophy causes loss of intestinal surface area and results in fat malabsorption. Also, carrier-mediated uptake of carbohydrate and protein digestion products is rate-limited, because there are finite numbers of nutrient transporters.

Answer 164

Atrophy is caused either by a decrease in the production of enterocytes or an increase in the rate of enterocyte loss.

Answer 165

Infectious agents that damage enterocytes may infect the villus tip (e.g., rotavirus) or midvillus (e.g., coronavirus), causing cell loss and a mild to moderate diarrhea.

Answer 166

Cytotoxic drugs, such as vincristine, and parvovirus infection, which cause crypt arrest and destruction respectively, can be devastating, causing complete villus and crypt collapse and severe diarrhea. Assuming some stem cells survive the insult, regeneration is possible, but it is likely to take several days.

Answer 167

A persistently increased rate of enterocyte loss through immune-mediated mechanisms results in a compensatory increase in the crypt cell proliferation rate, and yet if the cell loss is matched by the increased proliferation, villus height does not decrease. However, a significant functional effect is still exerted on the digestive and absorptive ability of the SI, because prematurely lost mature enterocytes are replaced by immature, suboptimally functioning enterocytes.

Answer 168

If enterocyte loss outpaces increased proliferation, villus atrophy will result, but if the initiating cause can be removed, the atrophy is completely reversible.

Answer 169

Damage to brush-border proteins or interference with enterocyte function by bacterial toxins can occur without histologic damage. Malnutrition and ischemia also impair function and increase epithelial permeability.

Answer 170

The MVM is obviously damaged when overt histologic villus damage occurs, but even without light microscopic changes, massive impairment of mucosal function can occur if the microvilli are damaged. Damage caused by enteropathogenic E. coli infection or lectins results in loss of surface area, brush-border enzymes, and carriers. Subtle but specific damage occurs in SIBO as anaerobes degrade membrane glycoproteins and release brush-border enzymes.

Answer 171

Primary brush-border membrane diseases are biochemical abnormalities that occur in the absence of histologic damage. Relative lactase deficiency does occur, particularly in cats. The mechanism of cobalamin deficiency seen in Shar-Peis has not been elucidated yet, but defects in ileal cobalamin–intrinsic factor complex uptake, due to a lack of expression of the receptor molecule cubilin, occur in Collies, Beagles, and Giant Schnauzers. Cobalamin deficiency causes methylmalonic aciduria, and signs include inappetence, failure to thrive, hepatoencephalopathy, neutropenia, and anemia.

Answer 172

Epithelial integrity is crucial in maintaining oral tolerance and excluding pathogens. Natural causes of decreased barrier function include luminal aggressive factors and endogenous inflammatory mediators. Barrier damage may lead to entry of antigens, subsequent allergic and/or inflammatory reactions, and even translocation of bacteria into the circulation. Noradrenaline and IFN-γ, naturally increased by stress, alter enterocyte tight-junction permeability, permitting invasion by Campylobacter. Leakage of protein-rich tissue fluid can lead to a protein-losing enteropathy (PLE).

Answer 173

Sensitization of a patient to a dietary antigen may provoke an IgE-mediated allergic reaction when the animal is next exposed. The release of numerous mast cell mediators may have remote effects, such as pruritus and urticaria; generalized systemic effects, such as anaphylaxis; or only local effects on the intestine. They induce rapid changes in absorption and secretion, mucus secretion, epithelial and endothelial permeability, and gut motility, causing vomiting and diarrhea

Answer 174

Various disruptions of the mucosal immune system lead to chronic inflammation, the end results of which are histologically similar. The disruptions are usually induced in one of three ways: 1) through disruption of the endogenous microflora, 2) through interference with the mucosal barrier, 3) or through dysregulation of the mucosal immune system.

Answer 175

Inflammation causes increased expression of MHC II molecules and activation of both lymphocytes and endothelial cells. Extracellular proteolysis by matrix metalloproteinases leads to architectural changes.

Answer 176

Neoplasia Diffuse tumors that infiltrate the mucosa, such as lymphosarcoma, cause diarrhea. Malignant cells may simply obstruct blood and lymphatic flow, but also enterocyte function is likely to be impaired, or the mucosa may be ulcerated because of ischemia. Solitary tumors can cause diarrhea, probably through the effects of partial obstruction, stasis of ingesta, and secondary bacterial overgrowth. More typically they cause signs of intestinal obstruction: vomiting, abdominal pain, and absence of feces in addition to bleeding, cancer-associated anorexia, and weight loss. Peritonitis may occur if the integrity of the bowel wall is compromised. Cutaneous MC tumors may cause duodenal perforation through histamine-mediated gastric acid hypersecretion.

Answer 177

Nutrient Delivery Failure After absorption, nutrients are delivered to the body via blood and lymph; only lymphatic diseases are described in animals' intestines. Primary lymphatic dilatation and dysfunction (lymphangiectasia) that causes malabsorption may be idiopathic or may be associated with lymphangitis. Secondary lymphangiectasia is seen with lymphatic obstruction.

Answer 178

Diarrhea is an increase in fecal mass caused by an increase in fecal water and/or solid content. It is typically accompanied by an increase in frequency, fluidity, and/or volume of feces. Yet the absence of recognizable diarrhea does not preclude the possibility of SI disease; other signs may occur.

Answer 179

Diarrhea can be classified into categories that are not necessarily mutually exclusive (Box 270-4). The mechanistic approach to the genesis of diarrhea is simple: 1. permeability diarrhea is due to inflammation or neoplastic infiltration causing exudation, and 2. secretory diarrhea is caused by chemical toxins and bacterial toxins (Box 270-5). 3. osmotic diarrhea (most SI diseases have a component of this) 4. even in a situation as simple as lactase deficiency, mixed mechanisms occur (Figure 270-3)

Answer 180

Bacterial fermentation of unabsorbed solutes is often a complicating factor in malabsorption. The fecal pH is often low because of the production of volatile fatty acids, and some products (hydroxylated fatty acids, unconjugated bile acids) cause colonic secretion; signs of large-intestinal diarrhea frequently accompany prolonged SI disease.

Answer 181

Malabsorption Failure of food assimilation is sometimes classified as primary failure to digest (maldigestion) or primary failure to absorb (malabsorption). However, such a classification is misleading, because failure of absorption is an inevitable consequence of failure to digest. The preferred use of the term malabsorption is to describe defective absorption of a dietary constituent resulting from interference with the digestive and/or absorptive processing of that molecule.

Answer 182

The site of the primary abnormality may be found in the luminal, mucosal, or transport phases (Table 270-1). The clinical manifestations of malabsorption—namely diarrhea, weight loss, and altered appetite (polyphagia, coprophagia, pica)—are largely a result of the lack of nutrient uptake and the losses in feces. Polydipsia may be a peculiar manifestation of excessive appetite. The reserve capacity of the distal SI and colon may prevent overt diarrhea despite significant malabsorption and weight loss. Animals are often systemically healthy and have an increased appetite, unless an underlying neoplastic or severe inflammatory condition is present. Only when the patient is quite malnourished or develops hypoproteinemia does it appear ill.

Answer 183

Melena[385-397] The presence of dark, tarry, oxidized blood in feces, a condition called melena, reflects either swallowed blood or generalized or localized GI bleeding proximal to the large intestine (Table 270-2; see Chapter 49). It is estimated that the loss of 350 to 500 mg/kg of hemoglobin into the GI tract is required for melena to be visible. As a caveat, medication with ferrous sulfate, or bismuth suspensions such as Pepto-Bismol, also can impart a black color to feces. The presence of microcytosis and hypochromia with or without thrombocytosis is suggestive of iron deficiency secondary to chronic blood loss. An increased blood urea to creatinine ratio, from bacterial digestion of blood, provides supporting evidence. Hypoproteinemia may indicate blood loss or a PLE.

Answer 184

To rule out bleeding diatheses; ingestion of blood from other lesions, such as oral masses; toxicity, as with nonsteroidal antiinflammatory drugs (NSAIDs); or underlying metabolic disorders, such as hypoadrenocorticism, before pursuing primary GI causes.

Answer 185

The abdominal rumbling noise caused by the propulsion of gas through the GI tract. Swallowed air and bacterial fermentation of ingesta are the main causes of borborygmi and flatulence and often result in an offensive odor.

Answer 186

Feeding a diet that is highly digestible with a low fiber content leaves little material for bacterial fermentation and can effect a cure in some cases. If borborygmi or flatulence continue despite dietary modification or addition of adsorbents, the animal may be excessively aerophagic or may have malabsorption.

Answer 187

malabsorption, and the diagnostic approach is the same as for chronic diarrhea. However, malabsorption causing weight loss does not invariably cause diarrhea.

Answer 188

Inflammation Lymphangiectasia Neoplasia Infectious Gastrointestinal hemorrhage Endoparasites Structural Table 270-3 Hypoproteinemia associated with GI disease is much less common in cats, and most often accompanies GI lymphoma, but infrequently results in ascites.

Answer 189

Lymphocytic-plasmacytic, eosinophilic, granulomatous Primary lymphatic disorder, venous hypertension (e.g., right heart failure, hepatic cirrhosis) Lymphosarcoma Parvovirus, salmonellosis, histoplasmosis, phycomycosis Hemorrhagic gastroenteritis, neoplasia, ulceration Giardia, Ancylostoma spp. Intussusception Table 270-3

Answer 190

The Basenji, Lundehund, Soft-Coated Wheaten Terrier, Yorkshire Terrier, and Shar-Pei.

Answer 191

Weight loss, diarrhea, vomiting, melena, edema, ascites, pleural effusion. Diarrhea is not invariably present, particularly with lymphangiectasia and focal intestinal neoplasia. Thromboembolism secondary to hypoproteinemia is a feature of some cases of PLE

Answer 192

Serum concentrations of both albumin and globulin are reduced in most patients with PLE. Renal and hepatic causes of hypoalbuminemia are ruled out by assay of serum bile acids and urinary protein loss, respectively. Hypocholesterolemia and lymphopenia are common in PLE. Hypocalcemia and hypomagnesemia are also reported. Measurement of fecal loss of alpha1-protease inhibitor may be a sensitive test for PLE.

Answer 193

Colloid support or plasma transfusion may be indicated during the perioperative period when collecting biopsy specimens, and diuretics may reduce ascites. Spironolactone may be more effective than furosemide for treating ascites. Specific treatments are discussed later.

Answer 194

SI disease, especially salmonellosis and whipworm infection

Answer 195

Maybe not: In dogs and cats, secretory diarrhea is less common, the resultant increased volumes of diarrhea may be cosmetically unacceptable, and the presence of vomiting may preclude this approach.

Answer 196

Bismuth subsalicylate, kaolin-pectin, montmorillonite (a refined form of kaolin), activated charcoal and magnesium, and aluminum and barium products are often administered in acute diarrhea to bind bacteria and their toxins and to protect the intestinal mucosa. They also bind water and may be antisecretory. Therapy should not exceed 3 days if there is no improvement.

Answer 197

Anticholinergics and opiates or opioids (loperamide, diphenoxylate) are indicated for the short-term symptomatic management of acute diarrhea in dogs; anticholinergic agents can potentiate ileus and are not recommended. Opiate analgesics stimulate segmental motility, thereby slowing transit, and also decrease intestinal secretion and promote absorption. They are contraindicated in cases involving obstruction or an infectious etiology, and loperamide may have central nervous system (CNS) side effects in dogs with the multidrug resistance 1 (MDR-1) gene mutation.

Answer 198

Only in animals with SI disease with a confirmed bacterial or protozoal infection, or in those in which a breach of intestinal barrier integrity is suspected from evidence of GI bleeding and, consequently, which are at risk of sepsis. Leukopenia, neutrophilia, pyrexia, the presence of blood in the feces, and shock all are potential indications for prophylactic antibiotics in animals with diarrhea.

