Diseases of the Intestines

DIARRHEA

Diarrhea results from excessive fecal water content and is the most important clinical sign of intestinal disease in the dog and cat. It is characterized by an abnormal consistency and increase in frequency, fluidity, and volume of feces. The pathogenesis involves derangement of transmucosal water and solute fluxes caused by abnormal digestion, absorption, secretion, permeability, motility, or a combination of these.

Acute versus Chronic Diarrhea

For initial management of diarrhea, consider whether diarrhea is acute or chronic (based on history).

Acute Diarrhea

Acute diarrhea is characterized by sudden onset and short duration (3 weeks or less) of watery or watery-mucoid diarrhea. Diarrhea may be overtly bloody when associated with loss of mucosal integrity. Inappetence, lethargy, and vomiting are frequently associated signs; fever, abdominal pain, and significant dehydration suggest more serious intestinal disease.

• •Preliminary diagnostic considerations for diarrhea in the dog and cat should include diet (indiscretion, intolerance, hypersensitivity), medication side effects, toxicity, intestinal parasites (helminths, protozoa), enteric viruses, enteropathogenic bacteria, and a variety of systemic or metabolic disturbances.
• •Although there are exceptions, acute diarrhea associated with diet, parasites, and medications generally tends to be mild and self-limiting, whereas acute diarrhea that is severe and life-threatening occurs most frequently in young animals with infectious enteritis (e.g., parvoviral enteritis).
• •Diagnostic evaluations in acute diarrhea need not be extensive. Because treatment is mainly supportive and nonspecific, many animals can be managed without determination of a definitive diagnosis. Nevertheless, it is important to identify parasites and enteropathogens that require specific treatments and to identify surgical diseases (e.g., foreign bodies and intussusception).
• •Treatment of acute diarrhea is based on rehydration therapy and dietary modification. Symptomatic therapy with antidiarrheal agents may be considered. Nonspecific or mild acute diarrhea often is self-limiting in a day or two without treatment or with restricted food intake.

Chronic Diarrhea

• •Diarrhea is categorized as chronic if it has been persistent (3-4 weeks or longer) or has a pattern of episodic recurrence. Chronicity generally excludes simple dietary indiscretion, intoxication, and viral enteritis as causes.

Key Point.

Base management of chronic diarrhea on diagnosis rather than symptomatic treatment. Specific intervention or treatment usually is necessary, requiring a specific diagnosis or functional and histopathologic characterization.

• •The first step in management is to classify the diarrhea as large or small bowel in origin, based on the history and physical examination. Diagnostic tests and procedures include routine hematologic and serum chemistry evaluations, tests of enteropancreatic function, fecal examinations, radiography, ultrasonography, and endoscopy. Biopsy of the small or large intestine may be necessary.

Small Bowel versus Large Bowel

The anatomic localization of the disease process to the small or large bowel is based on the patient's defecation pattern and fecal characteristics (frequency, volume, consistency, color, odor, composition) (Table 69-1 ). This distinction is most useful in dogs for determining the direction of subsequent diagnostic evaluations. Diffuse diseases of the gastrointestinal (GI) tract may produce concurrent small and large bowel signs and, sometimes, gastric signs such as vomiting.

Table 69-1.

SMALL BOWEL VERSUS LARGE BOWEL DIARRHEA

Observation	Small Intestine	Large Intestine
Frequency of defecation	Normal to slightly increased	Very increased
Fecal output	Large volumes	Small volumes frequently
Urgency or tenesmus	Absent	Present
Dyschezia	Absent	Present with rectal disease
Mucus in feces	Absent	Present
Exudate (WBC) in feces	Absent	Present sometimes
Hematochezia (red blood)	Rare	Frequent
Melena (digested blood)	Present sometimes	Absent
Steatorrhea	Present sometimes	Absent
Flatulence and borborygmus	Present sometimes	Absent
Weight loss	Present sometimes	Rare
Vomiting	Present sometimes in dogs; frequent in cats	Occasional

WBC, white blood cells.

Small Bowel Diarrhea

Chronic small bowel diarrhea can be associated with maldigestion and malabsorption and is characterized by a high volume without urgency, tenesmus, or marked increase in frequency. Weight loss and decline in body condition (malnutrition) may occur.

• •Because of unabsorbed nutrients that are degraded and fermented by intestinal bacteria, the feces are rancid and foul-smelling and the increased production of luminal gas by bacteria results in excessive flatulence and borborygmus.
• •Steatorrhea (feces containing an excess of unabsorbed fat) can occur in maldigestive and malabsorptive small bowel diarrhea. In extreme cases, the feces may appear oily, greasy, and pale. Hair around the perineum may also have an oily texture from contact with fatty feces.
• •Small bowel diarrhea is generally free of grossly visible mucus or blood. When there is bleeding from a lesion in the proximal GI tract, the blood pigment becomes dark black during transit (melena). In the absence of gastric bleeding, melena generally indicates small intestinal parasitism (e.g., hookworms), infection (viral, bacterial, fungal), ulceration (e.g., drug induced), severe inflammation, or neoplasia.

Large Bowel Diarrhea

Large bowel diarrhea is characterized by frequent urges to defecate (usually greater than 3 times normal frequency), with each defecation producing small quantities of feces that often contain excessive mucus and sometimes fresh red blood.

• •Urgency resulting from irritability or inflammation of the distal colon causes frequent premature expulsions of small quantities of feces that would otherwise be insufficient to trigger the defecation reflex. Lapses in housetraining (“accidents”) may be caused by urgency and inability to control urges to defecate.
• •Straining (tenesmus) may be noted as the patient remains in position for a prolonged time after defecation or makes repeated attempts to defecate within a few minutes. These attempts may produce little or no feces or sometimes just a few drops of mucus, exudate, and blood.
• •Because many colonic diseases are associated with mucosal injury, inflammation, or ulceration, abnormal fecal constituents are frequently found in large bowel diarrhea, including (1) fresh red blood (hematochezia) that originates from sites of erosion or ulceration, (2) mucus that originates from the abundant goblet cells in the colon that respond to mucosal injury by an outpouring of mucus, and (3) exudate (leukocytes) that originates from the site of inflammation.

Key Point.

Abnormal fecal constituents such as fresh red blood, mucus, and leukocytes are localizing signs indicative of colonic disease.

• •Blood may coat the feces, streaks of blood may be mixed within the feces, or drops of blood may be passed at the end of defecation.
• •Excessive mucus may give the feces a glistening or jelly-like appearance.
• •Exudates are detected by the positive identification of fecal leukocytes using cytology stains.

• •Because the principal function of the colon is absorption of water and electrolytes rather than digestion and absorption of nutrients, nutrient malabsorption and steatorrhea are absent in large bowel diarrhea. Thus, dramatic weight loss and wasting are unlikely if the animal is eating, and the daily fecal output (volume or weight of feces) usually is only minimally increased.
• •Vomiting is a clinical sign in about 30% of patients with colitis.

DIAGNOSTIC APPROACH FOR DIARRHEA

Initial evaluations are aimed at diagnosis of dietary, parasitic, and infectious causes of diarrhea. This should include fecal examinations, therapeutic deworming trials (fenbendazole, 50 mg/kg PO daily for 3 days), and a 4-week dietary trial using a highly digestible commercial or homemade GI diet, either alone (for small bowel diarrhea) or with psyllium added as a fiber source (for dogs with large bowel diarrhea). If diarrhea persists and the cause is not apparent, additional diagnostic evaluations may include a complete blood count (CBC), serum chemistry profile, urinalysis, additional fecal exams for infectious agents (cytology, toxin assay, and cultures), abdominal imaging (radiography and ultrasonography), and enteropancreatic function tests. Finally, endoscopic examination and biopsy may be indicated.

History

The history is especially helpful for localizing the disease process to the small or large bowel. It also may indicate underlying non-intestinal causes of diarrhea (e.g., renal failure, liver disease, hypoadrenocorticism, or feline hyperthyroidism) and identify important predisposing factors such as breed, diet, environmental factors, current medications, and exposure to parasites, infectious agents, and toxins. The following historical aspects of the diarrhea may be diagnostically useful:

• •Mode of onset (abrupt versus gradual)
• •Duration (acute versus chronic)
• •Clinical course (intermittent, continuous, or progressive)
• •Fecal characteristics (small bowel versus large bowel; see previous section)
• •Correlation with diet (food intolerances and dietary indiscretions)
• •Correlation with medication usage (drug side effects)
• •Correlation with stressful events (psychogenic, anxiety, or “irritability” factors)
• •Response to previous treatments (prescribed diets, antibiotics, corticosteroids, or fenbendazole)
• •Association with other signs (weight loss, vomiting, or polyuria-polydipsia)

Key Point.

Consider extraintestinal causes of diarrhea, such as diseases of the pancreas (exocrine pancreatic insufficiency, pancreatitis), liver, kidneys (azotemia), endocrine system (e.g., hypoadrenocorticism and hyperthyroidism), cardiovascular system, and central nervous system (CNS).

Physical Examination

A complete physical examination may reveal important clues about the severity, nature, and cause of diarrhea (Table 69-2 ), although in many patients the findings are nonspecific.

Table 69-2.

PHYSICAL FINDINGS IN INTESTINAL DISEASE

Physical Finding	Potential Clinical Associations
General Physical Examination
Dehydration	Diarrheal fluid loss
Depression/weakness	Electrolyte imbalance, severe debilitation
Emaciation/malnutrition	Chronic malabsorption, protein-losing enteropathy
Dull unthrifty haircoat	Malabsorption of fatty acids, protein, and vitamins
Fever	Infection, transmural inflammation, neoplasia
Edema, ascites, pleural effusion	Protein-losing enteropathy
Pallor (anemia)	Gastrointestinal blood loss, anemia of chronic inflammation
Intestinal Palpation
Masses	Foreign body, neoplasia, granuloma
Thickened loops	Infiltration (inflammation, lymphoma)
“Sausage loop”	Intussusception
Aggregated loops	Linear intestinal foreign body, peritoneal adhesions
Pain	Inflammation, obstruction, ischemia, peritonitis
Gas or fluid distention	Obstruction, ileus, diarrhea
Mesenteric lymphadenopathy	Inflammation, infection, neoplasia
Rectal Palpation
Masses	Polyp, granuloma, neoplasia
Circumferential narrowing	Stricture, spasm, neoplasia
Coarse mucosal texture	Colitis, neoplasia

• •Identify physical findings that may indicate underlying systemic disease that could be a cause or consequence of diarrhea.
• •Identify abnormalities on abdominal palpation of the intestinal loops and digital palpation of the rectum.
• • Inspect the fecal material obtained on the palpation glove for abrasive particles (such as bone chips), blood, and mucus. If indicated, examine the fecal material microscopically for parasites, microorganisms, and inflammatory cells or submit for culture.

Routine Laboratory Tests

• •Evaluate a CBC for leukocyte responses and anemia that may be associated with intestinal disease (Table 69-3).
• •Perform a serum biochemical profile and urinalysis to identify metabolic or systemic disorders that could cause or result from diarrhea (see Table 69-3 ).
• •Measure serum thyroxin (T4) concentration in all cats over 5 years of age with diarrhea or weight loss to exclude hyperthyroidism as a cause (see Chapter 31).

Table 69-3.

LABORATORY FINDINGS IN INTESTINAL DISEASE

Abnormal Laboratory Findings	Clinical Associations
Hematologic Findings
Eosinophilia	Parasitism, eosinophilic enteritis, hypoadrenocorticism, mast cell tumor
Neutrophilia	Bowel inflammation, necrosis, or neoplasia
Neutropenia or “toxic” neutrophils	Parvovirus, FeLV, FIV, endotoxemia, or overwhelming sepsis (e.g., leakage peritonitis)
Monocytosis	Chronic or granulomatous inflammation (e.g., mycosis)
Lymphopenia	Loss of lymphocytes associated with intestinal lymphangiectasia
Anemia	GI blood loss, depressed erythropoiesis (chronic inflammation, neoplasia, malnutrition)
Elevated PCV	Hemoconcentration from GI fluid loss
RBC microcytosis	Iron deficiency (chronic GI blood loss), portosystemic shunt
RBC macrocytosis	RBC regeneration, feline hyperthyroidism, FeLV, nutritional deficiencies (rare)
Serum Biochemical Findings
Panhypoproteinemia	Protein-losing enteropathy
Hyperglobulinemia	Chronic immune stimulation, basenji enteropathy
Azotemia	Dehydration (prerenal), primary renal failure
Hypokalemia	GI loss of fluid and electrolytes, anorexia
Hyperkalemia/hyponatremia	Hypoadrenocorticism, trichuriasis (rare)
Hypocalcemia	Hypoalbuminemia, lymphangiectasia, pancreatitis
Hypocholesterolemia	Lymphangiectasia, liver disease
Elevated liver enzymes or bile acids	Liver disease
Elevated amylase/lipase	Pancreatitis, enteritis, or azotemia
Elevated thyroxine (T4)	Feline hyperthyroidism

FeLV, feline leukemia virus; FIV, feline immunodeficiency virus; GI, gastrointestinal; PCV, packed cell volume; RBC, red blood cell.

Fecal Examinations

Fecal examinations are an important aspect of the diagnostic approach to diarrhea and should involve visual inspection (for blood, mucus, and foreign matter), parasite evaluation, and microscopic examinations. Specialized evaluations can include quantitative fecal collection and fat analysis, chemical determinations, cultures, toxin assays, virology, and nuclear scans, but these are used only in selective cases.

Key Point.

Examination of feces for parasites should be part of the minimum database for all animals with diarrhea.

• •In cases of chronic unresponsive diarrhea, expand the database to include microscopic examination of stained fecal smears for fat, starch, and leukocytes.
• •If circumstances suggest infection, perform fecal culture for specific enteropathogenic bacteria (Salmonella, Campylobacter) or toxin assay for enterotoxigenic Clostridium perfringens.
• •Diagnostic methods for intestinal parasites and infectious agents are listed in Table 69-4 .

Table 69-4.

DIAGNOSIS OF INTESTINAL PATHOGENS OF DOGS AND CATS

Pathogen	Method of Diagnosis
Helminths
Ascarids (Toxocara, Toxascaris leonina)	Routine fecal flotation for ova
Hookworms (Ancylostoma)	Routine fecal flotation for ova
Whipworms (Trichuris vulpis)	Routine fecal flotation for ova; fenbendazole trial
Tapeworms (Taenia, Dipylidium caninum)	Fecal proglottids or flotation for ova
Strongyloides	Fecal sediment or Baermann test for larvae
Others (flukes)	Fecal zinc sulfate centrifugation-flotation for ova
Protozoa
Coccidia (Isospora)	Fecal flotation for oocysts
Cryptosporidium spp.	Microplate ELISA, direct immunofluorescence, PCR, Sheather's flotation
Giardia	Fecal zinc sulfate centrifugation-flotation for cysts; fecal ELISA or IFA; duodenal wash for trophozoites; fenbendazole trial
Tritrichomonas foetus	Fecal wet smear for trophozoites; InPouch TF culture; PCR
Entamoeba histolytica	Fecal wet smear for trophozoites
Balantidium coli	Fecal wet smear for trophozoites
Viruses
Canine parvovirus	Fecal ELISA (SNAP-Parvo Test) for viral antigen (see Chapter 14)
Feline panleukopenia virus	Signs, leucopenia (see Chapter 14)
Canine coronavirus	Fecal EM, virus culture, PCR (see Chapter 14)
Feline enteric coronavirus and FIP	Signs, serology, fecal EM, PCR, biopsies (see Chapter 10)
Rotaviruses	Fecal EM, virus culture, PCR (see Chapter 14)
Astrovirus	Fecal EM, PCR (see Chapter 14)
Canine distemper virus	Signs (see Chapter 13)
Retroviruses (FeLV, FIV)	FeLV antigen test (ELISA, IFA); FIV antibody test (see Chapters 8, 9)
Rickettsia
Salmon poisoning (Neorickettsia helminthoeca)	Operculated trematode eggs in feces; rickettsia in lymph node cytology (see Chapter 17)
Bacteria
Salmonella	Fecal culture
Campylobacter jejuni	Fecal microscopy and culture
Yersinia enterocolitica, Y. pseudotuberculosis	Fecal culture
Bacillus piliformis (Tyzzer's disease)	Biopsy (gut, liver) for filamentous bacteria; mouse inoculation
Mycobacterium spp.	Acid-fast bacteria in cytology/biopsy; culture, PCR (see Chapter 19)
Clostridium perfringens, C. difficile	ELISA-based fecal enterotoxin assays; PCR
Enteropathogenic Escherichia coli (?)	Fecal culture and toxin assays
Fungi
Histoplasma capsulatum	Fungi in biopsies/cytologies; serology (see Chapter 20)
Pythium, Zygomycetes	Pythium ELISA; poorly septate hyphae in biopsies (Chapters 20, 40)
Others (Candida albicans, Aspergillus, etc.)	Yeast or hyphae in biopsies; fungal culture (see Chapters 20, 40)
Algae (Prototheca)	Unicellular algae in cytology or biopsy; fecal culture (Sabouraud's)

ELISA, enzyme-linked immunosorbent assay; EM, electron microscopy; FeLV, feline leukemia virus; FIP, feline infectious peritonitis; FIV, feline immunodefi-ciency virus; IFA, immunofluorescent antibody; PCR, polymerase chain reaction test; Rx, therapeutic response.