Answer 199

Include ampicillin or a cephalosporin effective against gram-positive and some gram-negative and anaerobic bacteria. If systemic translocation of enteric bacteria is suspected, antimicrobials effective against anaerobic organisms, such as metronidazole or clindamycin, and an aminoglycoside or a fluoroquinolone effective against “difficult” gram-negative aerobes, are indicated. Intravenous quinolones have been shown to reach therapeutic concentrations in the canine gut lumen and can be effective against enterococci, E. coli, and anaerobes. Aminoglycosides such as gentamicin should not be given until the patient is volume-expanded.

Answer 200

Orally administered living organisms that exert health benefits beyond those of basic nutrition. In addition to direct antagonistic properties against pathogenic bacteria, they modulate mucosal immune responses. In other words, they can switch off expression of TNF-α through NF-κB and alter intestinal permeability.

Answer 201

Hemorrhagic gastroenteritis (HGE) is the name given to a syndrome characterized by acute hemorrhagic diarrhea typically accompanied by marked hemoconcentration and usually seen in small-breed dogs. Its cause is unknown; it may represent an intestinal type 1 hypersensitivity reaction, or it may be the result of C. perfringens enterotoxin production.

Answer 202

Appropriate clinical findings associated with a packed cell volume (PCV) greater than 60%. Total protein is often normal or not as high relative to the PCV, probably because of intestinal plasma loss. Radiographs may demonstrate ileus. The absence of leukopenia and the marked hemoconcentration help distinguish HGE from parvovirus, but pancreatitis needs to be ruled out. Direct evidence of SI clostridial infection is rarely obtained.

Answer 203

Intravenous crystalloids are essential; some patients become hypoproteinemic and require plasma or colloid support. Parenteral antibiotics are often administered because of potential clostridial infection and the high risk of sepsis.

Answer 204

Parvovirus, Giardia, Tritrichomonas, Salmonella, Campylobacter spp., and some helminths can be significant causes of diarrhea. The importance of coronavirus, C. perfringens, and E. coli as causes of diarrhea has yet to be defined. Trematodes (flukes) are rare in dogs and cats but more likely cause liver disease as well as carrying Neorickettsia. Intesintial myiasis is a very rare problem. Other viruses such as paramyxoviruses, adenoviruses, feline leukemia, and immunodeficiency viruses, which all can cause diarrhea but primarily affect other organ systems.

Answer 205

Intestine (crypt cells) Bone marrow Lymphoid tissues. It causes intestinal crypt necrosis with severe diarrhea, neutropenia, and lymphoid depletion associated with immunosuppression.

Answer 206

Typically occur 4 to 7 days after infection. Anorexia, depression, fever, vomiting, diarrhea (often profuse and hemorrhagic), and dehydration are common. Relative adrenal insufficiency occurs, and hypothermia and disseminated intravascular coagulation (DIC) are terminal events. Puppies younger than 6 weeks usually are protected by maternal antibody, and variation in severity of disease within a litter probably reflects both viral infective load and residual levels of maternal antibody.

Answer 207

Sudden onset of vomiting and diarrhea, especially if they are also depressed, febrile, or leukopenic or if they have been in contact with infected dogs. Leukopenia, often 500 to 2000 white blood cells per microliter, may be detected in up to 65% of field cases and is very suggestive of parvovirus infection. It reflects neutropenia and lymphopenia.

Answer 208

From impaired bone marrow production with concurrent neutrophil loss through the damaged GI tract, and severe neutropenia carries a poorer prognosis. In the absence of leukopenia, clinical signs are indistinguishable from other reasons of acute diarrhea.

Answer 209

Demonstration of CPV-2 virus or viral antigens either in feces or in tissues (e.g., intestine, tongue) postmortem. Fecal ELISA, available as a SNAP test, is most sensitive in the first 10 to 12 days after infection, when virus excretion is greatest, but may cross-react with recently administered vaccine strains. Serotyping by PCR may be helpful in differentiating vaccinal strains. Single anti–CPV antibody determination in serum by hemagglutination inhibition is not useful for diagnosis, and a rising IgG titer by paired serology provides only a retrospective diagnosis.

Answer 210

Its significance as a primary pathogen is unclear. Infected dogs may shed virus intermittently for months after clinical recovery. Antibodies against CCV are present in many healthy and diarrheic dogs, yet severe, naturally occurring disease is reported sporadically. Transmission is by the fecal-oral route, and infection is prevalent, particularly in shelter and laboratory dogs. Most CCV infections are probably subclinical, although severe enteritis may occur in dense populations or with concurrent infections.

Answer 211

Mutate to feline infectious peritonitis virus (FIPV).

Answer 212

Diarrhea and vomiting, and cats have a palpable mass in the colon or ileocecocolic junction. Affected intestine is markedly thickened and nodular, with multifocal pyogranulomas extending through the intestinal wall.

Answer 213

Infection with feline immunodeficiency virus (FIV) is associated with a 10% to 20% incidence of chronic enteritis. Although secondary and opportunistic infections may be responsible for signs, sometimes no other etiologic agent can be identified.

Answer 214

Associated with fatal peracute enterocolitis and lymphocytic ileitis.

Answer 215

Rotaviruses can infect dogs and cats, but infection is so transient that no disease is recognized.

Answer 216

These organisms may also be isolated from healthy animals and from those with chronic diarrhea, so confusion exists about their significance when isolated.

Answer 217

C. jejuni and C. upsaliensis have been associated with intestinal disease in dogs and cats, although experimental infection of dogs causes only transient signs. C. upsaliensis is also the predominant isolate in both clinically healthy dogs and dogs with chronic diarrhea. Thus, many infections are asymptomatic, with carriage rates in healthy dogs and cats up to and over 50% reported; kenneled and younger animals have the highest isolation rates. Clinically significant disease is usually restricted to young, parasitized, or immunocompromised animals and is usually related to sporadic infection. C. jejuni can become enteroinvasive if an animal is stressed, a bacterial behavioral change that is mediated by host-derived norepinephrine and interferon. Canine infection with C. upsaliensis is more common; longitudinal studies show a tendency for the same clonal infection to persist for years, and potentially this organism is actually commensal in dogs although still zoonotic. The presence of slender, seagull-shaped bacteria on a stained fecal smear yields a presumptive diagnosis. only PCR will give reliable species information. Because the organisms are fragile, diagnosis is best made by isolating them from fresh feces. Campylobacter organisms are usually treated with erythromycin.

Answer 218

Four scenarios may follow infection: Transient asymptomatic infection, Acute gastroenteritis, A carrier state, or Bacteremia. Invasion and then translocation from the gut lumen may result in septicemia, endotoxemia, DIC, and death in susceptible animals. Cats with Salmonella infection may show only vague signs (pyrexia, leukocytosis, and conjunctivitis) and no GI signs; but a seasonal, acute, febrile illness with diarrhea, known as songbird fever, has been reported in cats after ingestion of migrating songbirds infected with S. typhimurium.

Answer 219

Diagnosis is based on the isolation of Salmonella organisms from feces or from blood in septicemic patients. Clinicopathologic features are nonspecific: hyperkalemia and hyponatremia (pseudohypoadrenocorticism) may occur. Antibiotic treatment may promote bacterial resistance and a carrier state, so it is not recommended when Salmonella bacteria are isolated from healthy infected animals or stable animals with diarrhea. . In animals with severe hemorrhagic diarrhea, marked depression, shock, persistent pyrexia, or sepsis, parenteral antibiotics need to be given. The choice of antibiotic should be governed by sensitivity testing when possible, but fluoroquinolones appear to be effective against many Salmonella spp.

Answer 220

C. perfringens and other clostridial species are part of the normal flora of dogs and cats but may cause diarrhea as a consequence of enterotoxin production. However, enterotoxin can be detected in the feces of healthy dogs.

Answer 221

C. difficile may also be part of the resident microflora of dogs but can be a hospital-acquired infection. The organism produces two toxins (A and B) and is responsible for antibiotic-associated pseudomembranous colitis in humans. It has been incriminated as a cause of chronic diarrhea in dogs.

Answer 222

E. coli can be a significant cause of acute diarrhea, and some isolates may cause chronic diarrhea. The importance of enteropathogenic (EPEC) and enterotoxigenic (ETEC) E. coli in dogs and cats is gradually being resolved: although many strains are normal commensals, some contain chromosomal and/or plasmid genes that encode for pathogenicity. Enteroadherent E. coli have been reported to cause chronic diarrhea in dogs. Attaching and invasive E. coli are associated with histiocytic ulcerative colitis.

Answer 223

Attachment of ETEC organisms and subsequent release of heat-labile, heat-stable, and Shiga-like toxins may cause acute disease. Permanent attachment of EPEC to the mucosa causes effacement of microvilli and produces profound malabsorption and diarrhea without causing marked changes on light microscopy (Figure 270-10).

Answer 224

Yersinia pseudotuberculosis can be ingested by cats eating infected rodents or birds. The bacteria infect the GI tract, liver, and lymph nodes, causing marked weight loss, diarrhea, anorexia, lethargy, jaundice, and mesenteric lymphadenopathy.

Answer 225

In dogs and cats, Mycobacterium spp. causes multisystemic, granulomatous infections that occasionally involve the GI tract. Cats may develop SI infection with M. bovis from drinking infected cow's milk, an infection associated with vomiting, diarrhea, weight loss, mesenteric lymphadenopathy, and peritonitis. (Dogs more frequently get respiratory infection)

Answer 226

Neorickettsia helminthoeca and Neorickettsia elokominica are found in the metacercaria of the fluke Nanophyetus salmonicola, which is present in salmon in the western regions of the Cascade Mountains from northern California to central Washington, and more recently reported in Brazil. About a week after ingestion of infected salmon by dogs (and coyotes), the rickettsiae emerge from the mature fluke and cause a disease characterized by high fever, HGE, vomiting, lethargy, anorexia, polydipsia, nasal and ocular discharge, and peripheral lymphadenopathy. Mortality is extremely high in untreated patients. The diagnosis is based on a history of ingestion of raw fish in an endemic area, the detection of operculated fluke eggs in feces, and the presence of intracytoplasmic inclusion bodies in macrophages from lymph node aspirates.

Answer 227

Toxic algae can lead to acute gastroenteritis and death. Blue-green algal blooms can synthesize an anticholinesterase that induces vomiting, diarrhea, ataxia, and rapid death in dogs that drink contaminated water. Prototheca spp. are achlorophyllous algae that cause protothecosis.

Answer 228

Intestinal aspergillosis and mucormycosis have been reported in cats. Primary intestinal infection with the aquatic oomycete Pythium spp., or pythiosis, is by far the most common phycomycosis, an infection with a poorly septate mold. Candida spp. are dimorphic fungi that normally inhabit the GI tract, but they can be opportunistic invaders. Pythiosis occurs sporadically throughout the world in tropical and subtropical climates.

Answer 229

cats large intestine.

Answer 230

Isospora spp. are the most common coccidial parasites of dogs (I. canis, I. ohioensis) and cats (I. felis, I. rivolta). Transmission occurs by ingestion of ova or paratenic hosts. Sporozoites are liberated in the SI and enter enterocytes to develop. Infection is rarely associated with clinical signs. Puppies and kittens kept in unhygienic conditions and immunosuppressed animals may develop heavy infestations, which occasionally are associated with mucoid or even bloody diarrhea. The infection is often self-limiting, but sulfadimethoxine or trimethoprim sulfa can be used when signs warrant treatment.

Answer 231

Cryptosporidium parvum, a significant pathogen in humans and calves, is now recognized not to be a single species. Twenty-one C. parvum genotypes are currently recognized and include cat and dog “species,” sometimes termed C. canis and C. felis respectively. C. parvum is an obligate intracellular parasite. Infection may be asymptomatic but has been associated with self-limiting diarrhea in cats, and more rarely in dogs, and with severe hemorrhagic diarrhea in immunocompromised animals and animals with coinfections. Infection is most common in young animals, often with concurrent parasitic infections, but prevalence varies with geography as well. Transmission occurs by the fecal–oral route. Cats shed more frequently than dogs, and excretion can be reactivated by steroid administration or surgical stress. identified by fecal flotation and oil immersion microscopy, direct immunofluorescence, modified acid-fast staining, enzyme immunoassay techniques, or PCR. Organisms may be recognized in intestinal biopsies.

Answer 232

Cats are less commonly infected. The parasite is usually transmitted via the fecal-oral route. Ingested oocysts excyst in the upper SI, and trophozoites attach to the intestinal mucosa from the duodenum to the ileum. After multiplication of trophozoites, oocysts are passed in the feces at 1 to 2 weeks after infection. Most infections are asymptomatic, but signs range from mild, self-limiting, acute diarrhea to severe or chronic small-bowel diarrhea associated with weight loss.

Answer 233

Highly digestible, moderately fat-restricted, lactose-free, gluten-free, not markedly hypertonic, nutritionally balanced, and palatable. Feeding the daily nutritional requirement in divided meals (usually between two and four) reduces the load on a compromised intestine. Feeding more frequently is unnecessary, because gastric emptying imposes natural trickle-feeding of the intestine. Inclusion of moderately fermentable fiber, such as psyllium or ispaghula, is known to promote colonic health. Soluble fiber also promotes small-intestinal health, but fiber can delay intestinal transit, and excess fiber may be contraindicated. Prebiotic supplements such as FOS and mannanoligosaccharides alter the fecal flora, but their effect on the SI flora is limited.

Answer 234

Tylosin, metronidazole, or oxytetracycline are commonly used, but any beneficial effects may go beyond their antibacterial activity, with potential effects on the mucosal immune system.

Answer 235

An adverse reaction to food is a repeatable, unpleasant response to a dietary component that is a manifestation of either an immunologic reaction to a dietary antigen (i.e., a true food allergy) or a nonimmunologic reaction (i.e., an intolerance). Although different pathogenetic mechanisms are responsible, the clinical signs are similar, and the approach to treatment is the same, typically involving exclusion of the offending food component.

Answer 236

Type I (IgE-mediated, immediate), Type II (immune-complex mediated) Type IV (delayed hypersensitivity) reactions. A contemporaneous association between ingestion of a particular food and the onset of signs is suggestive of a type I . Current hypotheses of food allergy propose one or a combination of mechanisms that lead to breakdown of oral tolerance: an inadequate mucosal barrier, abnormal presentation of dietary antigens to the mucosal immune system, or immune system dysregulation as discussed earlier. Concurrent skin and GI signs can occur but have been reported only rarely.

Answer 237

The major sign of food-allergic skin disease is pruritus, which is nonseasonal and has no characteristic distribution, although pedal pruritus, facial pruritus, and otitis externa may be noted.

Answer 238

Vomiting, diarrhea, abdominal pain, flatulence, borborygmi, weight loss, and failure to thrive.. The only reliable way to confirm the presence of dietary sensitivity is a diet trial, but it does not distinguish food intolerance from allergy.

Answer 239

Predictable intolerances occur in any animal after ingestion of a contaminated foodstuff or after consumption of a recognized toxin or excessive amounts of food. In contrast, unpredictable food intolerances, although repeatable in a susceptible individual, are idiosyncratic reactions. Reasons for idiosyncrasies include differences, genetic or otherwise, in intestinal enzyme activities, intestinal permeability, postabsorption metabolism, MC stability, and in the intestinal flora.

Answer 240

Methylxanthines

Answer 241

These adverse reactions are histamine-mediated but arise from nonimmunologic mechanisms. A high histamine concentration may be present naturally in some foods—tuna, mackerel, and some commercial dog foods—or because of histamine-producing bacteria, as in cheese or canned fish contaminated with Proteus or Klebsiella organisms. Some foods, such as shellfish and strawberries, and food additives, such as tartrazine, can cause histamine release from MCs without IgE mediation. This mechanism is well documented in humans but not in small animals.

Answer 242

At weaning, activities of lactase decline, especially in cats, and animals may become lactose intolerant if fed excess milk. If they have underlying SI disease, dairy products should be avoided, as marginal lactase activities will be reduced even further. However, allergy to bovine milk proteins or previously subclinical intestinal disease may also explain adverse reactions to milk.

Answer 243

Vomiting, diarrhea, and abdominal discomfort. However, pruritus and even anaphylaxis are possible if histamine release is involved. Behavioral problems may be diet-responsive through nonimmunologic mechanisms.

Answer 244

Exclusion-diet trials are required to diagnose both food allergy and intolerance but do not distinguish between them.

Answer 245

Traditional Exclusion Diet This diet is composed of single protein and carbohydrate sources. Baby foods are not recommended, particularly in cats, as they may be relatively taurine-deficient and often contain onion powder, which can cause Heinz body anemia. Lamb or chicken with rice have been the standard choices, but given the increased diversity of commercial pet foods, these components are not always appropriate. Hydrolyzed protein diets, usually based on either chicken or soy protein, are an alternative exclusion diet and are now readily available. In principle, the hydrolytic process splits proteins into components of a molecular weight below that which would be expected to elicit an immune response. To completely abolish all antigenicity, peptides need to be less than 1 kD—but at that size, they have a bitter taste. At the size achieved in palatable hydrolyzed diets (7 to 10 kD), proteins are still potentially antigenic but are too small to be able to cross-link IgE molecules on MCs, and type I reactions are abolished. However, type IV reactions are still possible. Once remission is achieved, the animal should be challenged with the original diet to demonstrate relapse and confirm the diagnosis. Some animals may not relapse, perhaps because the mucosal barrier has been restored and further reactions are prevented. However, some clients refuse challenge, particularly if relapse is likely to bring recurrence of diarrhea.

Answer 246

Intestinal disease induced by the presence of dietary wheat gluten has been clearly documented in Irish Setters. . In Irish Setters, gluten-sensitive enteropathy (GSE) is a familial condition with an autosomal recessive mode of inheritance. . The disease may affect other dog breeds but has not been reported in cats. Gluten sensitivity has been suggested in Soft-Coated Wheaten Terriers with PLE and nephropathy. Ingested wheat protein, gluten, is either directly toxic to the intestinal mucosa or induces an adverse immune reaction. Affected Irish Setters typically present with poor weight gain and chronic, intermittent diarrhea after weaning

Answer 247

...an increase in the absolute number of bacteria in the upper SI during the fasted state. Normally the bacterial population of the SI is controlled by a number of mechanisms. Overgrowth is the uncontrolled proliferation of these bacteria, and in humans, it occurs secondary to disorders that interfere with these control mechanisms

Answer 248

Historically, the term idiopathic SIBO has been used to describe an antibiotic-responsive condition of large-breed dogs, especially German Shepherds, for which no underlying cause could be found. Response to a range of antibiotics is usually seen, but an enteropathy responsive only to tylosin has been reported. However, given concerns whether a true increase in bacterial numbers exists in idiopathic canine cases, the alternative name, antibiotic-responsive diarrhea (ARD), has been adopted. In dogs, SIBO is best considered a clinical sign or a secondary pathogenetic mechanism. Although cats might feasibly suffer from secondary SIBO, an idiopathic antibiotic-responsive condition similar to that seen in dogs has not been documented.

Answer 249

Subsequent studies using improved techniques have demonstrated that a total count ≥105 CFU/mL is commonly found in asymptomatic dogs. Therefore, although a true SIBO may exist secondary to various conditions, defining the idiopathic disease as SIBO based on the original numeric cutoff is flawed. In this chapter, cases with a documented underlying cause are defined as secondary SIBO, and the term idiopathic ARD is used for idiopathic antibiotic-responsive conditions.

Answer 250

Malabsorption and diarrhea through several mechanisms: competition for nutrients, metabolism of nutrients to create products that provoke diarrhea (e.g., deconjugated bile salts and hydroxylated fatty acids), and direct damage the mucosal brush border. However, these mechanisms may not be relevant if there are not increased numbers.

Answer 251

(1) diseases that result in excess substrate in the intestinal lumen, (2) diseases that affect the clearance of bacteria (3) morphologic or functional derangement of the mucosa (see Box 270-12).

Answer 252

Another hypothesized mechanism is SIgA deficiency. A selective SIgA deficiency in the German Shepherd breed may exist. Affected German Shepherds may have defective SIgA production although mucosal IgA+ plasma cell numbers are either normal or even increased.

Answer 253

Dogs with ARD have increased LP CD4+ T cells and increased expression of certain cytokines, suggesting immune dysregulation and perhaps a loss of tolerance toward endogenous bacteria. Such a hypothesis is supported by the fact that antibacterials lead to resolution of clinical signs and decreased cytokine expression but not to a decline in bacterial numbers. And the fact that the most effective antibacterials are also those with immune-modulating properties (e.g., oxytetracycline, metronidazole, tylosin) may also support this hypothesis.

Answer 254

Chronic intermittent diarrhea accompanied by weight loss and/or stunting. Intermittent, watery diarrhea, often associated with excessive gas production manifested as borborygmi and flatus, is seen most frequently. However, vomiting and signs of colitis are reported, and occasionally dogs are stunted yet do not have overt diarrhea. Appetite is variable; most affected dogs have polyphagia, pica, and/or coprophagia, but a few are anorectic, perhaps associated with acquired cobalamin deficiency. A positive response to antibiotics is expected, and the condition may deteriorate if corticosteroids are given. The major differential diagnoses are EPI and IBD, both of which are common in the breed.

Answer 255

Serum Folate and Cobalamin Concentrations[559],[1224] Bacteria can synthesize folate and bind cobalamin, preventing its absorption. Therefore SIBO would be predicted to be associated with increased serum folate and/or decreased cobalamin concentrations, as seen in humans with SIBO secondary to a blind loop. Yet studies have demonstrated that these tests are of limited value in the diagnosis of idiopathic ARD. Alterations of serum folate and cobalamin noted in EPI may reflect pancreatic dysfunction rather than secondary SIBO. Although available these tests are generally unhelpful in the diagnosis of idiopathic ARD and are not recommended.

Answer 256

The response to empirical therapy. However, a response to antibacterials is not specific and indeed may be beneficial in IBD, infectious diarrhea, and even a range of nonenteric diseases, such a portovascular anomalies. Furthermore, response to antibiotic therapy does not discriminate idiopathic ARD from secondary SIBO. Therefore an empirical response to antibiotics is valid only after thorough diagnostic investigations have eliminated other possible causes.

Answer 257

(1) a positive clinical response to an antibiotic trial; (2) relapse of signs upon withdrawal of antibiotics; (3) remission on reintroduction of antibiotics; and (4) elimination of other causes based on the results of other diagnostic tests and histopathologic assessment.

Answer 258

No cure is available for idiopathic ARD, but signs can be controlled with antibacterials. A broad-spectrum antibiotic is indicated; suitable choices include oxytetracycline, metronidazole, and tyrosine. Whichever antibacterial is chosen, a 4- to 6-week course is given initially. A highly digestible, low-fat diet is recommended to reduce the substrate available for bacterial use. Finally, if low cobalamin concentrations occur, parenteral cobalamin therapy is warranted.

Answer 259

Although antibacterial therapy improves clinical signs, appropriate treatment for the underlying condition is preferable. For EPI, pancreatic enzyme supplementation can reduce bacterial numbers, because exogenous proteases have antibacterial properties.

Answer 260

A disorder of the SI characterized by persistent or recurrent GI signs and histologic evidence of intestinal inflammation.

Answer 261

Lymphocytic-plasmacytic enteritis (LPE) is the most common form reported; eosinophilic gastroenteritis (EGE) is less common; and granulomatous enteritis is rare. Neutrophilic infiltration is a feature of human IBD but is sometimes seen in feline and rarely in canine idiopathic IBD.

Answer 262

Shar-Peis often have a severe LPE with hypoproteinemia and extremely low serum cobalamin concentrations. In cats an association, called triaditis, exists between IBD, lymphocytic cholangitis, and chronic pancreatitis.

Answer 263

Severe disease is associated with weight loss and PLE, with consequent hypoproteinemia and ascites. Appetite is variable; polyphagia may be present in the face of significant weight loss, whereas anorexia occurs with severe inflammation. Milder inflammation may not affect appetite, although postprandial pain can be significant even without other signs.