Fecal Examination for Parasites

Fecal examination for parasites can include fecal flotation, zinc sulfate centrifugation-flotation, direct wet smears, and immunoassays. Examine fresh feces within 1 hour of collection. Alternatively, refrigerate feces within 1 hour and examine within 3 days, or preserve feces in formalin for later examination.

• • Use routine fecal flotation to identify nematode ova and coccidian oocysts other than Cryptosporidium.
• •In warm, humid regions (e.g., southern United States) endemic for Strongyloides species, perform a direct wet smear, sedimentation, or Baermann procedure to identify larvae in the feces.
• •For Giardia, use zinc sulfate centrifugation-flotation to identify cysts or an immunoassay to identify fecal antigen. Reliable fecal immunoassays are the point-of-care SNAP Giardia Test Kit (IDEXX), the microplate enzyme-linked immunosorbent assay (ELISA) (Remel), or an immunofluorescent antibody (IFA) test at a commercial lab. Evidence suggests the rapid ELISA test for human Giardia is not reliable in animals.
• •Use a direct saline smear of fresh feces to detect motile trophozoites of protozoan parasites, including Giardia, Tritrichomonas, Entamoeba histolytica, and Balantidium coli. This is an insensitive method for diagnosis of Giardia. The distinguishing characteristics of each of these protozoa are discussed under “Protozoan Parasites.”
• •For diagnosis of Tritrichomonas foetus infection in cats, fecal culture using InPouch-TF and fecal polymerase chain reaction (PCR) assay are more sensitive than direct fecal smear microscopy.
• •For Cryptosporidium parvum, a very small coccidian, use fecal antigen immunoassay (microplate ELISA or IFA), Sheather's sugar flotation for oocysts, or modified acid-fast staining. Evidence suggests the rapid ELISA test for human Cryptosporidium is not reliable in animals.
• •Diagnosis of occult parasite infections (e.g., Giardia and most nematodes including whipworms) can be based on response to a therapeutic trial using fenbendazole (50 mg/kg PO q24h for 3-5 days).

Key Point.

Intestinal parasitism can resemble many other small and large bowel disorders. Common examples are hookworms, whipworms, and Giardia.

Fecal Examination for Infectious Agents

The diagnosis of infectious diarrhea often depends on the detection of the offending viral, bacterial, or fungal organisms in the feces. Details of diagnosis of these various enteric infections are found in the respective sections of this chapter.

Viruses

Viral diarrhea is generally acute and is confirmed by detection of viral antigen in the feces (ELISA, PCR, etc.) or virus particles by electron microscopy (see Chapter 14).

Bacteria

The common enteropathogenic bacteria in dogs and cats are listed in Table 69-4.

• •Specific enteropathogenic bacteria, such as Salmonella and Campylobacter, can be isolated from fresh feces using appropriate culture media. Cultures are particularly indicated when examination of fecal cytology preparations reveals the presence of numerous fecal leukocytes or Campylobacter-like bacteria or when there is an outbreak of diarrhea in groups of animals housed together.
• •For diagnosis of Clostridium perfringens and Clostridium difficile enterotoxigenic diarrhea, use validated fecal ELISA (Techlab, Blacksburg, VA) and PCR assays to detect clostridial enterotoxins. The finding of numerous large gram-positive sporulating rods with a “safety pin” appearance in stained fecal smears is not a reliable indicator of toxin-producing C. perfringens. Non-toxigenic C. perfringens is part of the normal intestinal flora in dogs and cats; thus, cultures are not useful.

Fungi and Prototheca

The diagnosis of fungal (Histoplasma, Aspergillus, Pythium, Candida) and protothecal infections is usually based on identification of the organisms in feces or more often in rectal scrapings (Histoplasma), tissue aspirates, or intestinal biopsies (see Chapters 20 and 40).

• •Serodiagnostic tests for presumptive diagnosis of histoplasmosis and pythiosis also are available.
• •Affected tissues can be cultured for systemic fungi and Prototheca (a rare cause of colitis), but culture growth takes weeks and the isolation rate is low.

Fecal Examination Using Special Stains

Feces can be examined microscopically for abnormal constituents using Sudan, Lugol iodine, Gram, and various other cytologic stains. In each test, one to two drops of fresh feces are stained on a microscope slide and examined. In general, these procedures are relatively insensitive and nonspecific and are affected by many factors, including diet.

Sudan and Iodine Stain

Fecal staining with Sudan for undigested fat and Lugol iodine for undigested starch may suggest exocrine pancreatic insufficiency (maldigestion); however, these evaluations are too insensitive, nonspecific, and diet dependent to be recommended. These procedures have been replaced by more reliable diagnostic tests for exocrine pancreatic insufficiency (see Chapter 73).

Cytology Stain

Routine cytology staining (e.g., new methylene blue, Wright, and Diff-Quik stains) identifies fecal leukocytes that are markers of exudative inflammatory colonic disease. Cytology may occasionally identify neoplastic cells or Histoplasma or Prototheca organisms. It is advisable to follow up with patients that are positive for fecal leukocytes with colonoscopy and fecal cultures for invasive bacteria such as Campylobacter and Salmonella.

Gram Stain

With gram staining, the experienced observer may identify large numbers of C. perfringens or Campylobacter-like spiral bacteria; however, microscopy is much less reliable than toxin assays for Clostridium and culture for Campylobacter.

Tests for Fecal Occult Blood

These include a simple, in-office qualitative screening test (Hemoccult test) and a more accurate, semiquantitative send-out test (HemoQuant, SmithKline). These tests are sensitive for detecting even very small amounts of GI hemorrhage. Because of this sensitivity, it is recommended that the owner exclude meat from the animal's diet for at least 3 days prior to testing to avoid false-positive results.

• •The presence of fecal occult blood signifies a bleeding lesion of the GI tract, which suggests an ulcerative, inflammatory, or neoplastic condition, or a hemostatic abnormality.
• •The fecal occult blood test is also indicated to document GI bleeding as a cause of blood loss anemia.

Quantitative Fecal Fat Analysis

This can be used as an intestinal function test to confirm steatorrhea, but it is rarely used because it is cumbersome and impractical to perform and does not differentiate pancreatic maldigestion from intestinal malabsorption. Feces must be collected for a 24- to 72-hour period while the animal is confined and fed a standard diet. The feces are weighed and sent to a commercial laboratory for analysis. Normally, less than 10% of ingested fat is excreted in the feces, or less than 0.3 g/kg/day in dogs and less than 0.4 g/kg/day in cats.

Fecal Proteolytic Activity

Fecal proteolytic activity can be assayed as an indicator of pancreatic secretion of proteases (trypsin) for the diagnosis of exocrine pancreatic insufficiency (EPI). The serum trypsin-like immunoreactivity (TLI) assay is more accurate and is now preferred for the diagnosis of exocrine pancreatic insufficiency in both dogs and cats (see Chapter 73).

Tests for Fecal Protein Loss

See under “Tests for Protein-Losing Enteropathy.”

Enteropancreatic Function Tests

The following tests are designed to evaluate digestive and absorptive functions.

Tests for Exocrine Pancreatic Insufficiency

Tests for exocrine pancreatic insufficiency (pancreatic maldigestion), such as serum trypsin-like immunoreactivity and fecal assays for proteolytic activity, are described in Chapter 73.

Serum Folate and Cobalamin Assays

Serum concentrations of folate and cobalamin (vitamin B₁₂) are indicative exocrine pancreatic function (cobalamin), intestinal absorptive function, and the status of the intestinal bacterial flora.

Serum Folate

Folate, a water-soluble B vitamin, is plentiful in most commercial pet foods, and serum concentration depends primarily on the absorptive function of the proximal small intestine.

• •Serum folate (normal, dog: 6.5-11.5μg/L; cat: 9.7-21.6μg/L) may be decreased in enteropathies that impair absorption in the proximal small intestine or in diffuse small intestinal disease. Widespread malignancy and sulfasalazine treatment also may decrease serum folate.
• •Serum folate may be increased with overproliferation of the normal intestinal flora because many species of bacteria synthesize folic acid.
• •Serum folate also may be increased by high dietary intake of folic acid, low intestinal pH, exocrine pancreatic insufficiency (32% of cases), and artifactually by hemolysis or heating of the blood specimen.

Serum Cobalamin

Cobalamin, a water-soluble B vitamin, is plentiful in most commercial pet foods, and serum concentration depends on the secretion of pancreatic intrinsic factor necessary for normal cobalamin absorption and on the absorptive function of the ileum.

• •Serum cobalamin (normal, dog: 249-733 ng/L; cat: 290-1500 ng/L) is frequently decreased in exocrine pancreatic insufficiency (deficiency of intrinsic factor) and in enteropathies that impair absorption in the distal small intestine, including diffuse small intestinal disease. It also is decreased in presumed small intestinal bacterial overgrowth.
• •Because cobalamin has a shorter half-life in cats, cats with chronic intestinal disease are particularly susceptible to developing cobalamin deficiency.
• •Prolonged exposure of the blood specimen to bright light may artifactually decrease cobalamin.
• •An isolated hereditary defect in cobalamin absorption has been recognized in some dog breeds (giant schnauzer, Border collie, Shar-Pei).

Key Point.

In small intestinal bacterial overgrowth, serum folate may be increased due to synthesis of folate by the proliferated bacteria, whereas cobalamin may be decreased because bacteria can utilize or bind the vitamin, making it unavailable for absorption.

Breath Hydrogen Test

This assesses monosaccharide or disaccharide malabsorption or bacterial overgrowth, based on the principle that intestinal bacteria ferment intraluminal carbohydrate and produce hydrogen gas, some of which is absorbed into the blood and excreted by the lungs. This test is impractical for routine clinical use and is affected by diet, gastric emptying, intestinal transit, and the status of the intestinal flora.

Five-Sugar Absorption Tests for Intestinal Permeability

These oral sugar absorption tests are variations on the other carbohydrate absorption tests. A mixture of sugars is used as a noninvasive molecular probe of mucosal permeability and injury based on urine recovery (in a 6-hour urine sample) after oral administration. These sugar probes measure passive diffusion. Lactulose, cellobiose, and raffinose are probes of the large pores of the paracellular pathway, and urine recovery increases with mucosal epithelial damage. Mannitol and rhamnose are probes of the numerous small pores of the transcellular pathway, and urine recovery decreases with loss of mucosal absorptive surface area (such as villous atrophy). An increase in the lactulose-to-rhamnose ratio is typical of intestinal disease with mucosal damage and increased permeability.

One variation on this procedure involves giving a mixture of lactulose, rhamnose, xylose, methylglucose, and sucrose, and the ratios are determined in 6-hour urine for lactose-to-rhamnose (permeability test), xylose-to-methylglucose (absorption test), and sucrose-to-methylglucose (mucosal digestion test).

In addition to reflecting absorptive function and permeability, results are also affected by gastric emptying, intestinal dilution and transit, systemic distribution, metabolism, and renal clearance. Results have not shown good correlation with clinical disease activity and histologic findings.

Unreliable Absorption Tests

In general, the reliability of oral absorption tests is affected by gastric emptying time, intestinal dilution and transit time, digestion and absorption, systemic distribution, metabolism, and renal excretion. Because of inconsistent results, the following absorption tests are not considered clinically useful in dogs and cats:

• •Absorption of glucose substrates (glucose, lactose, starch)—Affected by insulin, etc.
• •Xylose absorption—For detection of brush border monosaccharide malabsorption
• •Quantitative fecal fat analysis—For detection of fat malabsorption (steatorrhea)
• •Oral triglyceride absorption
• •Vitamin A absorption
• •Bentiromide para-aminobenzoic acid (BT-PABA) absorption

Tests for Protein-Losing Enteropathy

Excessive GI loss of plasma proteins can be documented using fecal assays that quantitate the intestinal loss of specific serum proteins, such as alpha-1-proteinase inhibitor, or an IV dose of 51 chromium-labeled albumin, a radiopharmaceutical.

• •Alpha-1-proteinase inhibitor is a serum protein similar in molecular size to albumin. The intestinal loss of alpha-1-proteinase inhibitor in protein-losing enteropathy parallels the loss of albumin, except that it is not digested and is excreted intact in the feces. Thus, using a canine-specific assay, alpha-1-proteinase inhibitor can be measured in the feces as a marker for intestinal protein loss in dogs. This test is useful for evaluation of dogs with unexplained hypoproteinemia and for early detection of affected dogs in high-risk breeds, such as the soft-coated wheaten terrier.
• •Normal fecal excretion of the alpha-1-proteinase inhibitor is <5.7μg/g feces in dogs and <1.6μg/g feces in cats. The assay requires submission of three fresh fecal specimens to the Gastrointestinal Laboratory, Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843-4474 (website: http://www.cvm.tamu.edu/gilab).

Tests for Bacterial Overgrowth

Direct evidence of small intestinal bacterial overgrowth is conventionally based on quantitative cultures of small intestinal juice; however, because of extensive overlap in the bacterial counts found in normal and diarrheic dogs and cats, the diagnostic criteria for small intestinal bacterial overgrowth in animal patients is uncertain. Indirect evidence of small intestinal bacterial overgrowth is indicated by the following:

• •Increased serum folate and decreased serum cobalamin, reflecting increased bacterial metabolic activity
• •Abnormal hydrogen breath test results, reflecting increased bacterial fermentation activity
• •Increased serum unconjugated bile acids, reflecting increased bacterial deconjugation activity
• •Idiopathic chronic small bowel diarrhea that is antibiotic responsive

Tests for Intestinal Motility

Tests for clinically assessing intestinal motility have limited clinical usefulness except for identifying obstruction to flow. These include intestinal transit time of barium, barium-impregnated spheres, or radiopharmaceuticals. The hydrogen breath indirectly reflects transit time of the proximal GI tract.

Radiography and Ultrasonography

Plain Abdominal Radiography

Plain radiography is indicated for detection of intestinal masses or abnormal gas-fluid patterns, especially when mechanical or obstructive disorders are suspected (e.g., intestinal mass, foreign body, or intussusception).

Gastrointestinal Barium Contrast Radiography

Upper GI barium radiography is indicated when other evaluations fail to determine the cause of small bowel diarrhea or when intestinal obstruction is suspected (see Chapter 4). This may help detect obstructive lesions, neoplastic masses, and inflammatory lesions that cause an irregular mucosal pattern or distortion of the bowel wall. In most cases, however, diarrhea involves microscopic and functional changes in the bowel that are not detected by barium radiography.