Answer 264

The breakdown of immunologic tolerance to luminal antigens (bacteria and dietary components) is thought to be critical, perhaps resulting from disruption of the mucosal barrier, dysregulation of the immune system, or disturbances in the microbiome. Antigens derived from the endogenous microflora are likely to be important in disease pathogenesis, and a potential role for diet-related factors is suggested by the clinical benefit of dietary therapy in some cases of IBD. Undiagnosed infection remains a possibility, considering the recent identification of attaching and invading E. coli in histiocytic ulcerative colitis of Boxers Toxoplasmosis can also be associated with SI inflammation. Genetic factors are likely to contribute to the pathogenesis of IBD: Genetic polymorphisms in either NOD2 or TLRs may occur in certain dog breeds.

Answer 265

No pathognomonic changes are seen in IBD, but diseases of other organ systems should be recognized and excluded. In addition, hypocholesterolemia suggesting malabsorption, hypocalcemia, and hypomagnesemia may also be found. Hypoalbuminemia and hypoglobulinemia are characteristic of PLE, and hypoalbuminemia correlates with a poorer prognosis. Intestinal inflammation in dogs may cause a “reactive hepatopathy,” with mild elevations in liver enzymes. In contrast, because of their shorter half-lives in cats, enzyme increases are more likely to be the result of primary liver disease.

Answer 266

Serum concentrations of both these vitamins are affected by intestinal absorption, therefore inflammation can result in subnormal folate concentrations (proximal inflammation), cobalamin concentrations (distal inflammation), or both (diffuse inflammation). The degree of hypocobalaminemia in IBD correlates with the degree of histologic damage and a poorer prognosis. Although cobalamin deficiency is not pathognomonic for IBD, it does require therapeutic correction, as it has systemic metabolic consequences.

Answer 267

The diets recommended for patients with IBD are antigen-limited and based on a highly digestible, single-source protein preparation. An easily digestible diet decreases the intestinal antigenic load and thus may reduce mucosal inflammation. Such diets may also help resolve any secondary sensitivities to dietary components that may have arisen from disruption of the mucosal barrier. Hydrolyzed diets may play a useful role in this regard. Well-cooked rice is the preferred carbohydrate source because of its high digestibility, but potatoes, cornstarch, and tapioca are also gluten-free. Fat restriction reduces clinical signs associated with fat malabsorption. Supplementation with oral folate and parenteral cobalamin is indicated if serum concentrations are subnormal. Modulation of the enteric flora with probiotics or prebiotics may have benefits in targeting the pathogenesis of IBD

Answer 268

Oxytetracycline and tyrosine, may also have immunomodulatory effects and some efficacy.

Answer 269

In dogs, glucocorticoids are used most frequently, and prednisone and prednisolone are the drugs of choice. Dexamethasone should be avoided, because in some species, it is deleterious to brush-border enzyme expression

Answer 270

The response to treatment in feline IBD appears better, and remission is often prolonged; metronidazole as a sole therapy in milder cases can be successful, and cats are more resistant to the metabolic effects of chronic steroid usage. Indeed prolonged survival has also been seen in feline small-cell alimentary with simple prednisolone and chlorambucil therapy.

Answer 271

Lymphocytic-Plasmacytic Enteritis (LPE) Lymphocytes and plasma cells

Answer 272

Alterations in immune cell populations in canine LPE include increases in LP T cells (especially CD4+ cells), IgG+ plasma cells, macrophages, and granulocytes. Marked alterations in cytokine patterns also occur in canine LPE, with increased expression of Th1 (IL-2, IL-12, and IFN-γ), Th2 (IL-5), proinflammatory (TNF-α), and immunoregulatory (TGF-β) cytokines, confirming that the mucosal immune response is upregulated in canine IBD. Increased concentrations of acute-phase proteins (e.g., C-reactive protein), which normalize after treatment, indicate an inflammatory response.

Answer 273

Clinical signs of LPE, including chronic diarrhea and weight loss, are not pathognomonic. Chronic vomiting may be the predominant sign, especially in cats. PLE, with or without concurrent protein-losing nephropathy, has also been described in Soft-Coated Wheaten Terriers.

Answer 274

A severe, hereditary form of LPE has been well characterized in Basenjis. Affected Basenjis often have hyperglobulinemia but not alpha heavy-chain disease, although they may be predisposed to lymphoma. The intestinal lesions are characterized by increases in CD4+ and CD8+ T cells.

Answer 275

Signs of PLE tend to develop at a younger age than PLN. Clinical signs of the PLE include vomiting, diarrhea, weight loss, and pleural and peritoneal effusions. Occasionally, thromboembolic disease may occur.

Answer 276

In most dogs with PLE, preliminary lab investigations demonstrate panhypoproteinemia and hypocholesterolemia. In contrast, hypoalbuminemia without hypoglobulinemia, hypercholesterolemia, proteinuria, and ultimately azotemia are seen if only PLN has developed. Intestinal biopsy reveals evidence of intestinal inflammation, villus blunting, and epithelial erosions, as well as dilated lymphatics and lipogranulomatous lymphangitis. The treatment for PLE/PLN is similar to that described for general IBD, but the prognosis is usually poorer.

Answer 277

It frequently also involves the stomach and/or colon in EGE and/or colitis. Segmental EE has also been reported.

Answer 278

variable mucosal architectural disturbances, such as villus atrophy, are present in conjunction with a mixed infiltrate of inflammatory cells in which eosinophils predominate Presence of eosinophils between epithelial cells of the villus and crypt, which suggests transepithelial migration. Nevertheless, the number of mucosal eosinophils can vary markedly in normal dogs, and therefore this condition may be overdiagnosed. As with other forms of IBD, a diagnosis of EE should be made only after other causes of eosinophilic inflammation have been eliminated.

Answer 279

Vomiting, SI diarrhea, and LI diarrhea. Mucosal erosion or ulceration may occur more frequently in EE than in other forms of IBD, therefore hematemesis, melena, or hematochezia may be seen. Severe EE has been associated with PLE and, rarely, with spontaneous perforation of the GI tract.

Answer 280

Dietary sensitivity, endoparasitism, or visceral larva migrans, or it may be idiopathic. The eosinophil infiltration is likely to be the result of local and systemic production of cytokines and chemokines, such as IL-5, and members of the eotaxin family. These mediators may be produced by the Th2 subset of CD4+ T cells.

Answer 281

Parasitism, hypoadrenocorticism, allergic cutaneous or respiratory disease, and MC neoplasia.

Answer 282

Conventional therapy is not usually effective, and the prognosis is guarded, although a combination of surgical resection and antiinflammatory treatment was reported to be successful in one case. In cats, a pyogranulomatous transmural inflammation has been associated with FIPV infection.

Answer 283

Marked dilatation and dysfunction of intestinal lymphatics. Abnormal lymphatics leak protein-rich lymph into the intestinal lumen, ultimately causing PLE and hypoproteinemia. Lymphangiectasia may be a primary disorder, or it can develop secondary to lymphatic obstruction.

Answer 284

Primary lymphangiectasia is usually limited to the intestine, although it may be part of a more widespread lymphatic abnormality involving, for example, chylothorax. It is considered congenital, although clinical signs are not usually present from birth. Mucosal inflammation and lipogranulomatous lymphangitis are sometimes reported in association with lymphangiectasia, and some authors consider this condition to be a variant of idiopathic IBD. However, the lymphatic abnormalities predominate and involve the full intestinal wall thickness, while in most cases of idiopathic IBD, only mild lacteal dilatation is seen (Figure 270-12).

Answer 285

However, the primary event is unclear: leakage of lymph could cause inflammation and granuloma formation, or lymphangitis could cause lymphatic obstruction. The development of associated lipogranulomatous lymphangitis, superimposed on the congenital abnormalities, may be one reason for late onset and progression. The disease is most commonly seen in small terrier breeds (e.g., Yorkshire, Maltese), Rottweilers, and in the Norwegian Lundehund

Answer 286

The clinical manifestations of lymphangiectasia are largely attributable to the effects of the enteric loss of lymph. Other intestinal functions remain intact, and hypoproteinemia may be present without diarrhea.

Answer 287

Diarrhea, steatorrhea, profound weight loss, and polyphagia are more typical, and vomiting, lethargy, and anorexia are seen occasionally. Signs may be insidious in onset and have an intermittent or fluctuating pattern. Ascites or subcutaneous edema may develop secondary to hypoproteinemia.

Answer 288

Ascitic fluid is usually a pure transudate, but if right heart failure causes secondary lymphangiectasia, a modified transudate develops through portal hypertension. Chylous ascites can occur if the cisterna chyli is abnormal or abdominal lymphatics are obstructed by abdominal neoplasia, such as pheochromocytoma. Lymphangiectasia has been associated with granulomatous hepatopathy and, in Lundehunds, with chronic gastritis and gastric carcinoma.

Answer 289

Given that lymph is rich in lipoproteins and lymphocytes, laboratory analysis often shows panhypoproteinemia, hypocholesterolemia, and lymphopenia. Hypocalcemia and hypomagnesemia have been reported. The hypocalcemia is the result not only of hypoalbuminemia and lack of the protein-bound fraction but also ionized hypocalcemia. Therefore other mechanisms, including vitamin D and calcium malabsorption, may be involved.

Answer 290

“Ballooning dilatation” of lymphatics, not only in the mucosa but also in the submucosa. True lymphangiectasia must be distinguished both from normal postprandial dilatation of lacteals and from the secondary lacteal dilatation occasionally noted IBD

Answer 291

decrease the enteric loss of protein and resolve associated inflammation to halt diarrhea, while controlling any edema or effusions. Dietary manipulation and glucocorticoids are the most important treatments.

Answer 292

The ideal diet for cases of lymphangiectasia is markedly fat restricted, calorie dense, and highly digestible. Weight-reduction diets, although low in fat, are inappropriate, because patients require a high level of nutrition. Supplementation with fat-soluble vitamins is advised. There are anecdotal reports of improvement with glutamine supplementation and cyclosporin treatment. Glucocorticoid therapy (prednisolone) may be beneficial in some cases, especially if associated lymphangitis, lipogranulomas, and/or a lymphocytic-plasmacytic infiltrate are present in the LP. Unfortunately, not all cases respond to such therapy. The use of antimicrobials, such as tylosin or metronidazole, has not shown any obvious success. Diuretics are indicated in the management of effusions, and combinations of diuretics are preferred (e.g., furosemide and spironolactone). The response to treatment is unpredictable, but cessation of clinical signs may be achieved temporarily, with remissions of months to several years. However, the overall long-term prognosis is poor, and patients ultimately succumb to severe malnutrition, incapacitating effusions, and intractable diarrhea.

Answer 293

MISCELLANEOUS CAUSES OF PROTEIN-LOSING ENTEROPATHY Common causes of PLE include lymphoma, IBD, and lymphangiectasia. However, there have also been recent reports of PLE associated with intestinal crypt lesions without evidence of lymphangiectasia or inflammation in most cases. “Crypt Disease” A low frequency of crypt abscessation is probably normal, but increased crypt pathology has been associated with PLE. The underlying etiology of such lesions is not known. Response to therapy with antibacterials and immunosuppressive medication is variable; some dogs deteriorate suddenly, and they can die from thromboembolic disease.

Answer 294

Lymphomas, adenocarcinomas, and MC tumors are the most common GI tumors in cats, with lymphoma predominating

Answer 295

Adenocarcinomas, smooth-muscle tumors, and other stromal cell tumors are more common in dogs.

Answer 296

Intestinal Lymphoma (Lymphosarcoma) Alimentary lymphoma (AL) is characterized by mucosal, submucosal, and/or epithelial infiltration of neoplastic lymphocytes, invading the intestine in either a diffuse or a focal manner. Focal infiltration can be nodular, plaquelike, or circumferential, but diffuse is more common. Focal forms may cause obstruction; diffuse infiltration results in malabsorption and often PLE in dogs. Most affected cats test negative for FeLV at the time of diagnosis, and AL has become the most common form of lymphoma, following the decline of FeLV infection. Progression from LPE to AL may occur: chronic antigenic stimulation in genetically predisposed patients may stimulate transformation of T cells and progression to low-grade AL.