Barium Enema Contrast Radiography

Barium enema radiography is indicated in selected cases of large bowel diarrhea for evaluating the colon and cecum for intussusceptions, neoplasms, polyps, strictures, inflammatory lesions, and colonic displacement or malformation. Colonoscopy is generally preferred over barium enema for evaluating the colon because it yields more definitive diagnostic information.

Abdominal Ultrasonography

Ultrasonography is indicated for assessing intestinal wall thickness and layering, for defining intestinal and other abdominal masses, and for evaluating other abdominal organs—e.g., lymph nodes, spleen, pancreas, liver, biliary tract, kidneys, adrenals, and prostate (see Chapter 4).

Endoscopy

Key Point.

Endoscopic examination with mucosal biopsy is required for definitive diagnosis or accurate characterization of the disease in many cases of chronic intractable diarrhea in which non-intestinal, dietary, parasitic, and infectious causes have been excluded.

Gastrointestinal Endoscopy

Duodenoscopy with a flexible fiberoptic endoscope can be performed in the anesthetized animal for visual examination of the upper GI tract, including duodenum; for duodenal aspiration (for quantitative bacterial culture or detection of Giardia trophozoites); and for directed forceps biopsy of the intestinal mucosa (see Chapter 67 for a description of endoscopic equipment and discussion of gastroscopy).

• •The normal duodenal mucosa appears pale pink with a uniformly granular villus pattern.
• •Biliary and pancreatic duct papillae and Peyer lymphoid patches are normally seen.
• •The mucosa is non-friable and should be free of excessive granularity, hemorrhages, erosions, ulcers, thickened folds, masses, or strictures. Villous lymphatics (lacteals) should not be prominent in the fasted animal.
• •The lumen is easily and uniformly distensible with air.

Colonoscopy

Colonoscopy allows direct visualization of the lumen of the colon, sampling of luminal content for culture and exfoliative cytology, and directed forceps biopsy of the ileocolic mucosa.

• •Suitable rigid colonoscopes are relatively inexpensive and easy to use. Because colonic diseases are often diffuse, examination and biopsy of the descending colon with a rigid instrument is sufficient for diagnosis in many patients.
• •When lesions are located predominantly in the ascending or transverse colon, areas inaccessible with a rigid colonoscope, use a flexible fiberoptic or video colonoscope. A flexible colonoscope can be navigated through the ileocolic sphincter for examination and biopsy of the ileum in some animals.
• •The normal colonic mucosa appears pale pink through the colonoscope and reflects light uniformly. It is non-friable, thin enough that the submucosal vessels are visible, and free of erosions, ulcers, thickened folds, masses, or strictures.

Intestinal Biopsy

The least invasive and, in many cases, preferred method for procurement of intestinal biopsies is endoscopy. If endoscopy is not available, or if endoscopic biopsies are inconclusive, consider full-thickness intestinal biopsy by laparotomy (see Chapter 70).

• •Obtain multiple biopsies along the length of the gut even if no lesions are visible by gross inspection, which is often the case.
• •Biopsy mesenteric lymph nodes and evaluate other abdominal organs, especially the pancreas, liver, and colon.
• •Duodenal aspirates or duodenal mucosal impression smears may be examined for Giardia trophozoites or cultured quantitatively for aerobic and anaerobic bacterial overgrowth.

Therapeutic Trials

In some cases, the response to a dietary modification or therapeutic drug trial is used as an empirical diagnostic approach, when supported by adequate clinical information. Common therapeutic trials are given in the sections that follow.

Diet Modification

• •Commercial GI diet for optimal digestability
• •Novel protein diet—For dietary hypersensitivity or food allergy
• •Fiber supplemented diet—For fiber-responsive large bowel diarrhea (dogs)

Fenbendazole

• •For helminths (especially whipworms)
• •For Giardia

Metronidazole

• •For Giardia
• •For enteropathogenic bacteria (especially Clostridium)
• •To suppress flora in bacterial overgrowth
• •To treat idiopathic inflammatory bowel disease (via flora effects or immune modulation)

NONSPECIFIC TREATMENT OF DIARRHEA

Dietary, supportive, and symptomatic therapy often is beneficial in diarrhea, especially acute diarrhea. In severe acute diarrhea, fluid and electrolyte therapy can be lifesaving.

Dietary Management

Acute Diarrhea

• •The initial goal is to physiologically “rest” the GI tract by restricting food intake for at least 24 hours.
• •When resuming feeding, give bland, low-fat foods in small amounts at frequent intervals. Various commercial diets are available that have been specially formulated for animals with GI disease. Recipes for appropriate homemade diets are available as well. Examples of appropriate foods include boiled rice combined with turkey, boiled skinless chicken, yogurt, or low-fat cottage cheese as protein sources.
• •Examples of commercial “intestinal diets” appropriate for nonspecific therapy of diarrhea include Eukanuba Low Residue (Iams), Prescription Diet i/d (Hill's), Low Fat (Waltham), and EN Formula (Purina). Other highly digestible diets can also be used.
• •When the diarrhea has been resolved for 48 hours, gradually reintroduce the animal's regular diet.

Chronic Diarrhea

Divide daily food intake into three or four feedings, and use (1) commercial diets designed for GI disease with high digestibility and mild fat restriction (for all types of diarrhea); (2) novel protein diets (for dietary hypersensitivity and inflammatory bowel disease); or (3) fiber-enriched diets (for canine large bowel diarrhea).

Fluid Therapy

• •In severe, acute diarrhea, such as occurs with parvoviral enteritis, fluid and electrolyte replacement is essential for management of intestinal fluid loss that may lead to serious dehydration, shock, and death (see Chapter 5).
• •Parenteral methods of fluid therapy are preferred in most cases; however, over-the-counter oral glucose-electrolyte solutions (Pedialyte) are available for counterbalancing intestinal fluid losses in cases of mild diarrhea.

Antidiarrheal Drugs

Symptomatic treatment is based on drugs that modify motility, fluid secretion, and absorption or on drugs that act locally within the lumen as protectants or adsorbents.

• •In most cases, these drugs are reserved for short-term use, usually for periods of 5 days or less. Some commonly used antidiarrheal drugs and their dosages are listed in Table 69-5 .
• •The purposes of antidiarrheal drugs are to provide short term relief from diarrhea, to provide relief from bowel discomfort (“crampiness”), and to control intestinal fluid losses.

Table 69-5.

DRUGS USED FOR SYMPTOMATIC TREATMENT OF DIARRHEA

Drug	Product (Manufacturer)	Preparation	Dosage	Frequency
Narcotic Analgesics*
Diphenoxylate	Generic	Tab: 2.5 mg	0.1–0.2 mg/kg PO	q6–8h
		Liq: 0.5 mg/ml
Loperamide	Imodium AD (McNeil)	Cap: 2 mg	0.1–0.2 mg/kg PO	q6–8h
		Liq: 0.2 mg/ml
Codeine	Many	Tab, Cap, Liq	0.25–0.5 mg/kg PO	q6–8h
Anticholinergics/Antispasmodics
Aminopentamide	Centrine (Fort Dodge)	Tab: 0.2 mg	0.01–0.03 mg/kg SC, IM, PO	q8–12h
		Inj: 0.5 mg/ml
Dicyclomine	Generic	Tab: 20 mg	0.2 mg/kg PO	q8–12h
		Cap: 10 mg
Propantheline	Generic	Tab: 15 mg	0.25 mg/kg PO	q8–12h
Hyoscyamine	Levsin (Schwarz)	Tab: 0.125 mg	0.003–0.006 mg/kg	q8–12h
		Liq: 0.025, 0.125 mg/ml	PO, SC
Antisecretory/Protectant
Bismuth subsalicylate†	Pepto-Bismol (Procter & Gamble)	Liq: 9, 16 mg/ml	0.5–1.0 ml/kg PO	q6–8h

^*Narcotic analgesics are not recommended in bacterial enteritis or liver disease.

^†Avoid long-term (>3 days) use in cats because of low tolerance for salicylates. Cap, capsules; Inj, injectable; Liq, elixir, suspension, or drops; Tab, tablets.

Opiate and Opioid Narcotic Analgesics

Key Point.

Opioid drugs such as loperamide are the most effective all-purpose antidiarrheal agents (see Table 69-5).

• • Examples include loperamide (Imodium A-D), diphenoxylate (Lomotil), paregoric, morphine, and codeine.
• •Opioids delay gastric emptying and slow bowel transit by stimulating non-propulsive contractions while decreasing propulsive motility (peristalsis), thereby allowing more contact time for absorption. This promotes fluid and electrolyte absorption.
• •Opioids inhibit intestinal fluid loss through modification of mucosal fluid and electrolyte transport.
• •Opioids increase anal tone and reduce the discomfort (i.e., crampiness) associated with acute diarrhea.
• •Side effects are bloating, cramping, constipation, vomiting, and CNS depression. Use is not recommended with invasive bacterial enteritis.

Anticholinergic Drugs

• •Examples include aminopentamide (Centrine), dicyclomine, and propantheline.
• •They cause a generalized suppression of all gut motility, including beneficial non-propulsive motility, that may lead to unwanted ileus. The atropine-like antispasmodic action may be beneficial for controlling the urgency and discomfort of anorectal disease in some cases.
• •They inhibit intestinal fluid loss, presumably through an antisecretory effect.
• •Side effects are GI paralysis (ileus), worsening of diarrhea, constipation, tachycardia, xerostomia, urinary retention, ocular effects, and CNS stimulation.

Protectants and Adsorbents

• •Examples include kaolin-pectin (Kaopectate), bismuth (Pepto-Bismol), aluminum and magnesium salts, activated charcoal, cholestyramine, and barium.
• •These oral agents remain in the lumen, and they are proposed to adsorb or bind harmful bacteria and bacterial toxins and to provide a protective coating on inflamed mucosal surfaces.
• •The efficacy of these drugs is controversial. There is little evidence that they diminish intestinal fluid losses. Large doses are often required, and they are difficult for owners to administer.

Anti-inflammatory Therapy

Non-infectious inflammatory bowel diseases are often treated with corticosteroids or nonsteroidal anti-inflammatory agents (NSAIDs).

Corticosteroids

• •Examples include prednisone, prednisolone, dexamethasone, and budesonide.
• •Corticosteroids have anti-inflammatory, antisecretory, and mucosal-stimulating properties. The primary indication is for inflammatory bowel disease.

Nonsteroidal Anti-inflammatory Drugs

• •Bismuth subsalicylate (Pepto-Bismol) has a mild mucosal anti-inflammatory action in the lumen of the proximal GI tract. Efficacy for small animal diarrhea is infrequent.
• •Preparations of 5-aminosalicylic acid (5-ASA) (mesalamine) are poorly absorbed in the proximal GI tract so that they reach the colon where colonic bacteria release the active drug to produce a mucosal anti-inflammatory action for treatment of chronic colitis. Examples include sulfasalazine (Azulfidine), olsalazine (Dipentum), encapsulated mesalamine (Asacol), polymer-coated mesalamine (Pentasa), and mesalamine enema (Rowasa).
• •Avoid systemic nonsteroidal anti-inflammatory drugs (e.g., flunixin meglumine, ibuprofen, and aspirin) in dogs and cats with GI disease, or use them cautiously because they cause GI ulceration.

Antibiotic Therapy

Do not use antibiotics routinely as empirical therapy in cases of uncomplicated diarrhea of undetermined cause because of the adverse effects of antibiotics on the normal intestinal flora and the risk of promoting resistant strains of bacteria.

• •Use well-chosen antibiotics when specific bacterial enteropathogens, such as Salmonella, Campylobacter, or enterotoxigenic C. perfringens, are suspected.
• •Antibiotics are appropriate in conditions associated with severe mucosal damage and a high risk of secondary sepsis or endotoxemia, such as parvoviral enteritis and hemorrhagic gastroenteritis (HGE). Thus, indications for antibacterial therapy in animals with acute GI disease include bloody diarrhea, fever, leukocytosis, leukopenia, fecal leukocytes, and shock.
• •
  Metronidazole is an antibiotic frequently used in animals with diarrhea. Its potential indications are as follows:

  • •
    To treat Giardia (and various other protozoa)
  • •
    To treat certain enteropathogenic bacteria, such as Clostridium species
  • •
    To suppress overabundant enteric flora in small intestinal bacterial overgrowth
  • •
    To modify normal enteric flora that may play a role in chronic inflammatory bowel disease
  • •
    To immunomodulate in chronic inflammatory bowel disease

Fenbendazole-Responsive Diarrhea

Fenbendazole (50 mg/kg PO q24h for 3 days) is highly effective for treating common intestinal nematode and Giardia infections.

Cobalamin Therapy

Cobalamin (vitamin B₁₂) is vital for many cellular processes, and it is frequently depleted in patients with chronic small intestinal disease or exocrine pancreatic insufficiency. Cobalamin deficiency can impair intestinal mucosal regeneration and cause villous atrophy and malabsorption, exacerbating diarrhea and contributing to anorexia and depression in patients with chronic GI disease.

• •Treat with parenteral cobalamin (1000μg/ml) when serum levels are decreased, especially if <200 ng/L. Give injections weekly for at least 6 weeks, then every other week for 6 weeks, and then monthly.
• •For cats and small dogs: Give 250μg SC, weekly
• •For medium dogs: Give 500μg SC, weekly
• •For large dogs: Give up to 1000μg SC, weekly

DIETARY DIARRHEA

Etiology

• •Diarrhea as a result of indiscriminant eating and chewing behavior is particularly common in dogs. Dietary indiscretions include overeating, ingestion of spoiled garbage or decomposing carrion, and ingestion of abrasive or indigestible foreign material (e.g., bones, stones, hair, plants, wood, cloth, carpeting, foil, or plastic) that can traumatize the GI mucosa.
• •Diarrhea may result from an abrupt change in diet. Any change in the composition of the diet should be made in gradual increments over a period of several days to allow adaptation.
• •Animals may be intolerant of certain foods, such as lactose ingested as milk, fatty foods, spicy foods, and food additives found in certain commercial diets. Food hypersensitivity to specific protein sources is implicated as a cause of inflammatory bowel disease in dogs and cats.
• •Fiber-responsive diarrhea is sometimes seen in dogs.

Diagnosis

Dietary causes of diarrhea usually are identified by careful history-taking and the response to a restricted diet.

• •Carefully question the owner about all aspects of diet and environment, including recent changes in type and brand of food, all supplemental feeding practices using “people foods,” patterns of chewing behavior involving non-food items (including toys, plants, and haircoat), likelihood of garbage ingestion, and potential for unobserved indiscretions in free-roaming animals.
• •Examine the feces for abrasive particles.

Treatment

Dietary diarrhea is self-limiting with feeding of a restricted diet, elimination of identifiable offending substances from the diet, and prevention of indiscriminant eating or chewing behavior. Management of dietary hypersensitivity is discussed under “Chronic Inflammatory Bowel Disease” later in this chapter.

DRUG- AND TOXIN-INDUCED DIARRHEA

Etiology

• •Diarrhea is a frequent adverse side effect of many medications, including nonsteroidal anti-inflammatory agents (e.g., aspirin, ibuprofen, indomethacin, phenylbutazone, and flunixin meglumine), digitalis and other cardiac drugs, dithiazanine (Dizan), magnesium-containing compounds, lactulose (for hepatic encephalopathy), some anthelmintics, most anticancer drugs, and many antibacterial drugs (partly from adverse effects on the flora).
• •Dexamethasone has been associated with hemorrhagic gastroenterocolitis characterized by erosion, ulceration, necrosis, and sometimes fatal colonic perforation, especially in dogs treated for intervertebral disc disease.
• •Many exogenous toxins cause diarrhea, including biologic toxins such as the enterotoxins that cause staphylococcal and clostridial food poisoning and various diarrheogenic chemical poisons, such as heavy metals (lead, arsenic, thallium), insecticides (organophosphate dips, flea treatments), lawn and garden products (insecticides, herbicides, fungicides), and some houseplants.
• •Free-roaming animals may drink from stagnant or runoff water polluted or potentially contaminated with toxic industrial, petroleum, or agricultural chemicals.

Diagnosis

Suspect drug- and toxin-induced diarrhea on the basis of history of exposure (or opportunity for exposure), clinical signs, and exclusion of other causes of diarrhea.

• •Many medications and most toxins that cause diarrhea also cause vomiting.
• •Some toxicities are associated with various extraintestinal signs (e.g., neurologic manifestations of lead and organophosphate toxicity).

Treatment

• •Drug-induced diarrhea usually resolves after discontinuation of the offending medication or a reduction in its dosage.
• •Toxin-induced diarrhea resolves with symptomatic antidiarrheal therapy, prevention of further exposure to the toxin, and gradual elimination of the substance from the body. However, if the exact toxin is known, consult other sources of information for additional specific treatments and antidotes.

INTESTINAL PARASITES (HELMINTHS)

The majority of intestinal parasite infections are asymptomatic: when clinical signs do occur, diarrhea and weight loss are most common. Young growing animals generally are more frequently and severely parasitized, but never overlook endoparasitism as a possible cause of acute or chronic diarrhea of either small or large bowel type in dogs and cats of all ages. Other intestinal diseases, such as viral or bacterial enteritis, often are complicated by intestinal parasite infection.

The diagnosis of parasitism depends on the identification of eggs, cysts, larvae, trophozoites, or proglottids in the feces (see Table 69-4). Parasites that are notorious for evading detection include Giardia in dogs and cats with small bowel diarrhea and whipworms in dogs with large bowel diarrhea. In such cases, response to a therapeutic trial is an indirect method of diagnosis. Anthelmintics used to treat the common parasites are listed in Table 69-6 .

Table 69-6.

ANTHELMINTICS FOR DOGS AND CATS

			Efficacy
Drug	Product (Manufacturer)	Dosage	Ascarids	Hook-worms	Whip-worms	Tape-worms
Dichlorophene	Many products	Dog: Capsule size as directed	++	++	−	+
Diethylcarbamazine*	Many products	Dog: 6.6 mg/kg daily or 110 mg/kg once PO	++	−	−	−
Epsiprantel	Cestex (Pfizer)	Dog: 5.5 mg/kg PO	−	−	−	+++
		Cat: 2.75 mg/kg PO
Febantel plus praziquantel and pyrantel	Drontal-Plus (Bayer)	15 mg/kg of febantel	+++	+++	+++	+++
Fenbendazole	Panacur (Intervet)	50 mg/kg PO for 3–5 days	+++	+++	+++	++†
Ivermectin*‡	Heartgard Plus (Merial)	Dog: 6 mg/kg PO monthly	++	++	−	−
Milbemycin oxime*	Interceptor, Sentinel (Novartis)	Dog: 0.5 mg/kg PO monthly	++	++	++	−
Piperazine	Many products	110 mg/kg PO	++	−	−	−
Praziquantel	Droncit (Bayer)	See label; PO, SC, IM	−	−	−	+++
Pyrantel pamoate	Nemex (Pfizer)	10 mg/kg PO if <2.5 kg, 5 mg/kg PO if >2.5 kg	+++	+++	−	−

+++, excellent efficacy; ++, good efficacy; +, minimal efficacy.

^*Drugs used concomitantly as heartworm preventatives (see Chapter 152).

^†Efficacious for Taenia species of tapeworms only; not effective against Dipylidium caninum.

^‡Consult package insert because of special safety precautions or potential for serious side effects.

Ascarids

Etiology

Ascarid nematodes are the most prevalent intestinal parasites of dogs and cats worldwide. The ascarids of the dog are Toxocara canis and the less common Toxascaris leonina; those in the cat are Toxocara cati and Toxascaris leonina.

Life Cycle

Ascarid infection occurs by four routes:

• •Prenatal infection results from transplacental migration, which occurs only with T. canis. Many puppies are born infected with ascarids because of transplacental migration of the bitch's somatic T. canis larvae into the fetus (prenatal infection).
• •Milk-borne infection results from transmammary migration, which occurs with both T. canis and T. cati. Milk-borne infection during nursing is the major source of ascariasis in kittens.
• •Infection by ingestion of infective eggs occurs with all three ascarids (T. canis, T. cati, and T. leonine).
• •Infection by ingestion of a paratenic (transport) host (T. canis, T. cati) or an intermediate host (T. leonina).

Three types of migration pattern occur when an animal is infected:

• •Liver-lung migration (T. canis, T. cati)
• •Migration within the wall of the GI tract (all three ascarids)
• •Somatic tissue migration (T. canis, T. cati)

Clinical Signs

• •Signs of ascariasis occur most often in young puppies and kittens, in which the adult worms in the small intestine may cause abdominal discomfort, whimpering and groaning, potbellied appearance, dull haircoat, unthriftiness, stunted growth, and diarrhea. Worms frequently are passed in vomitus or diarrhea.
• •Rarely, large, tangled masses of worms occlude the lumen in young pups and cause death from in-testinal obstruction, intussusception, or intestinal perforation.
• •In the neonatal pup, the migration of large numbers of T. canis larvae through the lungs can cause severe damage and fatal pneumonia.
• •In young animals with light infections and in adults, infection is most commonly asymptomatic or is evidenced merely by a loss of body condition.

Diagnosis

• •The diagnosis of ascariasis is readily established by the identification of ascarid eggs in routine fecal flotation.
• •Most pups begin passing large numbers of eggs in their feces around 3 weeks of age and continue to shed eggs for most of early puppyhood (4-6 months) until treated.

Treatment

• •Numerous effective anthelmintics for ascarids are available (see Table 69-6). Pyrantel pamoate is especially well tolerated and effective in puppies and kittens; it also is effective in controlling hookworms.
• •Because many pups are born infected with T. canis, treatment is recommended at 2 weeks of age, before eggs are first passed in the feces, and repeated at 4, 6, and 8 weeks to kill all worms derived from prenatal, milk-borne, and ingestion routes of infection.
• •Toxocaral visceral larva migrans (VLM) is a serious disease of humans (especially children) produced by the invasion of visceral tissues by migrating T. canis; thus, infected pups are considered public health hazards.

Hookworms

Etiology

• • Ancylostoma caninum, the most common hookworm in the dog, is a voracious bloodsucker.
• • Ancylostoma tubaeforme, the common hookworm in the cat, is more of a tissue feeder than a bloodsucker and is far less pathogenic than A. caninum in dogs.
• • Ancylostoma braziliense (southern United States) and Uncinaria stenocephala (Canada) affect both dogs and cats but are less common than A. caninum and A. tubaeforme and are only mildly pathogenic.

Life Cycle

Hookworm infection can occur by five routes: prenatal, milk-borne, ingestion of infective larvae (L3), skin penetration by infective larvae, and ingestion of paratenic hosts. Ingestion and cutaneous migration probably are the most common routes of infection. With all routes of infection, eggs are passed in feces after 2 to 3 weeks.

Clinical Signs

Pathogenicity is directly related to the hookworm's bloodsucking activity and capacity for causing intestinal blood loss. Hookworms embed their mouthparts in the mucosa to suck blood and tissue fluid, leaving bleeding, punctiform ulcers as they “graze.” Hence, an important consequence of severe hookworm infection is blood loss anemia.

• •The clinical signs of ancylostomiasis include tarry (melena) or bloody diarrhea accompanied by pallor, weakness, emaciation, and dehydration.
• •Rapidly progressive blood loss anemia may result in acute death of neonates. In other animals, chronic blood loss may cause iron deficiency anemia characterized by erythrocytes that show hypochromasia and microcytosis.
• •Acute, pruritic dermatitis occasionally is associated with the active penetration of skin by hookworm larvae.
• •Hookworm infections in mature animals often are asymptomatic.

Diagnosis

Young dogs are most often affected, and the diagnosis usually is readily established by identification of the characteristic Strongyloides hookworm ova by routine fecal flotation. Ancylostomiasis often is associated with eosinophilia on the CBC.

Treatment

Anthelmintics effective for eradicating hookworms include pyrantel pamoate (safest for young animals), fenbendazole, and febantel (see Table 69-6 for product names and dosages).

• •In areas in which A. caninum is a frequent problem, routinely treat bitches and pups. Because of prenatal and milk-borne infection, initiate treatment of pups at 2 weeks of age, along with treatment for T. canis.

Key Point.

Pyrantel pamoate suspension is an excellent anthelmintic for nursing pups because it is safe and is active against both hookworms and ascarids.

• •Severely anemic animals should receive whole blood transfusions, iron supplementation, and supportive therapy as needed.

Prevention

• •Parasite control is aided by good sanitation and impervious flooring in kennels and dog runs.
• • Various commercial products have a combined effect as preventive agents against both heartworms and hookworms (e.g., milbemycin) (see Table 69-6).

Whipworms

Etiology

The canine whipworm, Trichuris vulpis, is a common cause of large bowel diarrhea in dogs in many areas. The adult nematode has a predilection for the proximal colon and cecum, where its distinctive threadlike head end, or “whip,” firmly embeds deep within the mucosa to feed on blood and tissue fluids, thereby causing colitis and typhlitis.

The feline whipworms, Trichuris campanula and Trichuris serrata, are rare and usually are not associated with clinical signs.

Life Cycle

• •Whipworm infections occur by ingestion of infective ova, and the life cycle is direct.
• •The prepatent period is approximately 3 months. Ova may survive and remain infectious in the environment for 4 to 5 years; hence, contaminated ground is probably the major reservoir of infection.

Clinical Signs

• •Whipworms infect dogs of all ages. Although there may be minimal clinical signs in light infestations, trichuriasis frequently causes acute, chronic, or intermittent signs of mucoid large bowel-type diarrhea with urgency and sometimes hematochezia.
• •Pseudohypoadrenocorticism, characterized by hyperkalemia and hyponatremia in the presence of normal adrenal function, has been associated with severe whipworm diarrhea in several dogs.

Diagnosis

• •Definitive diagnosis of whipworm infection requires identification of the characteristic brown, bipolar-operculated, football-shaped ova by routine fecal flotation.
• •Repeated fecal examinations may be necessary to identify ova because of the unusually long prepatent period and because it is not uncommon for active infection to be characterized by prolonged periods when ova are not shed in the feces.
• •
  Alternative means of diagnosis of ova-negative, or so-called occult, infections, include the following:

  • •
    Colonoscopic observation of adult whipworms in the bowel lumen
  • •
    Resolution of signs in response to a therapeutic trial of fenbendazole or febantel

Treatment

• •Give fenbendazole or febantel for 3 days (see Table 69-6). In refractory cases, a 5-day course is recommended. Routinely repeat treatment at 3 weeks and 3 months, because whipworms are difficult to eradicate.
• •Rarely, trichuriasis has been associated with severe transmural granulomatous typhlitis that may be palpable as a tender right-midabdominal mass. This lesion may be refractory to anthelmintics and require typhlectomy.

Prevention

• •Because it is virtually impossible to eradicate the parasite from infected ground, frequent reinfection is a common problem. For this reason, collect and properly dispose of feces whenever possible.
• •In dogs with frequent access to ground that has been heavily contaminated with whipworm ova (a common situation in many public parks and backyards), reinfection is so frequent that retreatment every 2 to 3 months may be necessary.
• •Disinfect concrete runs with dilute sodium hypochlorite bleach.

Strongyloides

Etiology

Strongyloides are tiny (2 mm) rhabdoid nematodes found in warm, humid tropical regions such as the southern Gulf states of the United States.

• •In dogs, strongyloidiasis is caused by Strongyloides stercoralis, a parasite that burrows in the mucosa of the proximal small bowel.
• •In cats, strongyloidiasis is caused by Strongyloides tumefaciens, a parasite that burrows within the mucosa of the large intestine.

Life Cycle

• •Infection with third-stage larvae is by the oral or cutaneous route, and adult worms develop in the small intestine following migration in the circulation and lung.
• •Parthenogenetic female adults produce eggs that hatch within the gut lumen so that first-stage (rhabdoid) larvae are passed in the feces. These larvae may develop into infectious third-stage (filariform) larvae or free-living adults.

Clinical Signs

• • S. stercoralis is mainly a problem in pups, in which it causes acute hemorrhagic enteritis that is often fatal.
• • S. tumefaciens infection in cats is usually asymptomatic, but in some cats the parasite causes peculiar tumor-like, white, nodular (2-3 mm) proliferations in the colonic mucosa and submucosa that are associated with chronic diarrhea and debilitation.

Diagnosis

• •Ova containing first-stage Strongyloides larvae can be identified in feces by flotation techniques. Free larvae (0.8 to 1.6 mm long × 30 to 80μm) may be identified by direct microscopic examination of fresh feces or by the Baermann technique.
• •In cats, the diagnosis of S. tumefaciens also can be established by colonoscopic observation and biopsy of mucosal nodules filled with adult worms.

Treatment

Treat with fenbendazole (50 mg/kg/day PO for 5 days), diethylcarbamazine (100 mg/kg PO once), or pyrantel pamoate (20 mg/kg/day PO for 5 days).

Tapeworms

Etiology

• •The most common tapeworm (cestode) of dogs and cats is Dipylidium caninum. Fleas and lice are intermediate hosts.
• •Several species of Taenia can be acquired by dogs and cats (most commonly Taenia pisiformis in the dog and Taenia taeniaeformis in the cat) from ingestion of cysticercus-infected tissues from intermediate hosts (e.g., rabbits, rodents, sheep, and ungulates).
• •Other cestodes that are less common include Echinococcus, Multiceps, Mesocestoides, and Spirometra.

Clinical Signs

• •Tapeworms that parasitize the small bowel of dogs and cats are relatively harmless, rarely causing more than a subtle decline in body condition.
• •The proglottids of D. caninum are highly motile and may cause anal pruritus as they crawl on the perineum; crawling proglottids are often detected by observant owners in the animal's stool or on the perineum.

Diagnosis

• •Tapeworms are diagnosed by the identification of proglottids or ova in the feces.
• • D. caninum proglottids are distinguished from Taenia spp. by their barrel shape and double genital pore. Also, a proglottid can be squashed in a drop of water between a slide and a cover slip to identify the characteristic D. caninum egg capsules that contain up to 20 eggs.

Treatment

• •Praziquantel and epsiquantel are the most effective all-around drugs for treatment of cestodiasis (see Table 69-6).
• •Fenbendazole is effective against Taenia species but not D. caninum.
• •Flea and lice control is important for preventing D. caninum reinfection. Control of predation and scavenging helps prevent infection with other cestodes.

PROTOZOAN PARASITES

Coccidia

Etiology

Canine and feline intestinal Coccidia are protozoan parasites that belong to the genera Isospora, Besnoitia, Hammondia, Sarcocystis, Neospora, Toxoplasma, and Cryptosporidium. Most enteric coccidial infections of dogs and cats are commensal and nonpathogenic.

• •Primary enteric disease in small animals has been described only with Isospora and Cryptosporidium.
• • Toxoplasma gondii and Neospora caninum are multisystemic infections discussed in Chapter 21.
• • Isospora spp. that infect dogs include I. canis, I. ohioensis, I. burrowsi, and I. neorivolta; I. felis and I. rivolta infect cats.

Life Cycle

• •Intestinal coccidiosis occurs most commonly by ingestion of infective (sporulated) oocysts from a feces-contaminated environment. Cryptosporidium infection is often water borne.
• •Infection occurs occasionally from ingestion of infective cyst-containing tissues of paratenic (transport) hosts such as rodents and other prey and ingestion of uncooked meat of herbivores.

Clinical Signs

• •Coccidiosis in most animals is an asymptomatic, incidental infection.
• • Coccidia are opportunists. Clinical disease is usually related to massive oocyst ingestion in newborn animals and is associated with overcrowded, unsanitary, high-stress conditions in settings such as pet shops, kennels, shelters, catteries, and laboratory colonies. Concurrent disease, malnutrition, and immunosuppression are predisposing factors.
• •Cryptosporidiosis has complicated canine distemper, feline leukemia virus, feline immunodeficiency virus, and advanced neoplasia.
• • Clinical disease usually is characterized by diarrhea that varies from soft to fluid and is occasionally mucoid or bloody. Other signs can include vomiting, lethargy, weight loss, and dehydration. Coccidia have been associated with chronic malabsorption.