Answer 297

Clinical signs of hypoproteinemia may develop if diffuse AL results in severe PLE. As well as the expected problems of malabsorption and PLE, intestinal perforation and peritonitis can occur. Involvement of other sites such as the spleen and pancreas may occur.

Answer 298

Anemia, characterized as either normocytic-normochromic nonregenerative or microcytic and hypochromic, is either anemia of chronic disease or of chronic blood loss. A secondary Coombs’ positive anemia sometimes occurs. Neutrophilia may be evident, and occasionally paraneoplastic hypereosinophilia is found. Routine biochemistry tests may reveal panhypoproteinemia in animals with diffuse lymphoma, although B cell AL may occasionally cause hyperglobulinemia by a monoclonal gammopathy. Alterations in serum folate or cobalamin concentrations may be the result of malabsorption, SIBO secondary to intestinal obstruction, or consumption of folic acid by tumor cells.

Answer 299

Dogs with diffuse alimentary AL usually respond poorly to therapy, and there is a risk of intestinal perforation. This is in contrast to multicentric lymphoma and even to dogs with lymphoma restricted to the rectum. In contrast, the prognosis in cats is more favorable; some attain prolonged remission. Cell lineage appears to be important in response to treatment and prognosis. In cats the low-grade small-cell form has a much better prognosis than intermediate- and high-grade lymphomas. Good responses to combination chemotherapy have been reported, either with standard, multidrug protocols or with an “oral only” regimen (e.g., prednisolone and chlorambucil), especially in feline low-grade lymphoma. The latter treatment is well tolerated and may be particularly applicable to cases in which the differentiation between AL and LPE is uncertain, as the treatment is also applicable in severe IBD. A large-cell, lymphoblastic form tends to be more aggressive and resistant to treatment.

Answer 300

Both adenoma and adenocarcinoma are more common in the canine LI than in the SI; the converse is true in cats. In the dog SI, carcinoma has a predilection for the duodenum, whereas the jejunum and ileum are more commonly affected in cats. Adenocarcinomas are locally infiltrative and may extend to the serosa and mesentery and metastasize to local lymph nodes and/or the peritoneal cavity.

Answer 301

Smooth-muscle tumors of the SI, leiomyoma and leiomyosarcoma, are uncommon in dogs (average age 10 years) but rare in cats. Paraneoplastic effects are reported, especially hypoglycemia as a result of production of an insulin-like growth factor II-like peptide. Other paraneoplastic syndromes associated with leiomyosarcomas include nephrogenic diabetes insipidus and erythrocytosis. Findings such as polycythemia or hypoglycemia may reflect the consequences of direct or paraneoplastic effects, but tests may be unremarkable. Iron-deficiency anemia may develop without any overt GI signs.

Answer 302

Adynamic ileus is a common sequela to parvoviral enteritis, abdominal surgery, pancreatitis, peritonitis, endotoxemia, hypokalemia, and dysautonomia. Dysautonomia often shows multiorgan involvement.

Answer 303

A condition in which patients show clinical evidence consistent with an obstruction, but no mechanical cause can be found. The condition has been associated with both visceral neuropathies and myopathies in humans, and such causes may be seen in small animals. Most canine cases are associated with idiopathic sclerosing enteropathy, with fibrosis and a mononuclear cell infiltrate of the tunica muscularis. Feline intestinal pseudoobstruction may be primary or secondary to intestinal lymphoma.

Answer 304

The 5-HT4 receptor agonist cisapride, the D2 dopaminergic antagonist metoclopramide, and motilin-like drugs such as erythromycin. In dogs and cats, cisapride appears to be the most effective agent, but it is no longer available in many countries because of human toxicity. Antibacterials may also be appropriate, given the probability of secondary SIBO. Unfortunately, most cases reported in the veterinary literature responded poorly to therapy, and the prognosis is grave.

Answer 305

Extraluminal, intramural, or intraluminal mass lesions. Most intraluminal obstructions are caused by foreign objects. Intramural causes include intestinal neoplasias, hematomas, granulomas (e.g., focal FIP, phycomycosis), IBD, and stricture, such as after foreign body impaction or surgery.

Answer 306

Ileocolic intussusception is the most common anatomical variant, and in severe cases, the intussuscipiens may migrate out through the anus. Younger animals are more likely to develop intussusceptions, especially after a case of gastroenteritis or after intestinal surgery. Neoplasia is the more frequent cause in middle-aged and older animals, with the mass acting as a nidus for the infolding of the SI.

Answer 307

The situation that occurs when more than two thirds of the SI are absent because of resection or, rarely, due to a congenital anomaly. Clinical signs such as diarrhea are a result of insufficient functional mass of SI for assimilation of nutrients and electrolytes. The degree of malabsorption depends on the length of intestine resected. The site of resection is also important; removal of the ileocolic valve predisposes to ascending bacterial colonization. Massive resection also precipitates changes in GI hormones, leading to hypergastrinemia and increased acid secretion. Parenteral cobalamin supplementation is essential if the ileum has been resected. H2-receptor antagonists may be used in the postoperative period to counteract possible hypergastrinemia. Antimicrobial agents may be necessary if the ileocecocolic junction has been resected or if secondary SIBO is suspected. If the response to diet and antibiotics is poor, antisecretory agents (loperamide, diphenoxylate, or octreotide) may be required. Bile salt–binding resin such as cholestyramine may help reduce colonic secretion caused by bile salts malabsorbed after ileal resection.

Answer 308

Recurrent, usually acute episodes of abdominal pain, borborygmi, and diarrhea. In the absence of morphologic changes, a functional disorder is considered the cause of this enigmatic problem. Disordered intestinal motility may be of primary importance

Answer 309

A variety of treatments, including antispasmodics—anticholinergics and also smooth-muscle relaxants, such as mebeverine—anxiolytics such as diazepam and chlordiazepoxide, and dietary modification (low fat, increased fiber) have been tried with no consistent results. condition to diagnose and treat successfully until its etiology is better understood.

Answer 310

The cecum, colon, rectum, and anal canal.

Answer 311

Ileocolic junction

Answer 312

The ascending, transverse, and descending segments. In dogs and cats, the large intestine contributes 20% to 25% of the total (small and large) intestinal length

Answer 313

Blood supply to the colon is provided through the cranial and caudal mesenteric arteries. The veins of the colon all terminate in the portal vein. The lymph from the colon is collected to the right, middle, and left colic lymph nodes. Parasympathetic innervation to the proximal colon arises from the vagus nerve and to the distal colon from the pelvic nerves. Sympathetic innervation stems from the paravertebral ganglia and follows the lumbar splanchnic nerves and mesenteric arteries to the colonic mucosa and muscularis. The intestines also contain an intramural nervous system, which is located in the tela subserosa, between the two layers of the muscularis, and in the tela submucosa. They are responsible for the autonomous nervous functions of the intestine

Answer 314

The mucosa, submucosa, muscularis, and serosa.

Answer 315

The large intestine contains no villi, less microvilli, and more mucus-producing goblet cells. Also numerous straight, tubular crypts, called crypts of Lieberkühn, are present in the colon.

Answer 316

Numerous straight, tubular crypts, called crypts of Lieberkühn, are present in the colon, extending through the entire thickness of the mucosa. These crypts contain epithelial, mucus-producing, and endocrine cells. Cells at the base of crypts proliferate and migrate to the top of the epithelium, where they differentiate into epithelial cells, mucus-secreting goblet cells, and endocrine cells.

Answer 317

The cell turnover in the colon is slower than in the small intestine and requires 4 to 7 days. Among the products of the endocrine cells are polypeptide P, somatostatin, and glucagon-like peptides.

Answer 318

Intraepithelial lymphocytes consist predominantly of the CD8 T cell subtype. At the crypt, epithelial cells in the colon have a high mitotic index and migrate quickly up to replace surface epithelial cells

Answer 319

Lymphocytes, plasma cells, mast cells, macrophages, eosinophils, enteric neurons, fibroblasts.

Answer 320

The muscularis is composed of inner circular and outer longitudinal muscle layers. 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. The serosa is composed of mesothelial cells and covers only the portions of the large bowel found within the peritoneal cavity (cecum and colon).

Answer 321

-The extraction of water and electrolytes from the proximal colon, -Storage of feces, -The process of defecation in the distal colon and rectum. -Microbial fermentation of undigested ingesta also occurs in the colon. -The interaction of the microflora with the cells of the mucosal immune system seems to be an important part of the immune system.

Answer 322

The colon has a large capacity to absorb water, and in the healthy large intestine, 90% of fecal water is absorbed. The absorption of water occurs passively across an osmotic gradient by coabsorption of sodium. In the inflammatory state, the colon has a reduced capacity to absorb water, which leads to diarrhea, the hallmark of large intestinal disease (see Diagnostic Evaluation).

Answer 323

Sodium absorption occurs mainly in the proximal colon. Neutrality is maintained by the exchange of sodium and potassium against chloride and bicarbonate. Potassium is absorbed via a K+/H+ exchange transporter, and its secretion occurs via active conductance in the distal colon.

Answer 324

Absorption of sodium and secretion of potassium into the colonic lumen is also stimulated by aldosterone and glucocorticoids. These hormones affect colonic transport by enhancing the activity of the Na+/K+-ATPase pump. Bicarbonate is also important to neutralize acids produced by bacteria in the colonic lumen.

Answer 325

Mucus production has important physiological functions in the colon. It acts as a lubricant, and thereby not only facilitates defecation, it also protects the mucosa from damage. Pathogenic microorganisms and enterotoxins can be bound by mucus before they reach the epithelium.

Answer 326

When the large intestine is inflamed, large amounts of mucus, water, and electrolytes can be secreted, resulting in colitis. Genes responsible for the expression of mucus proteins, such as mucin-2, could be a component of autoimmune inflammatory disorders, including inflammtory bowel disease.[11]

Answer 327

Absorption of water and electrolytes from the feces & Control of defecation The enteric nervous system is crucial to the local control. If absent, individuals cannot survive without colectomy.

Answer 328

Reflex pathways control colonic wall movement, water and electrolyte secretion, and local blood flow. The sympathetic nervous system acts primarily to restrict progression of contents towards the rectum by inhibiting the activity of the enteric neurons that control activity and by relaxing the nonsphincter muscles and contracting the sphincters. Sympathetic activation also suppresses the secretion of water and electrolytes in the colonic lumen.[

Answer 329

There are regional differences in colonic motility patterns. In the proximal colon, mixing of content and absorption of water are the primary goals, achieved through distally propagating contractions, called rhythmic phasic contractions (RPCs), as well as retrograde contractions, called retrograde giant contractions (RGCs).[15],[16] In the distal colon, migrating spike bursts and RGCs propel the feces towards the rectum and help to expel them. In addition, tonic contractions lasting from several minutes to hours are present in both the proximal and the distal colon.

Answer 330

Essential functions affecting the mucosal immune system, energy metabolism of the epithelial cells, complex macromolecule absorption, and synthesis of amino acids and vitamins.

Answer 331

Bacterial colonization of the gut begins shortly after birth. From that point, the microflora changes until the gastrointestinal (GI) immune system has properly developed. After that, the composition of the microflora seems to be stable in healthy individuals, although its composition can undergo minor changes again in old age. Some degree of innate immune recognition of commensal bacteria is essential for normal development and function of the mucosa, which explains why mice reared under germ-free conditions exhibit numerous immunologic defects

Answer 332

It has recently become evident that most bacteria in the GI tract, and especially in the colon, are noncultivable; and it has been estimated that up to 70% of the microflora could represent unknown species. The bacterial diversity increases gradually along the intestinal tract from the duodenum to the colon in healthy hound dogs. Fusobacteriales were most abundant in the colon (33% of all identified clones), followed by Bacteroidales (30%) and Clostridiales of the cluster XIVa (26%).[28]

Answer 333

Into acetate, proprionate, butyrate, hydrogen, methane, and carbon dioxide.

Answer 334

The gut-associated lymphoid tissue (GALT) consists of inductive sites—including isolated lymphoid follicles in the colon (the equivalent of IPeyer's patches in the small intestine) and the mesenteric lymph nodes—and the effector site, comprised of the LP mucosae.

Answer 335

So-called microfold (M) cells are particularly abundant in the epithelium overlying the lymphoid follicles in the colon. The LP beneath these M cells is rich in T cells, B cells, and dendritic cells (DCs).

Answer 336

Role of continuously sampling antigens from the lumen by extending dendrites between the epithelial cells. They then activate various different immune cells of the adaptive immune system (T cells and B cells) in the LP for an inflammatory or antiinflammatory response (i.e., oral tolerance), depending on the nature of the antigen sampled.

Answer 337

B cells develop under the influence of transforming growth factor-β and IL-10 from DCs and T cells and undergo a class switch to an IgA-producing phenotype. These B cells then migrate to the mesenteric lymph nodes, circulate through the lymphatic system of the body, and migrate back to the LP, driven by adhesion molecules homing them to high endothelial venules in the LP.

Answer 338

Mast cells are also found abundantly in the LP, and they play an important role in the host immune response to parasites and also to certain bacteria. Eosinophils also belong to the normal resident cell population in the LP, and they are particularly important in the immune response to parasites and in allergic reactions. T cells in the LP are mainly of the CD4+ and CD8+ cell subtype. IELs seem to play an important role in maintaining normal immune homeostasis in the gut and also in cancer surveillance.

Answer 339

Intestinal epithelial cells also play an important part in the intestinal mucosal immune system. They can act as nonprofessional antigen-presenting cells by continuously sampling antigens from the intestinal lumen and presenting them to LP cells through expression of major histocompatibility complex (MHC) II. They recognize and respond to bacterial and viral microbe-associated molecular patterns (MAMPs) by virtue of pattern-recognition receptors (PRRs). The epithelial cells can then produce cytokines that will influence immune responses in the LP.

Answer 340

The innate immune system—comprised mainly of epithelial cells, macrophages, and DCs—appears to determine the ensuing immune response. In the healthy gut, innate immune cells recognize commensals and elicit basal or tonic signals in the absence of full activation of the immune system, and oral tolerance ensues.[37] Toll-like receptors (TLRs) and nuclear organization domain (NOD) receptors are PRRs of the innate immune system located on the surface or in the cytoplasm of epithelial cells and DCs.

Answer 341

The TLRs and NOD receptors recognize specific MAMP molecules, which are conserved molecules found on bacteria and other infectious agents. Different TLRs recognize different MAMPs: for example, TLR4 recognizes lipopolysaccharide (LPS) present in the cell wall of gram-negative bacteria; TLR2 recognizes lipopeptides and lipoteichoic acid, mainly found in the cell wall of gram-positive bacteria; and TLR5 recognizes flagellin, the main protein of bacterial flagella.

Answer 342

Binding of MAMPs by TLRs initiates a complex intracellular signaling pathway, culminating in the activation of transcription factor NF-κB.[40] This results in the transcription and secretion of a variety of proinflammatory and antiinflammatory cytokines and chemokines from the cell bearing the TLR. If successful, immune cells activated by this response clear offending pathogens or remain unresponsive towards commensal organisms present in the intestinal lumen.

Answer 343

How do epithelial cells and DCs differentiate between harmless commensals and pathogens? First, some pathogens have virulence factors that enable them to invade epithelia, such as Salmonella, Shigella, and Listeria. These bacteria only trigger inflammatory responses in the LP when they have trespassed the epithelia. The selective distribution of some TLRs on the surface of cells might help distinguish pathogens and commensals in such cases. For example, TLR5, which recognizes bacterial flagellin on Salmonella and other flagellated bacteria, is located on the basolateral side of the intestinal epithelial cells, where it can only be activated by invasive bacteria. Other PRRs are located intracellularly, such as NOD2, TLR9, TLR3 and TLR7. The MAMP motifs these receptors recognize will only activate a response once they have invaded the cytoplasm of the cells. However, this does not fully explain why commensals will not elicit an inflammatory response in the LP, as intestinal epithelial cells also constantly recognize commensals by binding to TLRs.

Answer 344

Studies suggest that some commensal bacteria can actively modulate the intracellular signaling after binding to their respective TLR. This has been shown to be the case for lactobacilli, Bacteroides, nonpathogenic Escherichia coli, and attenuated Salmonella that lack flagellin

Answer 345

DCs in the LP are also believed to play a major role in development of an adaptive immune response, involving T cells and B cells, in inflammatory processes.

Answer 346

T cells play a major role in inflammation as effector cells in the adaptive arm of the immune system, as they secrete cytokines that recruit appropriate inflammatory cells. Several major CD4+ effector-cell subsets exist in the intestinal mucosa: Th1, Th2, T-regulatory, and Th17 cells. DCs encountering commensals or pathogens through PRRs will produce either IL-23 preferentially or IL-12 and IL-27 predominantly. It seems that this decision drives T cells to differentiate from naive T cells into either Th1 or Th17 cells, which produce proinflammatory cytokines

Answer 347

In the presence of commensals, and in normal intestinal homeostasis, a balance between effector and regulatory subpopulations of T cells is maintained through this tightly controlled cytokine network, such that the effects of Th17 cells are counterregulated by cytokines produced by T-regulatory cells and Th3 cells.

Answer 348

Table • 271-2 -- Clinical Signs Associated with Diarrhea: Large Bowel versus Small Bowel

Answer 349

Constipation is the second most common sign in patients presenting with underlying colonic disease. Constipation refers to reduced or absent defecation for several days to weeks. Sequelae can be dehydration, weight loss, adbominal pain, and mild to moderate mesenteric lymphadenopathy. Special emphasis should be placed on findings such as abdominal masses (neoplasia), abdominal pain (foreign bodies, colonic perforation), autonomic neuropathy (dysautonomia), hind-limb paresis (lumbar spinal cord lesions), pelvic fractures, and perineal hernias

Answer 350

Anemia due to chronic disease (mostly mild to moderate and nonregenerative) Anemia due to GI blood loss (mild to severe, regenerative to nonregenerative) Leukocytosis (seen in IBD, neoplasia, and infection) Eosinophilia (seen in parasitosis, Addison's disease, mast cell tumors, and hypereosinophilic syndrome) Decreased total protein concentrations (concurrent protein-losing enteropathy) Increased globulin concentration (FIP, IBD, infections, neoplasia) Increased serum calcium concentrations (neoplasia, fungal granulomas) Hypoglycemia (large abdominal tumors, leiomyosarcomas) Decreased sodium concentration concurrent with increased potassium concentration (Addison's disease, pseudo-Addison's disease).

Answer 351

If there is evidence of small intestine disease, serum cobalamin and folate concentrations should be obtained. Folate is mainly absorbed in the proximal small intestine; if concentrations are low, it indicates proximal small intestine disease. Cobalamin is absorbed in the terminal ileum, and low serum concentrations indicate disease affecting the ileum. Measuring cobalamin levels and supplementing vitamin B12 in cases with deficiencies therefore seems to be just as important in dogs as in cats with signs of chronic small intestine diarrhea.

Answer 352

Excluding exocrine pancreatic insufficiency by performing a serum trypsinlike immunoreactivity measurement, and investigating the possibility of pancreatitis by measuring serum canine pancreatic lipase and/or performing abdominal ultrasound, could be indicated, depending on the clinical signs pertaining to small intestine disease.

Answer 353

Campylobacter spp., Clostridium perfringens and Clostridium difficile, Salmonella spp., and possibly Yersinia spp. However, it has been demonstrated that organisms such as Campylobacter spp. can be found in healthy dogs as well as in dogs with diarrhea. This emphasizes that a positive test must be interpreted in light of other clinical findings, and sometimes trial therapy will more effectively diagnose such diseases. Quantitative culture of bacteria, protozoa, and fungi in the colon is no longer recommended, as the number of culturable bacterial species living in the colon is estimated to encompass only about 30% of the total microbiome.

Answer 354

Polymerase chain reaction (PCR)–based tests have become available for several infectious agents, such as tritrichomonas foetus, Pythium spp., Campylobacter jejuni, C. perfringens and C. difficile, Salmonella spp., and Brachyspira spp.

Answer 355

On biochemistry profile, some dogs may show evidence of increased serum potassium concentrations along with decreased sodium concentrations, which has been described as “pseudoaddisonian,” as the dogs have a normal response to adrenocorticotropic hormone stimulation.

Answer 356

Heterobilharzia americana causes schistosomiasis in dogs in the Gulf Coast area of the United States. The life cycle of H. americana involves at least one intermediate host, mostly snails. The cercariae from the snail penetrate the skin of dogs and migrate to the liver. The parasites mature in the liver and lay eggs in the terminal mesenteric venules. They then migrate through the bowel wall by causing severe granulomatous inflammation at the site of penetration.

Answer 357

Tritrichomonas foetus is a flagellate similar in size and shape to Giardia, but it only exists in the trophozoite form. T. foetus is an important pathogen in cattle, where it causes infertility and abortion. Transmission occurs directly via the orofecal route, with a few reports of infections in cats causing feline trichomonal diarrhea. (The prevalence in healthy cats can be up to 31%).

Answer 358

Giardiasis is mostly a disease of the small intestine, but in cats, Giardia can also colonize the colon. Cysts are the infective form, are shed intermittently, and can survive several months in wet, cold conditions. Transmission occurs via the orofecal route, and the trophozoites live in the intestinal lumen after shedding from the cysts.

Answer 359

Histoplasma capsulatum causes chronic large-intestinal diarrhea in young dogs and cats in endemic temperate and subtropical regions of the world.

Answer 360

Pythium insidiosum, an aquatic pathogen belonging to the class of Oomycetes, causes pythiosis. Large-breed male dogs, especially Labradors, seem to be affected most commonly, as the organism lives in warm, freshwater reservoirs. There is a predilection for infection of the skin and/or the GI tract. Endemic areas are the Gulf Coast region of the United States, but the disease has been diagnosed as far north as Virginia and as far west as California. If the GI tract is affected, upper GI obstruction is seen most commonly from severe infiltration of the gastric wall. Sometimes, the colon is affected as well, resulting in large-intestinal diarrhea.

Answer 361

Bacteria Campylobacter are gram-negative, motile, spiral-shaped bacteria that grow in culture under microaerophilic conditions. Campylobacter jejuni, Campylobacter upsaliensis, Campylobacter coli, and Campylobacter helveticus have been detected in feces of healthy and diarrheic dogs and cats. Campylobacter organisms attach to the intestinal epithelial cells and can cause superficial erosive enterocolitis. Clinical signs may depend on the number of bacteria infecting an animal and vary widely, from mild diarrhea to bloody diarrhea with severe dehydration. On direct fecal examination, large numbers of curved, motile bacteria can sometimes be detected. However, culture of fresh fecal samples or PCR are required for definitive diagnosis.

Answer 362

C. perfringens producing type A toxins have been associated with enterocolitis in dogs. Type A toxins consist of major toxin A and enterotoxin, also called Clostridium perfringens enterotoxin (CPE), which causes food poisoning in humans. CPE has been associated with acute hemorrhagic colitis in dogs, especially in kennels and under boarding conditions. However, healthy dogs can also harbor C. perfringens and CPE, therefore it can only be classified as a suspected pathogen in dogs, as Koch's postulates are not met. Culture of C. perfringens from feces is not sufficient to diagnose the infection. Immunoassays or PCR are available to detect CPE in feces, however, quantification of the enterotoxin is not possible. The clinical value of these tests is therefore questionable, as CPE is detected with similar frequency in feces from healthy dogs. C. perfringens is susceptible to metronidazole. The prognosis is good, and supportive treatment alone is sometimes just as successful as antibiotic treatment.

Answer 363

C. difficile produces two major toxins, A and B. These toxins cause pseudomembranous colitis in humans. The organism can be cultured from feces of healthy and diarrheic dogs, however, toxins are more frequently found in dogs with diarrhea.