Diagnosis

Isospora Coccidia

• •Coccidiosis is diagnosed by the identification of oocysts in fresh feces.
• •Because many normal dogs and cats harbor intestinal coccidia and these protozoa are generally regarded as minimally pathogenic, the clinical significance of finding coccidial oocysts often is questionable.

Cryptosporidium

• •Fecal immunoassay is the preferred method for diagnosis of Cryptosporidium. The direct immunofluorescence test (Merifluor, Meridian) and microplate ELISA (ProSpecT, Remel) are most reliable; however, false-negative reactions may occur with some strains.
• •Fecal PCR is also used but is not widely available.
• • Cryptosporidium oocysts can be isolated for identification from feces using concentration techniques, such as Sheather's sugar flotation or formaldehyde-ether sedimentation, or by staining feces with Kinyoun carbol fuchsin stain or modified acid fast stain. Cryptosporidia oocysts are so small (as little as one-tenth the size of common Isospora oocysts) that careful examination of slides under oil immersion is necessary to visualize these tiny structures.
• •Histologic or electron microscopic identification of Cryptosporidium in intestinal biopsies is another means of diagnosis.

Treatment

Identification of oocysts in a healthy animal with normal feces indicates a self-limiting commensal infection and does not necessarily warrant treatment, although treatment may help reduce environmental contamination with oocysts.

Treatment for Isospora

If clinical signs are attributed to coccidiosis, as in young puppies and kittens with diarrhea, treat with one of the following coccidiostats:

• •Sulfadimethoxine—50 to 60 mg/kg/day PO for 1 to 3 weeks
• •Trimethoprim-sulfA&Mdash;15 to 30 mg/kg q12-24h PO for 1 week
• •Furazolidone—8 to 20 mg/kg/day PO for 1 week
• •Amprolium (unapproved for use in dogs but often recommended for treating animals in kennels or other groups of dogs)—20% powder in gelatin capsules, 100 mg q24h for small-breed pups or 200 mg q24h for larger-breed pups, PO for 7 to 12 days; alternatively, 1/4 tsp of 20% powder per four pups mixed with puppy ration or 1 ounce (30 ml) of 9.6% solution per gallon of free-choice water

Treatment for Cryptosporidiosis

Cryptosporidiosis is generally self-limiting in immunocompetent hosts. The infection may be persistent in severely immunocompromised animals or humans.

• •The drug of choice for treating Cryptosporidium is azithromycin (Zithromax, 7-15 mg/kg PO q12h for 5-7 days).
• •Other suggested antibiotics include clindamycin and tylosin, but efficacy is questionable. Nitazoxamide has been used but causes severe vomiting. Paromomycin has been used but causes acute renal failure and deafness.
• •Because Cryptosporidium are not species specific, zoonotic transmission between animals and humans can occur, sometimes with fatal consequences in the presence of severe immunosuppression. Case studies have implicated pets as a source of human infection.

Giardia

Giardia are pear-shaped, binucleated, flagellated protozoa that infect the small intestine, where they may interfere with mucosal absorption, and sometimes produce diarrhea. There are two forms: motile trophozoites that inhabit the intestinal tract and non-motile infective cysts that are passed through the feces into the environment.

Motile trophozoites attach to the brush border surface of the mucosal epithelium by means of ventral cup-shaped suction discs or float free within the adjacent mucus layer. They are mainly found in the duodenum in the dog and in the jejunum and ileum in the cat.

Life Cycle

The life cycle of Giardia is direct, and the usual source of infection is the ingestion of food or water contaminated with cysts. Wild animals are potential reservoirs. The prevalence is highest in young animals and animals confined together in groups.

Clinical Signs

• •The majority of Giardia infections are subclinical, especially in mature animals.
• •Clinically apparent giardiasis occurs most frequently in young dogs and cats and is characterized by intestinal malabsorption with large volumes of foul-smelling, light-colored, watery or cow patty–like diarrhea, steatorrhea, and weight loss. Diarrhea may be acute or chronic, intermittent or continuous, and self-limiting or persistent.
• • The severity of giardiasis is enhanced by concomitant viral, bacterial, or helminth infections.

Diagnosis

• •Fecal immunoassays for Giardia antigen are accurate and convenient. Reliable immunoassays include the point-of-care SNAP Giardia Test Kit (IDEXX), the microplate ELISA (Alexon Trend), or a direct immunofluorescence test available at commercial labs. Evidence suggests that the rapid ELISA test intended for humans is not reliable in animals.
• •Microscopic diagnosis of giardiasis depends on identification of cysts (oval, 8 to 12μm × 7 to 10μm) by zinc sulfate centrifugation-flotation of feces or of motile flagellated trophozoites (pear-shaped, 9 to 21μm × 5 to 15μm × 2 to 4μm) in fresh diarrheic feces suspended in saline or in duodenal specimens (aspirates, brushings, or impression smears of mucosal biopsies).

Key Point.

Giardia cysts are identified in feces much more frequently than trophozoites. Negative fecal examinations do not exclude a diagnosis of giardiasis.

• •Consider a therapeutic trial of fenbendazole or metronidazole when diagnostics are negative and “occult” giardiasis is suspected.

Treatment

Drugs that are effective for treating giardiasis include metronidazole, fenbendazole, albendazole, febantel, quinacrine, and furazolidone.

Key Point.

Fenbendazole is the initial treatment of choice for giardiasis.

• •Fenbendazole (Panacur) (50 mg/kg PO q24h for 3 days) is very safe and effective for treating Giardia in dogs and probably cats.
• •Febantel (Drontal Plus, 15 mg/kg q24h for three doses or a single dose of 30 mg/kg PO) appears to be effective but needs further study.
• •Metronidazole (25-30 mg/kg PO q12h for 5-10 days) is usually effective, although up to one-third of infections may be metronidazole resistant. Side effects include anorexia, vomiting, and reversible CNS toxicity (weakness, ataxia, disorientation, seizures, and blindness).
• •Albendazole (Valbazen) (25 mg/kg PO q12h for 5 days in cats and 2 days in dogs) is effective but has been associated with severe bone marrow toxicity. For this reason, fenbendazole is preferred.
• •Furazolidone (Furoxone, SmithKline) (4 mg/kg PO q12h for 5 days) is effective and convenient for cats, as it is available in a suspension form.

Prevention

Failure to respond to treatment is often the result of repeat exposure and recurrence of infection, especially in groups of animals confined together.

• •Decontaminate the environment with quaternary ammonia.
• •Bathe animals to remove cysts from the haircoat.
• •Treat all animals that are confined together.
• • Giardia vaccine is available but is not recommended. It does not prevent infection. It may reduce cyst shedding, but this is inconsistent.

Tritrichomonas foetus in Cats

Tritrichomonas foetus is a frequent cause of mild to severe lymphoplasmacytic colitis and chronic large intestinal diarrhea in young cats, especially cats confined in crowded cattery conditions.

Clinical Signs

The diarrhea may wax and wane and is semiformed or “cow pie” in consistency and malodorous. It may contain blood or mucus. The diarrhea often improves transiently in response to antibiotics. Affected cats generally remain otherwise healthy and in good body condition. Diarrhea is often exacerbated by concurrent enteric infections or parasites, especially Giardia and Cryptosporidium.

Diagnosis

The diagnosis can be confirmed by direct fecal microscopy, fecal culture, or PCR assay.

• •Motile trophozoites of Tritrichomonas foetus can be identified in fresh fecal wet smears taken directly from the rectum in about 14% of cases. The likelihood of detecting trophozoites is lower in formed feces, desiccated feces, or in cats recently treated with antibiotics.
• •Fecal culture is more sensitive for diagnosis than microscopy. Culture requires 0.05 g of freshly voided feces inoculated in special media (InPouch TF, BioMed Diagnostics). The instructions on using this culture system are found at the website below.
• •Fecal PCR assay is the most accurate test (high sensitivity and specificity) for detecting T. foetus, and information on submitting samples is found at http://www.cvm.ncsu.edu/mbs/gookin_jody.htm.
• •Trichomonads may be observed in the superficial mucus and crypts in colonic biopsies.

Treatment

T. foetus is virtually impossible to eradicate with antibiotics. Numerous antibiotic agents have been evaluated without success. Treatment can reduce the number of organisms and improve clinical signs, but it usually does not eliminate the infection.

• • Diarrhea often improves with antibiotics but relapses when antibiotics are stopped.
• •Other measures include reducing housing density, reducing stress, improving diet, and treating concurrent infections such as Giardia and Cryptosporidium.
• •The long-term prognosis is good based on findings that most infected cats resolve the clinical signs of T. foetus infection within 2 years (median, 9 months). However, many of these cats remain subclinically infected for several years. Clinical disease may be prolonged in cats living under dense housing conditions, possibly attributable to stress.

Entamoeba

E. histolytica, primarily a human pathogen, rarely may cause amebic colitis (bloody-mucoid diarrhea) in dogs and cats that drink polluted water.

Diagnosis

Diagnosis is based on identification of ameboid trophozoites with pseudopodial movement in saline smears of fresh diarrheic feces, amebic cysts in zinc sulfate flotation of formed feces, or trophozoites in colon biopsies.

Treatment

Optimal treatment for amebic colitis in dogs and cats is unknown, but response has been seen with metronidazole (25-30 mg/kg PO q12h for 5-10 days) or furazolidone (2.2 mg/kg PO q8h for 7 days).

Balantidium

B. coli, a ciliated protozoan that primarily infects swine, is a rare cause of chronic ulcerative colitis in dogs.

Diagnosis

Diagnosis is based on identification of large (40 to 80μm × 25 to 45μm), oval, brown, rapidly swimming ciliated trophozoites with prominent macronuclei in saline suspensions of fresh feces or identification of protozoal cysts in zinc sulfate or sedimentation preparations of feces.

Treatment

Optimal treatment is unknown, but metronidazole (25-30 mg/kg PO q12h for 5-10 days) appears to be effective.

VIRAL INFECTIONS OF THE INTESTINES

Canine Intestinal Viruses

• •Canine parvovirus, coronavirus, and rotavirus cause viral enteritis and diarrhea in dogs. Canine parvovirus is an acute, severe, highly contagious enteritis that is prevalent worldwide. Coronavirus and rotavirus are less prevalent and cause relatively mild clinical signs except in neonates. For details concerning intestinal viruses, see Chapter 14.
• •Because of its epitheliotropism, canine distemper virus also causes diarrhea (see Chapter 13).

Feline Intestinal Viruses

• •The most clinically important primary enteric virus is feline panleukopenia virus (FPV), a parvovirus. Other feline intestinal viruses include enteric coronavirus, rotavirus, and astrovirus (see Chapter 14).
• •The intestine may be involved as part of generalized viral infections such as feline leukemia virus (see Chapter 8), feline immunodeficiency virus (see Chapter 9), and feline infectious peritonitis, a coronavirus (see Chapter 10).

BACTERIAL INFECTIONS OF THE INTESTINES

Most enteropathogenic bacteria produce intestinal disease by invading the epithelium (invasive bacteria) or by liberating diarrheogenic enterotoxins (non-invasive or enterotoxigenic bacteria).

Enteropathogenic bacteria of clinical importance include Salmonella species, Campylobacter jejuni, C. perfringens, and C. difficile. Yersinia species and Bacillus piliformis are rare and are not discussed here. Salmonella and Campylobacter are primarily invasive, causing mucosal damage that leads to inflammation, exudation, mucus secretion, and bleeding. Bacterial enterotoxins may also play a role in the pathogenesis of these agents. C. perfringens and C. difficile are noninvasive and cause diarrhea by an enterotoxigenic mechanism.

Key Point.

Because Salmonella, Campylobacter, and Yersinia also are potentially zoonotic pathogens, pets occasionally are reservoirs for human infection.

Salmonella

Etiology

• •Salmonellosis is caused by gram-negative bacilli belonging to the genus Salmonella of the family Enterobacteriaceae. Salmonella frequently are isolated from the feces of normal dogs and cats, but clinical signs of salmonellosis are uncommon, indicating a prevalent asymptomatic carrier state.
• • Salmonella infection is transmitted by the fecal-oral route, mainly through ingestion of contaminated food or water. The organisms can survive in the environment for long periods outside the host; thus, fomite transmission also can occur.
• •Infected migratory birds have been a source of fatal infections in cats, and raw meat, bone, and raw food diets have recently been implicated in canine infections.
• •Infection risk depends on infectivity of the strain, size of the inoculum, competition from the established flora, age of the host, and host defense factors. Infection rates are greatest in young animals and in group confinement situations with overcrowding and poor sanitation.

Clinical Signs

Manifestations of Salmonella infection may be categorized into three syndromes: subclinical carrier state, enterocolitis, and enterocolitis with bacteremia. Virulence of the bacterial strain and host susceptibility play roles in the severity of infection.

• •Clinical salmonellosis is relatively uncommon compared with the prevalence of the subclinical carrier state.
• • Salmonella enterocolitis is characterized by acute watery or mucoid diarrhea (containing blood in severe cases), vomiting, tenesmus, fever, anorexia, lethargy, abdominal pain, and dehydration. Most animals recover in 3 to 4 weeks, although shedding of organisms often persists up to 6 weeks and sometimes persists longer.
• • Salmonella can cause chronic or intermittent diarrhea in some animals.
• •Rarely, Salmonella enterocolitis progresses to a potentially fatal bacteremia or endotoxemia with signs of systemic inflammatory response syndrome, shock, and disseminated intravascular coagulation (DIC).

Diagnosis

Suspect salmonellosis in animals that develop acute diarrhea and have identifiable risk factors, such as known or probable exposure, young age, immune deficiency, debilitating illness, or housing in overcrowded or unsanitary conditions.

• •
  Nosocomial outbreaks with high morbidity and mortality have been recorded in hospitalized animals, the greatest risk occurring in the following animals:

  • •
    With severe illness
  • •
    Undergoing major surgery
  • •
    Hospitalized for 5 or more days
  • •
    Receiving glucocorticosteroids, anticancer chemotherapy, or oral antibiotics (especially ampicillin) that upset the normal flora
• •Routine diagnostic tests usually are noncontributory, except that a degenerative neutropenia may be found in severe cases with bacteremia and endotoxemia. Feces may contain leukocytes.
• •Confirmation of the diagnosis depends on isolation of Salmonella spp. from properly cultured fecal specimens or from blood cultures in bacteremic animals.

Treatment

The use of antibiotics in the treatment of salmonellosis is controversial. Salmonella invasion that is confined locally to the mucosa produces enterocolitis that is self-limiting and is not likely to be affected by antibiotics.

Key Point.

Antibacterial therapy, especially oral, non-absorbable antibiotics that alter the flora, may actually prolong shedding of Salmonella organisms and encourage development of a prolonged convalescent carrier state.

Antibiotics are indicated when Salmonella invasion becomes severe or complicated by bacteremia and endotoxemiA&Mdash;as indicated by signs such as shock, dehydration, high fever or hypothermia, and extreme depression—or by laboratory findings such as azotemia, electrolyte imbalances, neutropenia, hypoglycemia, hypoproteinemia, or coagulopathy. Peracute onset and severe hematochezia may also be an indication of impending systemic invasion and should prompt antibiotic therapy.

• •Base antibiotic selection on culture and sensitivity testing. Most isolates are susceptible to enrofloxacin (Baytril, Bayer) (dog: 5 mg/kg PO q12h; cat: 2.5 mg/kg PO q12h), trimethoprim-sulfa (15 mg/kg PO q12h), or chloramphenicol. Administer antibiotics for 7 to 10 days and reculture feces 1 and 4 weeks after treatment.
• •In addition to antibiotics, fluid and electrolyte replacement and identification and correction of underlying predisposing conditions are important aspects of therapy.
• •Proper hygiene in handling of infected animals is necessary to prevent fecal-oral or fomite transmission of infection to other animals or to humans.