Answer 364

A defective mucosal barrier can contribute to a massive influx of microbes and food antigens into the LP, where they trigger proinflammatory cytokine release by T cells. Defects in the recognition of microbes by the innate immune system leads to misrepresentation of such microbes as pathogens instead of commensals to T cells in the LP, again triggering proinflammatory responses. Finally, aberrant adaptive immune responses will contribute to the production of proinflammatory cytokines, all leading to inflammatory histopathology. Even though there are obvious clinical and histologic differences between human IBD and the disease encountered in dogs and cats, many of the abnormalities of the innate and adaptive immune systems in the mucosa are being unraveled in small animals. There is evidence that the molecular pathogenesis of the two diseases is similar.

Answer 365

Each TLR recognizes specific common patterns on microbes, such as LPS (TLR4), flagellin (TLR5), or viral nucleic acids (TLR7 and TLR8; see Table 271-1).

Answer 366

Maintaining hyporesponsiveness to innocuous luminal commensals, Inhibition of allergic responses to food allergens, Protection of the mucosal barrier function. This means that in the case of a commensal or common food antigen being recognized by TLRs, naïve T cells will preferentially develop into T-regulatory cells, which downregulate inflammatory responses. However, if a pathogen is encountered by PRRs, the signal to naïve T cells will contain specific information to drive the adaptive immune response to be able to eradicate the pathogen. For instance, in the case of a parasite being encountered by PRRs, the appropriate adaptive immune response will be characterized by differentiation of naïve T cells into predominantly Th2 cells, which secrete cytokines that attract eosinophils, basophils, and mast cells to kill and eliminate the parasites. In the case of viruses being encountered, the adaptive immune response will be characterized by the development of Th1 cells, which secrete cytokines that attract macrophages to eliminate the pathogen. However, in the case of a dysfunctional PRR being displayed on the surface of intestinal epithelial cells or DCs, the signal reaching naïve T cells may be incorrect, therefore sending a “danger” signal when encountering a commensal or common food antigen. This leads to the aberrant differentiation of naïve T cells into Th17 cells, which produce proinflammatory cytokines such as IL-17, IL-22, and tumor necrosis factor. These cytokines have recently been shown to be the signature cytokines driving the inflammation in humans with Crohn's disease. Further evidence that disturbances of the innate immunity play a role in the pathogenesis of IBD is provided by understanding that several PRRs are upregulated in the inflamed mucosa of patients with IBD, and the degree of overexpression correlates with clinical disease activity in people.

Answer 367

Expectedly, NODs and TLRs are also a focus of attention in dogs with chronic enteropathies. Studies indicate that cultured primary canine colonocytes can express NOD2, TLR2, and TLR4 when stimulated by appropriate ligands. In a study looking at TLR2 and TLR4 expression profiles in German Shepherds with severe IBD, where high levels of these receptors were found in the duodenum. Only limited data are available regarding PRR expression profiles in the colons of dogs with IBD, so the latter findings need to be interpreted with caution for the large intestine, until more results become available. Both T lymphocytes and B lymphocytes, as well as IgG-positive plasma cells, appear to be increased in the inflamed colonic mucosa of dogs with IBD. Results conflict regarding the nature of the specific cytokine pattern seen in dogs with IBD. No published data exist regarding cytokine expression in cats with 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. Cytokines of the just recently discovered IL-17 type have not been evaluated in dogs and cats but may well be the dominant cytokine response in IBD in these species as well. It has been shown that various dietary components can exert deleterious or beneficial effects on intestinal microflora and mucosa. It is therefore plausible that dietary changes could influence the mucosal inflammatory process.

Answer 368

Adverse reactions to food can result from immunologic (food allergy) and nonimmunologic (food intolerance) mechanisms. In dogs and cats, the clinical differentiation between food allergy and food intolerance relies heavily on restricted antigen dietary trials

Answer 369

All dogs and cats with GI manifestation of adverse reactions to food improve when fed a novel diet, especially if it is designed to avoid antigens found in their original diet. When challenged with their original food, they relapse. However, only food-allergic dogs and cats also relapse when their low-allergen diet is added to proteins from a single source, such as beef, chicken, milk, or any protein that was part of their original diet.

Answer 370

It may decrease the total absorptive capacity of the mucosa through disappearance of functional colonocytes, increased epithelial permeability, and disturbance of sodium and chloride transport. Additionally, colitis has direct effects on colonic motility. Decreased nonpropulsive motility may be explained by disturbances of the circular colonic smooth-muscle cells, which is associated with inflammation. Inflammation may impair calcium mobilization, change the expression of key signaling molecules for excitation-contraction coupling, inhibit muscarinic signaling, and increase transcription of nuclear factor kappa B (NF-κB). Finally, absorptive and motility disorders may change the composition of the luminal commensal flora that play an important role in the maintenance of colonic function. Changing flora may contribute to further deterioration.

Answer 371

CBC, blood chemistry, and urinalysis results are not usually significantly abnormal in dogs and cats with large-intestinal IBD. This may be different in animals with generalized GI inflammation that includes the small intestine, where leukocytosis with neutrophilia and left shift, hypoproteinemia with hypoalbuminemia and hypoglobulinemia, and sometimes mildly to moderately increased liver enzyme activities can be present

Answer 372

Fermentable fibers are metabolized to short-chain fatty acids by large-intestinal flora and provide a useful source of energy. Overall, they enhance the structure and function of the intestinal epithelium. Examples of fermentable fibers include beet pulp, psyllium, and fructooligosaccharides (FOSs), which are oligosaccharides that resist digestion in the small intestine and are fermented by colonic bacterial flora.

Answer 373

Proliferation of colonocytes by increasing blood flow to the colonic mucosa & Promotion of epithelial cell differentiation into fully functional colonocytes. Additionally, FOSs are prebiotics and are therefore able to influence the composition of the large bowel commensal flora. In cats, they were reported to increase colonic fecal concentrations of Bacteroides and Lactobacillum spp. and to decrease those of E. coli and C. perfringens Dietary fiber also has a beneficial effect on colonic motility.

Answer 374

nutrient digestibility.

Answer 375

It has great water-holding capacity and forms gels in water, two properties that can contribute to improvement of fecal consistency.

Answer 376

Live microorganisms that may be beneficial to the host GI tract

Answer 377

Besides its antimicrobial effects against a variety of obligate anaerobic bacteria, metronidazole is also effective against Giardia spp. Furthermore, metronidazole has been shown to have immunomodulatory effects, and it affects various steps in innate and adaptive sequences of the immune response. It is used in dogs and cats with colitis to modify the intestinal flora, decreasing obligate anaerobes and inflammation.

Answer 378

If a suspension is administered to a cat, metronidazole hydrochloride is not a palatable formulation and may elicit ptyalism and anorexia. Metronidazole benzoate is the preferable formulation for cats, but it contains only 62% metronidazole and therefore requires a dose adjustment. Other side effects of metronidazole are rare and include vomiting and diarrhea, although cats may be more susceptible due to probable increased half-life of the drug. Hepatotoxicity and neurotoxicity have been reported at higher dosages.

Answer 379

Sulfasalazine consists of a nonsteroidal antiinflammatory drug molecule (salicylic acid or mesalamine) linked by an azo bond to a sulfonamide (sulfapyridine). Most 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 have therapeutic effect. It is absorbed, metabolized in the liver, and filtered through the kidneys. Mesalamine unfolds its antiinflammatory effects on the colonic mucosa by inhibiting prostaglandin and leukotriene synthesis.

Answer 380

Keratoconjunctivitis sicca (KCS). Although the exact mechanism of action is unknown, sulfasalazine may be responsible for the damage to lacrimal glands. Vomiting may occur as well but can be prevented if the drug is administered with food.

Answer 381

Corticosteroids' desired antiinflammatory effects are due to the inhibition of phospholipase A, which extracts arachidonic acid from the cell membrane phospholipids, therefore inhibiting the cascade leading to proinflammatory prostaglandin and leukotriene synthesis. Moreover, when administered at high doses, corticosteroids effectively inhibit innate and acquired immunity. Chlorambucil has been used in place of azathioprine in some difficult or refractory cats with IBD.

Answer 382

In animals refractory to immune-suppressive doses of corticosteroids, additional immune-suppressive drugs, such as azathioprine (dogs only) and cyclosporine A, may be helpful. Azathioprine is a purine analog that, after DNA incorporation, inhibits lymphocyte activation and proliferation. It is rarely effective as a single agent and should instead be used as adjunctive therapy with glucocorticoids. Azathioprine may have a significant steroid-sparing effect in canine IBD. It may take several weeks or months of therapy for azathioprine to become maximally effective. Cats particularly should be monitored for side effects, including myelosuppression, hepatic disease, and acute pancreatic necrosis.

Answer 383

Cyclosporine A reduces IL-2 production in T cells and therefore renders them more susceptible to apoptosis. Improvement in IBD dogs may be due to diminished T cell numbers in the mucosa after treatment, potentially reducing relapse episodes for longer periods of time. Side effects of cyclosporine were vomiting 1 to 2 hours after giving the capsules, alopecia, and gingival hyperplasia.ar.

Answer 384

HUC also occurs infrequently in other breeds, such as Mastiffs, Alaskan Malamutes, French Bulldogs, and English Bulldogs. Also in one cat.

Answer 385

The role played by PAS-positive macrophages is intriguing, as PAS stains intracellular phagocytosed material in the macrophages, and early electron-microscopic studies have demonstrated so-called residual bodies that resemble bacteria-like organisms in granules of PAS-positive staining macrophages.

Answer 386

. Electron microscopy of HUC lesions allowed identification and localization of bacteria to the intracellular compartment of PAS-positive macrophages.Additionally, the intracellular material found in PAS-positive macrophages from dogs with HUC stains positive for polyclonal antibodies against E. coli The E. coli strains associated with HUC have a similar phenotype with the adhesive and invasive behavior displayed by E. coli isolates that were recently associated with Crohn's disease in people; which resembles canine HUC in its histologic appearance, as granulomas are the main feature of the disease

Answer 387

.People with Crohn's disease have polymorphisms in certain PRRs, such as NOD2, which result in a disturbed response of human monocytes to E. coli LF82, linking a genetic defect in innate immunity with functional disease for the first time. It is possible that similar defects in PRRs, as have been seen in people with IBD, could be present in Boxers with HUC. Genetic predisposition for HUC is likely to play a role. 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 the innate immunity renders dogs with HUC susceptible to infection with specific bacteria, such as strains of adhesive and invasive E. coli.

Answer 388

HUC: The onset of disease is usually before 2 years of age. Clinical signs are those of severe, chronic, large-intestinal inflammation and include diarrhea, hematochezia, increased frequency of defecation, tenesmus, and presence of excessive mucus in the feces. Physical examination findings are normal in many dogs with HUC, however, weight loss and inappetence may be seen in severe cases, and should prompt more invasive investigations. Fresh blood and mucus can be seen upon rectal examination.

Answer 389

Accumulation of large macrophages that stain strongly positive in their cytoplasm with PAS is pathognomonic for HUC and remains the best way to confirm the diagnosis.

Answer 390

Enrofloxacin or a combination protocol with enrofloxacin, amoxicillin, and metronidazole. 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 therapy. Some needs treatment for life.

Answer 391

Adenocarcinomas, lymphosarcomas, and GI stromal tumors (leiomyosarcoma, neurofibrosarcoma, fibrosarcoma, and ganglioneuroma). Most colonic neoplasia develops in the descending colon and rectum, although leiomyosarcomas more frequently develop in the cecum. Local tumor invasion apparently occurs at a slower rate with canine colonic neoplasia, and metastasis to distant sites is relatively uncommon. Benign colonic neoplasia such as adenomas, adenomatous polyps, and leiomyomas are much less common than malignant tumors. Malignant transformation of adenomatous polyps to carcinoma in situ and invasive adenocarcinoma has been demonstrated in dogs. All of the aforementioned tumors are associated with signs of inflammation and obstruction, such as hematochezia, tenesmus, and dyschezia.

Answer 392

In cats, adenocarcinoma is the most common tumor of the large intestine, followed by lymphosarcoma and mast cell tumors. The most common sites of colonic neoplasia in cats are the descending colon and the ileocolic sphincter. Unlike dogs, cats with colonic tumors have a high rate of local metastasis, which is associated with decreased survival time.

Answer 393

Mechanical obstruction is the most common pathophysiologic consequence of locally invasive colonic tumors. Other nonneoplastic processes such as intussusception, FIP granuloma, fibrosing stricture, linear and nonlinear foreign bodies, hematoma, and phycomycosis lesions also cause intraluminal obstruction. 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

Answer 394

Most cats with colonic and alimentary lymphosarcoma are FeLV-negative. Although most lymphomas appear to be comprised of malignant T lymphocytes, most colonic and alimentary lymphomas in cats are of B cell origin.

Answer 395

Intussusception DEFINITION AND BACKGROUND Intussusception is an invagination of one segment of the GI 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. 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; ileocolic; and ileocecal. Of the three forms of enterocolic intussusception, the ileocolic intussusception is the one most frequently encountered in practice.

Answer 396

Intestinal parasitism, viral enteritis, foreign bodies, and masses, but in dogs and cats, most intussusceptions are idiopathic.

Answer 397

PATHOPHYSIOLOGY: 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 distension of the bowel segment proximal to the intussusception. The degree of distension 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.

Answer 398

CAUSE: The etiopathogenesis of idiopathic megacolon is incompletely understood. Several reviews have emphasized the importance of considering an extensive list of differential diagnoses, such as neuromuscular, mechanical, inflammatory, metabolic and endocrine, pharmacologic, environmental, and behavioral causes for the obstipated cat. A review of published cases suggests that 62% of cases of obstipation are accounted for by idiopathic megacolon.

Answer 399

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%). A smaller number of cases are accounted for by complications of colopexy (1%) and colonic neoplasia (1%); colonic hypoganglionosis or aganglionosis was suspected, but not proved, in another 2% of cases. Endocrine factors (e.g., obesity, hypothyroidism) were cited in several cases but were not necessarily impugned as part of the pathogenesis of megacolon

Answer 400

PATHOPHYSIOLOGY 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 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.

Answer 401

infrequent or difficult evacuation of feces but does not necessarily imply a permanent loss of function.

Answer 402

Intractible constipation that has become refractory to cure or control is referred to as obstipation and therefore implies a permanent loss of function.

Answer 403

Megacolonic smooth muscle develops less isometric stress in response to neurotransmitters (acetylcholine, substance P, cholecystokinin), membrane depolarization (potassium chloride), or electrical field stimulation when compared with healthy controls

Answer 404

Urinary and fecal incontinence, regurgitation due to megaesophagus, mydriasis, decreased lacrimation, prolapse of the nictitating membrane, and bradycardia.

Answer 405

Although most cats with obstipation and megacolon are unlikely to have significant changes in laboratory data (e.g., CBC, serum chemistry, urinalysis), these tests should nonetheless be performed in all cats with constipation. Metabolic causes of constipation, such as dehydration, hypokalemia, and hypercalcemia may be detected in some. Basal serum T4 concentration and other thyroid function tests should also be considered in cats with recurrent constipation and other signs consistent with hypothyroidism.

Answer 406

Laxatives promote evacuation of the bowel through stimulation of fluid and electrolyte transport or increases in propulsive motility. Hundreds of products are available for the treatment of constipation. 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

Answer 407

A large body of anecdotal experience suggests that cisapride is effective in stimulating colonic propulsive motility in cats affected with mild to moderate idiopathic constipation;

Answer 408

A fiber-responsive large-bowel diarrheal syndrome similar to irritable bowel syndrome in humans has been characterized in dogs. Affected animals have a chronic idiopathic large-bowel–type diarrhea characterized by excessive fecal mucus, hematochezia, and tenesmus. Medical investigation is negative for bacterial and other pathogens, colitis, and colonic neoplasia, and the term chronic idiopathic large-bowel diarrhea is applied to the patient's disorder. Dogs affected with this syndrome may respond to the feeding of a highly digestible diet supplemented with soluble fiber

Answer 409

Neuromuscular dysfunction causes abnormal anorectal motility, fecal incontinence or constipation. Mucosal pathology usually results in inflammation and clinical signs such as hematochezia, tenesmus, pain, and frequent defecation. Pathology of the anorectum in the dog and cat is rarely associated with significant mortality (in the absence of neoplasia), but the resulting clinical signs can affect the quality of life of both pet and owner to the extent that some owners elect euthanasia.

Answer 410

The rectum, anal canal, internal and external anal sphincters, muscles of the pelvic diaphragm, and the perianal skin and subcutaneous tissues. The rectum is a continuation of the descending colon, extending from the pelvic inlet to the beginning of the anal canal.

Answer 411

Two muscle bundles, known as the internal and external anal sphincters, participate in defecation. The internal anal sphincter is essentially an enlargement of the circular smooth muscle of the rectum and functions involuntarily, whereas the external anal sphincter consists of striated muscle and is under voluntary control.

Answer 412

Anal glands, circumanal (hepatoid) glands, and glands of the anal sacs. Anal glands are modified tubuloalveolar sweat glands that secrete lipids of unknown function into the lumen of the anal canal. The circumanal glands are nonsecretory sebaceous glands, located subcutaneously around the anus. The glands of the anal sacs are located in the walls of the paired anal sacs, which are situated ventrolaterally and interposed between the inner smooth and outer striated muscle of the anal sphincters. Secretions from the anal sac glands accumulate within the anal sac and consist of desquamated epithelium, protein, sebaceous fluid, and bacteria.

Answer 413

Lymphatic drainage occurs via the internal iliac lymph nodes. The anorectum is innervated similarly to the colon, by a mysenteric and submucosal plexus containing sensory, integrative, and motor neurons (Figure 272-2). In addition to coordinating the storage and expulsion of feces, these neurons also regulate mucus secretion from goblet cells. The internal anal sphincter and rectum are innervated by autonomic fibers from the pelvic plexuses. Parasympathetic supply from the sacral spinal cord (S1-S3) via the pelvic nerve stimulates rectal motility while inhibiting, and thus relaxing, the internal anal sphincter. Sympathetic innervation arises from the lumbar spinal cord via the hypogastric nerves and is inhibitory to rectal motility and excitatory to the internal anal sphincter, causing contraction. The striated muscle of the external anal sphincter and the pelvic canal is innervated by the pudendal nerve. A functional external anal sphincter allows maximal distention for storage of fecal material while maintaining voluntary anal control. Relaxation of the internal and external anal sphincters, in conjunction with rectal contraction, permits defecation.

Answer 414

Because the anorectum has the same innervation as the bladder, the hypogastric nerves and the internal pudendal nerve, dysuria may also be associated with anorectal disease

Answer 415

The storage and evacuation of feces are controlled by reflex events in the rectum but can be modified by voluntary control of the external anal sphincter. The stimulus for defecation is increasing intraluminal pressure as the rectum distends with feces. Activation of stretch receptors initiates the rectoanal inhibition reflex, whereby the internal anal sphincter relaxes and the external anal sphincter contracts involuntarily. This reflex pathway consists of sensory perception (of changes in pressure, but not touch or pain) in the rectum, afferent transmission in the pelvic nerves, synapsing in the sacral spinal cord, and a motor response to rectal muscles.[5-8] When the more sensitive anal canal begins to distend, information is relayed via the sacral spinal cord to the cerebral cortex; rectoanal filling is then consciously perceived, and control is evoked to either facilitate or inhibit defecation. Voluntary contractions of the external anal sphincter and levator ani can suppress defecation if desired. The rectum adapts to a larger fecal volume by receptive relaxation, and sensory stimulation ceases.The process is repeated, and increasing fecal volumes stimulate a progressively stronger urge to defecate.

Answer 416

The act of defecation requires activation of parasympathetic efferents in the colon and rectum and somatic stimulation of the pelvic muscles and external anal sphincter. Contraction of the colonic smooth muscle propels feces from the distal colon to the rectum (a passive conduit), and the pelvic musculature and external sphincter relax. Intraabdominal pressure is increased by posturing, contraction of the diaphragm and abdominal muscles, and closing of the glottis, resulting in fecal expulsion.

Answer 417

Inflammation of the rectal mucosa. Localized proctitis can occur secondary to a rectal foreign body or rectal prolapse, but it is usually associated with colitis (colonic mucosal inflammation). Clinical signs of proctitis include tenesmus, dyschezia, and hematochezia. The presence of concurrent diarrhea suggests more diffuse inflammation involving the colonic mucosa.

Answer 418

A protrusion of the rectal wall and potentially other pelvic and abdominal organs (bladder and prostate gland, omentum, small intestine, descending colon) through a weakened portion of the pelvic diaphragm into the ischiorectal fossa.

Answer 419

Perianal fistula, also referred to as anal furunculosis, is a chronic, progressive, inflammatory disease of dogs, characterized by perianal ulceration and the formation of single or multiple ulcerated sinuses. In severe cases these lesions may affect the anus circumferentially and can cause severe pain, dyschezia, fecal incontinence, and rectal strictures. The etiology of the disease remains obscure. Perianal fistula is likely to have a complex etiology, whereby multiple genetic and environmental factors, such as dietary and microbial elements, interact to trigger and drive disease progression. Underlying immune dysfunction is also thought to contribute to disease pathogenesis, and it is interesting to note that the German Shepherd has been reported to suffer from impaired cell-mediated immunity and mucosal immunoglobulin A deficiency. Physical examination reveals single or multiple ulcerated, draining tracts and a foul-smelling mucoprurulent discharge

Answer 420

Anal sac tumors are relatively rare in dogs, however, they are almost invariably malignant adenocarcinomas. Adenocarcinomas are highly invasive tumors that can obliterate the anal sac, readily invade surrounding tissues, and frequently metastasize to regional lymph nodes and, less often, to the lungs and other internal organs; 36% to 96% have metastasized at presentation. Paraneoplastic hypercalcemia is reported in 25% to 51% of affected dogs. Anal sac masses are usually unilateral, they may be visible as a bulge in the perianal skin if sufficiently large, and they can be palpated in the rectum

Answer 421

In all dogs with anal sac masses, a minimum database (CBC, serum biochemistry, and urinalysis) should be established as part of disease staging. Three-view thoracic radiographs (thoracic metastasis usually appears nodular) and abdominal ultrasonography are also indicated. This highly aggressive tumor can also metastasize to bone, and it is advisable therefore to radiograph the caudal skeleton, particularly the lumbar vertebrae. Finding an anal sac mass in the presence of hypercalcemia and hypophosphatemia is highly suggestive of adenocarcinoma, however definitive diagnosis necessitates histopathologic examination of a tissue biopsy

Answer 422

Perianal adenomas are the most common perianal tumors in dogs, arising from the circumanal, or hepatoid cell, glands. These benign tumors are neither invasive nor metastatic and are not associated with paraneoplastic syndromes. Malignant perianal tumors are uncommon a

Answer 423

Fecal incontinence is the inability to retain feces, causing involuntary passage of fecal material. It can be classified according to pathophysiology as either reservoir or sphincter incontinence.

Answer 424

Reservoir incontinence is caused by colonic or rectal disease that causes decreased rectal capacity or compliance, for example, after subtotal colectomy, treatment of a rectal stricture, or fibrosis or mucosal thickening secondary to severe IBD. Sphincter incontinence develops when the external anal sphincter is denervated (neurogenic incontinence) or structurally damaged (nonneurogenic incontinence). Sphincter dysfunction generally results in more severe incontinence, because animals with reservoir incontinence are usually aware of the presence of feces in the rectum and are able to signal the need to defecate. They usually have frequent, voluntary defecation of small fecal balls rather than involuntary expulsion of feces. . The presence of concurrent urinary incontinence—and in male dogs, the inability to attain an erection—are suggestive of neurogenic incontinence.

Answer 425

The rectum, internal and external anal sphincters, coccygeus, and levator ani muscles are responsible for maintenance of continence, and these are innervated by the pelvic, hypogastric, pudendal, and sacral nerves. Lesions in any one of these structures may affect continence (Box 272-1). Occasionally, central nervous system disease has been associated with fecal incontinence. The most common causes of reservoir dysfunction are inflammatory, infectious, and neoplastic diseases of the colon, rectum, and anus. Concurrent urinary tract dysfunction can occur because of the common neural pathways.[3]

Gastrointestinal Disease Flashcards

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