Prognosis

• •The prognosis for most animals with salmonellosis is good, although the mortality rate can be high in outbreaks in extremely susceptible populations (e.g., hospital patients and neonates).
• •Prognosis is guarded to poor for animals with extremely bloody diarrhea, fever > 104°F or hypothermia, neutropenia with a left shift, and indications of sepsis with multiorgan failure (DIC, hypoglycemia, azotemia, jaundice).

Campylobacter

C. jejuni organisms are fastidious, microaerophilic, gram-negative, motile, slender, and curved bacteria that are important pathogens of animals and humans worldwide.

Etiology

Many clinically normal dogs and cats shed Campylobacter in their feces. Isolation rates vary widely, from less than 1% in confined pet populations to 50% or more in some animal shelters. Thus, conditions of close confinement and poor sanitation apparently provide the greatest opportunity for exposure. The majority of Campylobacter-positive dogs are clinically normal carriers.

Clinical Signs

Because it is difficult to produce enteritis with Campylobacter experimentally in dogs and cats and because many of the animals that harbor these organisms are asymptomatic, it has been debated whether Campylobacter by itself causes diarrhea in dogs and cats unless superimposed on other enteropathogenic infections with viruses, other bacteria, Giardia, or helminths.

• •Clinical signs associated with Campylobacter infection in dogs and cats have been attributed to superficial erosive enterocolitis or enterotoxin-mediated secretory diarrhea. Clinical signs are characterized by watery-mucoid diarrhea, with or without blood and fecal leukocytes, lasting 5 to 15 days and may be accompanied by vomiting or tenesmus.
• •Fever is usually mild or absent.
• •In some animals the diarrhea appears to be chronic or intermittent.

Diagnosis

• •
  Presumptive diagnosis of campylobacteriosis can be made by fecal microscopy; however, this requires an experienced examiner, because spirochetes and other motile bacteria that are part of the normal flora may be mistaken for Campylobacter. The presence of fecal leukocytes may also be noted.

  • •
    Campylobacter-like organisms are identified as slender, curved, gram-negative rods that are characteristically W-shaped in stained fecal smears and as highly motile, darting, spiral, or S-shaped bacteria in fresh saline fecal smears examined by dark-field or phase-contrast microscopy.
• • Definitive diagnosis requires isolation of Campylobacter from fresh feces using special selective media. Since Campylobacter organisms are microaerophilic and difficult to isolate, obtain fecal specimens for culture directly from the rectum and place them in anaerobic transport media immediately after collection.

Treatment and Prognosis

• •Effective antibiotics include erythromycin (10-15 mg/kg PO q8h for 7 days; vomiting is a frequent side effect), enrofloxacin (for dogs, Baytril at 5 mg/kg PO q12h for 7 days), or azithromycin (Zithromax at a dosage of 7-15 mg/kg PO q12h for 5-7 days).
• •Antibiotics may not eliminate fecal shedding of the organisms, which can persist up to 4 months. Repeat fecal cultures 1 and 4 weeks after treatment.
• •Because contact with feces from infected animals is a potential source of infection for humans as well as for other animals, advise owners of infected pets to take standard precautions such as proper disposal of potentially infectious feces, hand washing after handling infected animals, and separating infected animals from infants and small children until post-treatment cultures confirm that infection has been eliminated.
• •The prognosis is considered good, although rare fatalities in dogs and cats have been reported.

Clostridium perfringens

Etiology

Enterotoxigenic C. perfringens is an important cause of acute and chronic diarrhea in dogs and cats. C. perfringens is a large, anaerobic, gram-positive bacillus that normally exists in the intestinal tract of most dogs and cats. Enterotoxin-producing strains of C. perfringens can be associated with nonspecific episodes of diarrhea, acute hemorrhagic diarrhea, chronic or recurrent diarrhea, and outbreaks of diarrhea in animal groups.

These bacteria normally reside in the bowel in the vegetative form, but they can release their toxin during sporulation endogenously within the bowel or exogenously in contaminated food. The cpe gene that regulates production of C. perfringens enterotoxin (CPE) is up-regulated by factors that activate sporulation; thus, the presence of clostridial endospores in feces or food has been suggested as an indirect marker for the presence of CPE. Whether derived endogenously or ingested, CPE causes diarrhea by binding to intestinal epithelium and causing increased permeability, hypersecretion, and cell damage (cytotoxicity).

Endogenous sporulation and the production of CPE can be associated with alteration of the intraluminal environment caused by sudden changes in diet, antibiotic administration, alkaline conditions, immunosuppression, inflammatory bowel disease, or concurrent intestinal infections.

Clinical Signs

Enterotoxigenic C. perfringens infection is associated with diarrhea that varies from watery to soft and may contain mucus or blood. Increased frequency is common, and tenesmus may be seen.

• •In dogs, enterotoxigenic C. perfringens has also been associated with a syndrome of acute hemorrhagic gastroenteritis accompanied by severe hemoconcentration.
• •Infection can also cause diarrhea in groups of animals confined together and nosocomial outbreaks in hospitalized animals.
• • Clostridial diarrhea is usually self-limiting after a few days, but in some animals diarrhea can persist chronically for weeks to months. Some animals have recurrent episodes of diarrhea.

Diagnosis

Routine hematologic and serum chemistry evaluations are usually normal in animals with clostridial diarrhea. Colonoscopy is not routinely necessary in these cases, but endoscopic findings are usually nonspecific (diffuse hyperemia, increased friability, fresh bleeding, and increased mucus). Biopsies range from minimal abnormalities to catarrhal, lymphoplasmacytic, or suppurative colitis.

A definitive diagnostic test for C. perfringens-induced diarrhea is lacking. Further work is needed to determine the role of CPE in canine and feline diarrhea and to define the optimal diagnostic parameters for clostridial diarrhea. Fecal spore counts in stained fecal smears are commonly used for routine cage-side screening; however, studies have not shown a correlation between spore counts and positive assays for CPE or a correlation between either of these diagnostic procedures and the presence or absence of diarrhea. In people, fecal assays for CPE are considered more accurate than spore counts; however, the commercially available CPE assays used in people need to be validated for dogs and cats. In principle, CPE assays should be valid across species.

• •The identification of more than five clostridial endospores per oil immersion field (identified by their “safety pin” appearance with Diff-Quik or Wright staining) is considered by many to be presumptive evidence for a diagnosis of enterotoxigenic diarrhea caused by C. perfringens. Clostridial spores are generally larger than other bacilli found in feces. Malachite green can be used as a special stain for endospores. Fecal leukocytes also may be present. Unfortunately, the appearance or absence of clostridial spores in the feces does not correlate well with CPE assays or signs; thus, it might be advisable to take into account spore counts, CPE assays, and clinical information before making a diagnosis of clostridial diarrhea.

Key Point.

Fecal ELISA assay for CPE is generally more reliable and specific than fecal spore counts.

• •Commercial fecal assays for CPE are available in kit form for testing humans. The ELISA test (C. perfringens Enterotoxin Test; Techlab, Blacksburg, VA) appears to be the most reliable in dogs. Another commercial test, reverse passive latex agglutination (RPLA Kit, Oxoid), is insensitive and nonspecific in dogs and thus is not recommended. Use fresh feces only and transport without delay to the laboratory in prechilled diluent at 4°C (freezing should be avoided), because the fecal toxin breaks down after 24 hours.
• •Cultures are not useful because non-toxigenic C. perfringens is part of the flora in normal dogs and cats and cultures do not reliably distinguish toxigenic and non-toxigenic strains.
• •Assays using molecular probes and PCR are being evaluated as improved diagnostic procedures for enterotoxigenic C. perfringens.

Treatment

Diarrhea caused by enterotoxigenic C. perfringens can be effectively treated with ampicillin (20 mg/kg PO q8h), amoxicillin-clavulanate (12-25 mg/kg PO q12h), tylosin (20-40 mg/kg PO q12h), or clindamycin (5-10 mg/kg PO q12h) for 5 to 7 days. Metronidazole (10-20 mg/kg PO q12h) can also be effective but seems to work less consistently.

• •Clostridial diarrhea is usually self-limiting or responsive to antibiotics in 2 to 3 days; however, chronic or recurrent clostridial diarrhea may require long-term antibiotics (e.g., tylosin once daily or every other day) and a fiber-supplemented diet to prevent relapses.
• •Commercial fiber-containing diets or regular diets supplemented with psyllium (Metamucil at a dosage of 1-2 tbsp/day for dogs) may help reduce bacterial proliferation and sporulation because fiber is fermented to short-chain fatty acids that acidify bowel contents. Alkaline rather than acid conditions are most favorable for C. perfringens. In addition, short-chain fatty acids nourish colonic epithelium and protect against injury.

Clostridium difficile

C. difficile is an anaerobic, gram-positive, spore-forming bacillus. Toxigenic C. difficile and its toxin have been isolated from normal dogs and cats and occasionally from animals with mild diarrhea or acute hemorrhagic diarrhea; however, this organism does not appear to be a frequent enteropathogen in dogs and cats. Pseudomembranous colitis as seen in people is not seen in dogs and cats.

Diagnosis

C. difficile can be cultured using selective medium; however, the organism is isolated from normal dogs as well, and culture alone does not confirm the production of diarrheogenic toxins.

Commercial ELISA kits that detect both toxins A and B in feces are recommended, but validation in dogs and cats is needed.

Treatment

Use metronidazole for treatment of suspected or confirmed C. difficile infections.

FUNGAL INFECTIONS OF THE INTESTINES

Mycotic infections of the bowel are uncommon; however, fungi are opportunists that capitalize on predisposing factors such as lowered host resistance, malnutrition, antecedent debilitating illness, and prolonged therapy with antimicrobials or corticosteroids. Fungi may cause acute, dysentery-like diarrhea or chronic diarrhea accompanied by emaciation.

Causes of mycotic intestinal disease include Histoplasma capsulatum, Pythium spp., Aspergillus spp., Candida albicans, and other saprophytes. Histoplasmosis is a multisystemic mycotic infection and is discussed in Chapter 20. Intestinal aspergillosis and candidiasis are rare and discussed briefly in Chapter 20.

Intestinal Pythiosis and Zygomycosis

Various poorly septate saprophytic molds and fungi that include Pythium insidiosum (pythiosis) and several genera of Zygomycetes (zygomycosis) can deeply invade the tissues of the GI tract. These infections were formerly misnamed phycomycosis.

Pythiosis is most common and is seen in young, large-breed dogs that live in the southern Gulf states of the United States. Rare feline cases are characterized by ulcerative gastroenteritis.

Clinical Signs

Pythium and Zygomycetes can infect any part of the digestive tract, but lesions most commonly involve the stomach, small intestine, mesentery, and mesenteric lymph nodes, resulting in an extensive granulomatous tissue reaction.

• •Signs include chronic intractable diarrhea and vomiting, anorexia, depression, and progressive weight loss.
• •Bowel necrosis and ulceration may cause bloody diarrhea in some cases.
• •Regions of extensive granulomatous inflammation may produce palpable enteromesenteric masses.
• •The infection may disseminate beyond the GI tract to other abdominal viscera.

Diagnosis

• •Physical examination may reveal an abdominal mass or marked regional thickening of the bowel.
• •The CBC may reveal mild to moderate non-regenerative anemia and mild neutrophilia, with or without a left shift.
• •Routine abdominal radiography frequently demonstrates an abdominal mass. Ultrasonography and barium contrast GI radiography often delineate a thickened, stenosed segment of bowel.
• •A sensitive and specific ELISA test for presumptive diagnosis of pythiosis is available.
• •Confirmation depends on histologic identification of broad, non-septate or sparsely septate hyphae in biopsies of the stomach, intestine, or abdominal lymph nodes. The organisms stain with Gridley or methenamine silver stains and are found mostly within the necrotic regions of granulomas in the submucosa and muscularis mucosa.
• •Differentiate intestinal pythiosis from other granulomatous and neoplastic proliferations of the GI tract, including histoplasmosis, lymphoma, and regional (granulomatous) enteritis.
• •The extensive tissue reaction can easily be mistaken for neoplasia at laparotomy (or necropsy); thus, careful histologic evaluation including use of fungal stains is essential for accurate diagnosis.

Treatment

Because these fungi are resistant to standard antifungal drugs, the most effective treatment is radical surgical excision of the severely involved segments of bowel (for surgical technique, see Chapter 70). Some animals with pythiosis have been treated successfully with itraconazole and terbinafine in combination or with lipid-complexed amphotericin B as described in Chapter 20. The prognosis is guarded to poor.

INTESTINAL PROTOTHECOSIS

Etiology

Prototheca spp. are ubiquitous unicellular algae that may rarely colonize the lamina propria and submucosa of the intestinal tract of dogs and cause severe necrotizing or ulcerating enterocolitis.

Clinical Signs

• •The algae appear to have a predilection for initially invading the colon, resulting in signs of chronic large bowel diarrhea with hematochezia.
• •The organisms typically disseminate widely throughout the body and most frequently involve other visceral organs, the eyes, and the CNS.
• •Only a cutaneous form has been described in cats.

Diagnosis

• •Colonoscopy reveals thickened, corrugated mucosal folds that may be friable or ulcerated.
• •Organisms can be identified in feces, cytology preparations (Wright or Gram stain), and biopsies (Gomori or periodic acid-Schiff stain) as clusters of endosporulated, ovoid structures (5-16μm in length).
• • Prototheca can also be cultured on Sabouraud's cycloheximide-free dextrose media.

Treatment

Successful treatment of systemic protothecosis in animals is rare. A combination of IV lipid-complexed amphotericin B with itraconazole is suggested (see Chapter 20 for pharmacology and dosages).

CHRONIC INFLAMMATORY BOWEL DISEASE

The term inflammatory bowel disease (IBD) refers to a diverse group of chronic enteropathies characterized by idiopathic infiltration of the GI tract mucosa and (sometimes) submucosa with inflammatory cells. The infiltration may involve the stomach, small intestine, colon, or a combination of these and is classified on the basis of the predominant cell type as lymphocytic-plasmacytic, eosinophilic, neutrophilic, granulomatous, or histiocytic. A mixture of inflammatory cells in some lesions makes classification difficult.

Lymphocytic-Plasmacytic Inflammatory Bowel Disease

Etiology

• •Lymphocytic-plasmacytic IBD is by far the most common form of IBD in both dogs and cats. The etiology is not determined in most cases; however, genetic, dietary, bacterial, immunologic, and mucosal permeability factors have been implicated.
• •The pathogenesis of lymphocytic-plasmacytic IBD may involve a mucosal hypersensitivity reaction to antigens from food, intestinal bacteria, or the intestinal tract itself. This may result from a primary disorder of the intestinal immune system and its regulation or from immune events that occur secondary to mucosal injury and permeability. Chronic inflammation of the bowel may become self-perpetuating when loss of mucosal integrity allows bacterial or dietary proteins to enter the lamina propria, where they incite further immune reaction and inflammation.
• •Genetic factors appear to be involved in predisposing certain breeds to lymphocytic-plasmacytic IBD (e.g., German shepherd, basenji, soft-coated wheaten terrier, and Shar-Pei). Basenjis develop a severe form of IBD (also called immunoproliferative enteropathy) that is thought to be related to a genetic disorder of immune regulation, is progressive in nature, and is exacerbated by stress.

Clinical Signs

The most common signs of IBD are vomiting, diarrhea, and weight loss. The signs vary with the region of the GI tract affected and the severity of the mucosal disease. The clinical course is typically waxing and waning and can go on for months to years. Dogs and cats of all ages are affected.

• • Lymphocytic-plasmacytic enteritis causes chronic diarrhea and weight loss. Vomiting occurs more frequently in cats with IBD.
• • Lymphocytic-plasmacytic colitis causes chronic large bowel diarrhea characterized by increased frequency of defecation, urgency, tenesmus, increased fecal mucus, and hematochezia. Fecal consistency varies. Intermittent hematochezia may be the only sign of IBD in some cats.
• •Signs may be intermittent or persistent. In severely affected dogs, protein-losing enteropathy (ascites, hydrothorax, edema) can occur.
• •Some animals with a biopsy diagnosis of lymphocytic-plasmacytic enteritis that fail to respond to treatment or that later relapse and deteriorate rapidly are found to have diffuse intestinal lymphoma.

Diagnosis

Precise criteria for the diagnosis of IBD have not been established. In general, the clinical criteria for diagnosis are (1) chronic signs of GI disease, (2) characteristic mucosal lesions of IBD in endoscopic biopsies, (3) failure to respond to dietary trials, and (4) exclusion of known causes of chronic inflammation of the intestinal tract based on thorough diagnostic evaluation. This last criterion emphasizes that IBD is a diagnosis of exclusion and not a catch-all label to be used as a substitute for diagnostic evaluation. Because lymphocytic-plasmacytic inflammation is a nonspecific lesion, only a thorough diagnostic workup can establish that it is truly idiopathic and not merely an inflammatory response to an undiagnosed condition.

• •In the diagnostic evaluation, exclude parasitic (Giardia, Tritrichomonas, canine whipworms), infectious (Campylobacter, Salmonella, Histoplasma) and other causes of chronic intestinal inflammation.
• •The differential diagnosis of lymphocytic-plasmacytic IBD includes dietary hypersensitivity, small intestinal bacterial overgrowth, intestinal lymphoma, intestinal lymphangiectasia, and the other histologic types of chronic IBD.

Laboratory Findings

• •Routine hematologic and biochemical parameters typically are unremarkable except for occasional non-specific findings such as a stress leukogram, hypoproteinemia, hypokalemia, and mildly elevated serum liver enzymes. Basenji enteropathy is associated with hypoalbuminemia and hyperglobulinemia, whereas affected soft-coated wheaten terriers may have hypoalbuminemia with concurrent protein-losing glomerulonephropathy. Cats with IBD may have concurrent cholangitis, pancreatitis, or both.
• •Serum vitamin levels (cobalamin, folate, vitamin K) can be decreased from malabsorption. Bleeding and abnormal hemostasis have been associated with vitamin K deficiency in some cats with IBD. Markedly decreased serum cobalamin is common, especially in cats and Shar-Peis with IBD.

Radiography and Ultrasonography

In most cases, radiographic and ultrasonographic findings are unremarkable and do not aid diagnosis. Some animals have a nonspecific finding of fluid- and gas-distended bowel loops on plain abdominal radiography. Barium contrast radiography occasionally demonstrates diffuse mucosal irregularity and ultrasonography may reveal intestinal thickening, but these are nonspecific findings that merely suggest an infiltrative lesion. In selected cases, contrast radiography and ultrasonography can be helpful nonetheless, because they may discover an unexpected diagnosis other than IBD—for example, pancreatitis, hepatobiliary disease, or intestinal tumors, polyps, granulomas, or malformations (e.g., diverticulum or short colon).

Endoscopic Examination

In animals with GI disease, the spectrum of clinical signs usually suggests the most appropriate region of the GI tract for endoscopic examination. In IBD, however, signs do not always correlate with the region of greatest cellular infiltration, especially in cats. It is not uncommon to find significant involvement of the colon in cats that present with vomiting. Conversely, cats with hematochezia or other colonic signs may have unexpected gastroduodenal lesions. Therefore, it may be advisable in many cases to obtain biopsies from the stomach, duodenum, jejunum (if possible), colon, and ileum (if the ileocolic sphincter can be navigated during colonoscopy).

Endoscopically, the mucosa in IBD may appear to be normal or it may have any of the following abnormalities: erythema, petechiae, increased mucus, increased friability, increased surface granularity, decreased visibility of the colonic submucosal vessels, thickened or increased folds, erosions or ulcers, or decreased distensibility. The mucosal lesions may only be apparent microscopically; thus, a normal endoscopic appearance does not rule out IBD and multiple biopsies should be taken even if there are no endoscopically visible abnormalities.

Mucosal Histopathology

The histopathologic lesion of lymphocytic-plasmacytic IBD is characterized by diffuse infiltration of the lamina propria with mature lymphocytes and plasma cells in association with mucosal damage. For definitive diagnosis of lymphocytic-plasmacytic IBD, there must be abnormal infiltration of lymphocytes and plasma cells, as well as evidence of mucosal damage.

• •Pathologists may differ in their interpretation of endoscopic biopsies and in their definition of how many lymphocytes and plasma cells within the lamina propria are too many. Infiltrates assessed to be minimal or mild by an inexperienced pathologist may not be truly abnormal. Various grading systems have been proposed, but these have not correlated well with clinical disease activity.
• •In some cases the inflammation is mostly lymphocytic; in others the infiltrate also contains a mixture of other types of inflammatory cells (neutrophils, eosinophils, macrophages). The cellular infiltrate is usually confined to the mucosa but occasionally may extend to the submucosa.
• •Additional findings indicative of mucosal damage include architectural distortion (e.g., atrophic or fused villi), fibrosis, and epithelial abnormalities (hyperplasia, degeneration, necrosis, erosion, ulceration, glandular dilation, loss of goblet cells).
• •A severe infiltration of lymphocytes that extends beyond the mucosa into the submucosa and muscularis should raise the suspicion of early lymphoma mimicking IBD, and further diagnostics should be recommended.

Evaluation for Dietary Hypersensitivity

Dietary hypersensitivity or food allergy is an immunologically mediated adverse reaction to a protein component in food. A well-controlled dietary trial using a protein elimination diet is the basis for diagnosis of dietary hypersensitivity as a cause of IBD (for additional information on diagnostic food trials, see Chapter 47). The diet is changed to a well-defined, additive-free, highly digestible diet that contains a single source of protein not found in the animal's normal diet. Intake of all other foods or sources of antigen must be eliminated throughout the feeding trial, including table scraps, treats, and flavored medications such as vitamin supplements. The goal is to feed a single protein source to which the animal is not yet sensitized. Although many commercial hypoallergenic diets are available (see the next section), home-prepared single-protein diets are preferred for diagnostic testing purposes. Examples of novel protein sources not likely found in the animal's regular diet might include turkey, duck, lamb, rabbit, venison, fish, or soybeans (tofu). Once dietary hypersensitivity is confirmed with a home-prepared diet, commercial hypoallergenic diets can be substituted for more convenient long-term management.

A cooperative and patient owner is required for a successful elimination diet trial. A minimum of 3 to 4 weeks should be allowed for initial response to an elimination diet. If no improvement has occurred during this time, then dietary hypersensitivity is unlikely and medical therapy should be instituted. If some improvement has been observed, then the trial should continue as it may require 6 weeks or more before improvement is complete.

If there is a substantial improvement with the elimination diet, then the animal can be rechallenged with its original diet. Recurrence of clinical signs confirms dietary intolerance or hypersensitivity. In addition, once remission is restored with the controlled diet, the animal can then be challenged sequentially with individual dietary components to identify the specific offenders. To do this, individual components of the original diet are added one at a time to the controlled diet while the animal is in remission. With each challenge the animal is monitored for recurrence of signs for 7 to 10 days. If signs recur, then that substance is implicated as an offender.

After several weeks to months of remission on the controlled diet, some animals can be returned to their original diet and remain asymptomatic, but in most cases, specially formulated or novel protein diets may need to be continued indefinitely to prevent relapse. If there is no response to dietary management within 4 to 6 weeks, the animal can be fed a digestible commercial GI diet or returned to its original diet and medical therapy can be instituted.

Treatment

Well-controlled therapeutic trials for chronic IBD in animals are lacking; thus, treatment is largely empirical and based on clinical experience. Because dietary hypersensitivity, parasites (see previous section), and bacterial enteropathogens (see previous section) may cause lymphocytic-plasmacytic IBD, it is appropriate to first consider evaluation and treatment for these possibilities.

In most cases of lymphocytic-plasmacytic IBD, an underlying cause cannot be identified and the most effective treatment is an anti-inflammatory regimen of either corticosteroids or mesalamine (5-ASA derivative) combined with dietary modification (e.g., novel protein diet, hydrolyzed diet, or fiber-enriched diet). If diet and anti-inflammatory drugs fail to control the disease, metronidazole is added for its antibacterial and immunomodulatory properties. Metronidazole can also be used as a single drug to induce or maintain remission in less severe cases. For refractory cases, a cytotoxic immunosuppressive agent such as azathioprine or chlorambucil can be added to the corticosteroid regimen. Cyclosporine may also be beneficial in steroid-refractory cases. Various drugs used to treat IBD and their suggested dosages are indicated in Table 69-7 .

Table 69-7.

TREATMENT OF INFLAMMATORY BOWEL DISEASE

Drug	Product (Manufacturer)	Preparations	Dosage
Anti-inflammatory Drugs/Immunosuppressives
Prednisone*	Many	Tab: 5, 10, 20, 50 mg	Dog: 1–2 mg/kg PO q24h
			Cat: 2–3 mg/kg PO q24h
Budesonide	Entocort (AstraZeneca)	Cap: 3 mg	Dog: 1–3 mg PO q24h
			Cat: 1 mg PO q24h
Methylprednisolone acetate	Depo-Medrol (Upjohn)	Inj: 40 mg/ml	Cat: 20 mg IM q2–4wk
Azathioprine†	Imuran; Azasan (Salix)	Tab: 25, 50, 75 mg	Dog: 1–2 mg/kg PO q24–48h
			Cat: 0.3–0.5 mg/kg PO q24–48h
Chlorambucil	Leukeran (Glaxo)	Tab: 2 mg	0.1–0.2 mg/kg PO q24–48h, or 2–3 mg/m2 PO q24–48h, or 15–20 mg/m2 PO once every 3 weeks (cats)
Cyclosporine	Atopica (Novartis)	Cap: 10, 25, 50, 100 mg	5 mg/kg PO q24h
Colonic Anti-inflammatory Drugs
Sulfasalazine‡	Generic	Tab: 500 mg	Dog: 10–30 mg/kg PO q8–12h
			Cat: 10–20 mg/kg PO q12–24h
Olsalazine	Dipentum (Celltech)	Cap: 250 mg	Dog: 10–20 mg/kg PO q12h
Mesalamine	Asacol (Procter & Gamble)	Tab: 400 mg	Dog: 10–20 mg/kg PO q8–12h
	Pentasa (Shire)	Tab: 250 mg
Anti-inflammatory Retention Enemas§
5-Aminosalicylate	Rowasa (Solvay)	Enema: 4 g/60 ml	To be determined
Hydrocortisone	Cortenema (Reid-Rowell)	Enema: 100 mg/60 ml	20–60 ml rectally q24h
Antibiotics
Metronidazole	Flagyl (Searle) or generic	Tab: 250 mg, 500 mg	10–20 mg/kg PO q8–12h
Tylosin tartrate¶	Tylan Soluble (Elanco)	Powder: 2270 mg/tsp	Dog: 20–40 mg/kg PO q12h
			Cat: 10–20 mg/kg PO q12h
Opioid Motility/Secretory Modifier
Loperamide	Imodium AD	Tab: 2 mg	Dog: 0.1–0.2 mg/kg PO q8–12h
		Liq: 0.2 mg/ml	Cat: 0.1–0.3 mg/kg PO q12–24h
Adjunct Therapy
Cobalamin	Generic	Inj: 1000 mg/ml	Dog: 250–1000 mg weekly
			Cat: 250 mg weekly
Psyllium	Metamucil (Procter & Gamble)	Powder	Dog: 1–3tbsp/day with food
			Cat: 1–3tsp/day with food

^*In some cats with severe colitis, prednisone dosage may need to be increased to 5 mg/kg/day, divided bid. In dogs, if steroidal side effects become a problem, decrease dosage and combine with azathioprine, metronidazole, or both.

^†May cause myelotoxicity, so monitor the complete blood count; formulate as an oral suspension for accurate dosing of cats.

^‡Dosage may need to be increased to 25–50 mg/kg q8h to achieve effect in some dogs; may cause keratoconjunctivitis sicca in dogs and salicylate toxicosis in cats.

^§Retention enemas for topical therapy of the distal colon may relieve signs of tenesmus and urgency in some animals with proctitis.

^¶Tylan Soluble can be mixed with dextrose or cornstarch. Tylosin powder is bitter-tasting and thus best tolerated when mixed with food. Cap, capsules; Inj, injectable; Liq, elixir, suspension, or drops; Tab, tablets.

Dietary Therapy

Various strategies for dietary modification have been used for treatment of chronic IBD, including novel protein diets, hydrolyzed diets, fiber-enriched diets, diets with adjusted omega-6 and omega-3 fatty acid levels and diets with prebiotics and probiotics. In some animals with IBD, dietary modification produces complete or partial resolution of the signs and sometimes regression of the lesions. Potential explanations for a beneficial response to dietary modification include the effects of the diet on bowel motility, composition of the microflora, mucosal morphology and function, and exposure to food-borne antigens or additives.

• •The treatment of IBD associated with dietary hypersensitivity is based on the controlled feeding of a well-defined, additive-free, highly digestible diet that contains a single source of protein not found in the animal's normal diet (i.e., a novel protein to which the animal is not yet sensitized). Home-prepared diets (turkey, duck, lamb, rabbit, venison, white fish, or tofu) are most suitable for diagnostic testing purposes (see previous “Diagnosis” section); however, if the home-prepared diet suggests diet-responsive disease, then a commercial “hypoallergenic” novel protein diet can be substituted and is more convenient and balanced for long-term feeding. Many commercial diets that contain novel protein sources are now marketed for dietary hypersensitivity. A relapse rate of approximately 15% to 20% is to be expected when switching from a home-prepared to a commercial hypoallergenic diet. For long-term feeding of a home-prepared diet, recipes for balanced diets containing novel protein sources can found in veterinary nutrition text books or various reliable websites under supervision of Diplomates of the American College of Veterinary Nutrition.
• •An alternative approach is to use a diet containing hydrolyzed proteins (oligopeptides) that may be less antigenic (e.g., Prescription Diet z/d, Hills; or HA Diet, Purina).
• •In cases in which hypoallergenic novel protein diets have not been effective, other dietary adjustments may be beneficial as an adjunct to medical therapy for IBD. This includes fiber supplementation (psyllium, bran, canned pumpkin) of the regular diet or switching to a commercial diet enriched with fermentable fiber (e.g., beet pulp) marketed for improving colonic function and ameliorating diarrhea in animals with colitis. Fiber has many beneficial effects on colonic function and helps keep enteropathogens in check. Colonic bacteria metabolize fermentable fiber to short-chain fatty acids that nourish colonic epithelium and protect against mucosal injury.
• •Modification of the intestinal bacterial flora is the aim of probiotics (orally administered live bacterial cultures such as Lactobacillus) and prebiotics (beneficial dietary carbohydrate substrates such as lactulose and fructo-oligo-saccharides).
• •Adjustment of the levels of omega-6 and omega-3 fatty acids in the diet has been proposed to manage bowel inflammation through decreasing inflammatory mediators, although evidence for this is lacking.

Cobalamin Therapy

Cobalamin (vitamin B₁₂) is frequently depleted in patients with chronic IBD, especially cats, and cobalamin deficiency can impair intestinal mucosal regeneration and cause mucosal atrophy, exacerbat-ing diarrhea and making the patient refractory to the usual anti-inflammatory therapy. Thus, evaluate serum cobalamin and treat with parenteral cobalamin (1000μg/ml) when serum levels are decreased, especially if <100 ng/L. Give injections weekly for at least 6 weeks, then every other week for 6 weeks, and then monthly.

• •For cats and small dogs: Give 250μg SC, weekly
• •For medium dogs: Give 500μg SC, weekly
• •For large dogs: Give up to 1000μg SC, weekly

Corticosteroids

Oral prednisone or prednisolone is the most consistently effective medical therapy (1-2 mg/kg/day for dogs and 2-4 mg/kg/day or a 5-mg total dose q12h for cats) for initial treatment of lymphocytic-plasmacytic IBD. Clinical improvement using this dosage should be noted within 1 to 2 weeks. After 2 weeks of remission, the dosage is tapered in 2- to 4-week increments to the lowest effective alternate-day dosage.

• •In some cases dexamethasone seems to be more effective than prednisolone with fewer side effects.
• •In cats that are too difficult to medicate orally, periodic injections of methylprednisolone acetate (20 mg IM or SC q2-4wk) may be substituted for oral treatment.
• •Budesonide (0.5-1-mg total dose/cat and 0.5-3-mg total dose/dog, PO q24-48h) is an alternative corticosteroid for refractory cases. Budesonide has high receptor-binding affinity in the mucosa and undergoes extensive first-pass metabolism in the liver. It achieves particularly high mucosal anti-inflammatory activity with less systemic side effects. It may be cost prohibitive for some owners.
• •Corticosteroid therapy may be discontinued on a trial basis after 6 to 12 weeks of remission; however, continuous alternate-day therapy is often required to prevent relapse.
• •In refractory cases, metronidazole or mesalamine (see the next sections) should be added to the prednisolone regimen. If this fails to control the disease, then the combination of azathioprine in dogs or chlorambucil in cats (see a later section) with prednisolone may be more effective for achieving remission of the disease.

5-Aminosalicylic Acid (Mesalamine)

These drugs exert an anti-inflammatory effect targeted at the colon through local inhibition of mucosal leukotrienes and prostaglandins. In dogs with IBD, 5-ASA drugs are the initial drugs of choice when the colon alone is involved. Orally administered 5-ASA derivatives are designed to be minimally absorbed during passage through the small intestine so that they reach the colon. These drugs should be used cautiously in cats as some salicylate absorption occurs and cats metabolize salicylates very slowly.

Sulfasalazine

In this drug, 5-ASA is combined with sulfapyridine by an azo bond that prevents significant absorption of the drug so that 75% of it reaches the colon, where bacteria split the bond and release the 5-ASA for its local effect in the colon (see Table 69-7 for dosages).

• •The most common adverse side effect of sulfasalazine is keratoconjunctivitis sicca. When it occurs, the decline in tear production is often irreversible. For this reason, it is recommended that a baseline Schirmer tear test be performed at the start of therapy and monitored subsequently at monthly intervals if treatment is long term.
• •Less common side effects include allergic dermatitis, nausea and vomiting, and cholestatic jaundice. Rarely, cats may develop anemia.
• •Because up to 30% of the salicylate is absorbed and cats metabolize salicylates very slowly, use caution when treating cats with this drug to avoid salicylate toxicity.

Olsalazine (Dipentum)

This newer derivative, consisting of two molecules of azo-bonded 5-ASA, is poorly absorbed so that more than 90% reaches the colon, where the two 5-ASA molecules are then released by the action of colonic bacteria on the azo bond (see Table 69-7 for dosages).

• •The advantages of olsalazine over sulfasalazine are that olsalazine contains only 5-ASA (without sulfa) so that side effects are fewer and that a greater percentage of the drug reaches the colon.
• •Unfortunately, olsalazine is currently available only in 250-mg capsules, an inconvenient size for dosing most animals.

Polymer-Coated Mesalamine (Asacol)

A pH-sensitive coating prevents release of 5-ASA until the drug reaches the site of inflammation in the colon.

Pentasa

Encapsulation prevents release of 5-ASA until the drug reaches the site of inflammation in the colon.

Mesalamine Suspension Enema

This form of 5-ASA (Rowasa, Reid-Rowell) is available for direct instillation into the rectum. In animals, enema administration of 5-ASA is probably not as effective as the oral route except when proctitis is the principal manifestation.

Metronidazole and Other Antibiotics

Low-dose metronidazole therapy (Flagyl at a dosage of 10-20 mg/kg q12h) is often beneficial either alone or in combination with prednisolone to treat IBD.

• •The beneficial effects of metronidazole in any animal with diarrhea might be attributable to an antibacterial effect on enteropathogens (e.g., enterotoxigenic C. perfringens), an antiprotozoal effect (e.g., Giardia), a reduction of bacterial-derived antigens that could be involved in the immunopathogenesis of IBD, or the immunomodulating effect of the drug on cell-mediated immunity and neutrophil chemotaxis.
• •Metronidazole tablets have an unpleasant taste and provoke salivation in most cats and sometimes vomiting. For ease of administration and accurate dosing, a liquid suspension can be formulated on request by many pharmacists or the tablets can be split and placed in gel capsules.
• •Dosages of metronidazole exceeding 50 mg/kg/day for prolonged periods (weeks) occasionally cause signs of reversible CNS toxicity (ataxia, weakness, seizures).
• •Other antibiotics that might be helpful to control intestinal microflora include tylosin (Tylan) or doxycycline (see Table 69-7).

Azathioprine and Chlorambucil

• •In IBD patients refractory to 5-ASA drugs, prednisone, and metronidazole, the combination of azathioprine (Imuran) or chlorambucil (Leukeran) with prednisone may be a more effective immunosuppressive regimen for producing remission of the disease (see Table 69-7). Besides treating refractory IBD, the addition of azathioprine enables use of a lower dose of corticosteroid to control the disease and thereby minimizes steroidal side effects.
• •Azathioprine usually is given as a daily treatment until remission occurs and then decreased to an alternate-day treatment (alternating with every-other-day prednisone) for maintenance. Because of its myelosuppressive toxicity (leukopenia), periodically monitor the CBC of azathioprine-treated animals, especially in the first 2 months, and use lower dosages in cats (see Table 69-7). In cats, formulate azathioprine as an oral suspension to facilitate accurate and safe dosing.
• •Chlorambucil (0.1-0.2 mg/kg PO, or 2.0 mg/m² PO, q24-48h; alternatively, 15-20 mg/m² PO, once every 3 weeks) is an effective alternative to azathioprine that is well tolerated by most cats.

Cyclosporine

Cyclosporine (Atopica, Novartis) (5 mg/kg PO q24h) is useful for treating corticosteroid-refractory IBD. Cyclosporine is a potent immunosuppressive drug that inhibits interleukin-2 and T cell recruitment. Transient anorexia and vomiting are common side effects at the start of treatment but these resolve within 2 weeks.

Motility-Modifying Antidiarrheal Drugs

Adjunctive use of motility-modifying drugs may provide some symptomatic relief for animals with IBD (see Table 69-5 for dosages).

• •Opioid drugs such as loperamide (Imodium) and diphenoxylate (Lomotil) may aid control of diarrhea by acting on intestinal smooth muscle to inhibit propulsive movements and by inhibiting mucosal efflux of water and electrolytes.
• •Anticholinergic antispasmodics such as dicyclomine (Bentyl) may be beneficial in colitis patients with severe tenesmus and urgency associated with rectocolonic spasm.

Prognosis

• •Monitor clinical response using a canine IBD activity index and sequential evaluation of C-reactive protein as a serum marker of inflammation.
• •Inform the owner that persistence or recurrence of IBD is likely despite therapy; thus, a realistic expectation is the maintenance of remission or control of relapses rather than a permanent cure.
• •The clinical course in basenjis, soft-coated wheaten terriers, and Shar-Peis is often progressive despite treatment.

Eosinophilic Gastroenteritis

Eosinophilic gastroenteritis (EGE) is a relatively uncommon form of IBD that is characterized by diffuse or segmental infiltration of some portion of the GI tract with mature eosinophils, often accompanied by a peripheral eosinophilia.

Etiology

Food allergy and parasitism (e.g., visceral larva migrans) have been proposed as causes, but in most patients evidence for these is lacking and the disease must be considered idiopathic.

Clinical Signs

• •One or more layers of the stomach, small intestine, or colon may be affected, resulting in clinical syndromes of chronic vomiting (eosinophilic gastritis) (see Chapter 67), chronic small bowel-type diarrhea (eosinophilic enteritis), chronic large bowel-type diarrhea (eosinophilic colitis), or any combination of these. Weight loss is frequent.
• •Diffuse infiltration of the intestinal tract with eosinophils may result in malabsorption (watery diarrhea and weight loss) or protein-losing enteropathy.
• •Diarrhea or vomitus may contain blood from mucosal erosions or ulcers.
• •Eosinophilic granulomas of the deeper layers of the bowel wall occasionally produce segmental tumor-like thickenings that can cause partial intestinal obstruction.

Diagnosis

• •The history may indicate dramatic responsiveness to prior glucocorticoid therapy.
• •Palpation may reveal diffusely thickened intestinal loops or a tumor-like intestinal mass (eosinophilic granuloma).
• •Laboratory evaluation may reveal peripheral eosinophilia (although not present in all cases), hypoproteinemia, or impaired absorptive function tests.
• •Routine fecal flotation is indicated because parasitism can also cause eosinophilic inflammation; it is important to exclude occult whipworm or hookworm infection in dogs by response to a therapeutic trial of an anthelmintic such as fenbendazole (see Table 69-6).
• •Barium GI radiography and abdominal ultrasono-graphy may be normal, may indicate thickening and irregularity (mucosal filling defects) of bowel loops, or may delineate sites of partial luminal obstruction caused by eosinophilic granulomas.
• •The diagnosis is based on demonstration of eosinophilic inflammation in intestinal biopsies. The endoscopic appearance is similar to that described for lymphocytic-plasmacytic IBD except that mucosal ulceration is more common in EGE. Occasionally, lesions are deep in the submucosa and found only by full-thickness biopsy.

Treatment

• •Consider a trial of fenbendazole (Panacur), given at 50 mg/kg daily for 3 days, to rule out GI parasitism.
• •Because food allergy is a potential cause of EGE in some animals, a feeding trial using an elimination or novel protein diet (as described for lymphocytic-plasmacytic IBD) can be considered initially; however, dietary therapy alone is seldom effective.
• •Oral prednisone usually is the most effective treatment for EGE at an initial dosage of 1 to 2 mg/kg/day for dogs and 2 to 3 mg/kg/day for cats. Clinical signs typically improve rapidly, especially when infiltration is limited to the mucosa. When remission has been maintained for 2 weeks, gradually taper the dosage over an additional 2 to 4 weeks to the lowest effective maintenance dose.
• •In some animals the treatment can eventually be discontinued, but in others alternate-day maintenance therapy is required.
• •In some patients it may be necessary to add azathioprine to the corticosteroid regimen (as described for lymphocytic-plasmacytic IBD) to facilitate reduction of corticosteroid dosage and side effects or to provide more effective control of the disease.
• •Obstructing transmural eosinophilic granulomas involving a localized segment of bowel wall occasionally require surgical excision followed by corticosteroid therapy.

Feline Hypereosinophilic Syndrome

Feline hypereosinophilic syndrome, a rare disease of cats, is characterized by severe eosinophilic GI infiltration accompanied by widespread infiltration of various other organs (liver, spleen, lymph nodes, bone marrow, lung, pancreas, adrenals, skin).

Etiology

The aggressive course and high mortality associated with this syndrome are consistent with malignant neoplasia involving eosinophils (see Chapter 22); thus, it is very distinct from the benign EGE that is confined to the GI tract.

Clinical Signs

• •Vomiting, diarrhea (sometimes bloody), anorexia, and weight loss are the most consistent clinical signs.
• •Clinical deterioration is rapidly progressive and the disease is eventually fatal.

Diagnosis

• •Abdominal palpation may reveal intestinal thickening, hepatosplenomegaly, or mesenteric lymphadenopathy because of the disseminated visceral infiltration of eosinophils.
• •Persistent, severe eosinophilia is a consistent CBC finding in affected cats.
• •The diagnosis depends on histopathologic confirmation of tissue infiltration and effacement by eosinophils in biopsies of affected organs.

Treatment

• •Use high-dose prednisolone (4-6 mg/kg/day for 2-4 weeks) to induce remission, followed by half this dose for 2 to 4 weeks and then by 1 to 2 mg/kg daily or on alternate days for maintenance. Add chlorambucil (see Table 69-7) or other cancer chemotherapeutics in refractory patients.

Prognosis

Unlike EGE confined to the GI tract, feline hypereosinophilic syndrome has a poor prognosis despite treatment.

Regional Granulomatous Enterocolitis

Regional granulomatous enterocolitis (RGE) is an uncommon form of IBD characterized by transmural granulomatous inflammation that results in a stenosing, mass-like thickening of a region of the bowel wall. The ileocolic junction is most often involved, and the mass may incorporate adjacent lymph nodes and mesentery. In some dogs the granulomatous lesions also contain numerous eosinophils (eosinophilic granuloma).

Clinical Signs

The principal clinical sign of RGE is chronic large bowel diarrhea containing mucus and fresh blood, sometimes accompanied by tenesmus and abdominal pain. Additional signs may include weight loss, anorexia, and depression.

Diagnosis

• •The diseased segment of bowel may be palpable as a firm mass in the mid-abdomen. The adjacent intestinal loops and mesentery may also be thickened and regional lymph nodes may be enlarged.
• •A routine CBC may reveal eosinophilia, neutrophilia, or monocytosis. Panhypoproteinemia due to excessive enteric loss of protein may be found in some animals.
• •Barium contrast radiography of the ileum and colon may delineate a thickened or stenosed segment of bowel and ultrasonography may identify an intestinal mass.
• •Definitive diagnosis of RGE requires biopsy by colonoscopy or laparotomy. The key feature is transmural granulomatous inflammation. Fibrosis and aggregates of epithelioid cells, giant cells, and eosinophils often are found deep in the lesion. Deep ulceration is common.
• •Differentiate RGE from intestinal neoplasia and infectious causes of granulomatous bowel lesions, such as histoplasmosis (Chapter 20), pythiosis, and mycobacteriosis (Chapter 19). Examine granulomatous lesions by special stains to detect fungi and acid-fast organisms. In cats, feline immunodeficiency virus (Chapter 9) and feline infectious peritonitis (Chapter 10) occasionally are associated with pyogranulomatous IBD.

Treatment

• •Medical treatment of regional granulomatous colitis is based on the use of anti-inflammatory and immunosuppressive agents such as olsalazine or sulfasalazine, prednisone, azathioprine, and metronidazole, as described for treatment of lymphocytic-plasmacytic IBD (see Table 69-7).
• •If the degree of thickening and cicatrization of the affected segment of bowel produces severe stenosis and obliteration of the lumen, surgical excision of the lesion may be necessary, followed by medical therapy for 6 to 8 weeks or longer to prevent recurrence of the lesion at the surgical site. Always submit the excised lesion for histopathological evaluation.

Histiocytic Ulcerative Colitis

• •Histiocytic ulcerative colitis is a chronic idiopathic IBD of young boxer dogs characterized by infiltration of the lamina propria and submucosa of the colon by distinctive histiocytes engorged with deposits that stain positive with periodic acid-Schiff (PAS) stain.
• •In addition to boxers, there have been isolated case reports of histiocytic colitis in a cat and a French bulldog, but it is not known if this is the same disease that occurs in boxers.

Clinical Signs

• •Affected boxers generally develop severe, unresponsive, bloody-mucoid large bowel diarrhea before 2 years of age.
• •Severe weight loss and debilitation occur in dogs with long-standing disease.

Diagnosis

The diagnosis is based on the known breed predisposition and the presence of numerous PAS–positive histiocytes in a colonoscopic biopsy. A mixture of other types of inflammatory cells is also found in the lesion, and usually there is severe mucosal ulceration.

Treatment

• •The treatment of choice is enrofloxacin (Baytril at 5 mg/kg PO q12h) alone or in combination with metronidazole, based on evidence that bacteria play a pivotal role in this disease. The optimal duration of therapy is not known, but clinical signs are resolved in most dogs within 3 to 4 weeks of starting enrofloxacin, and recovery has persisted more than 3 years after stopping the antibiotic.
• •Anti-inflammatory and immunosuppressive therapy (e.g., olsalazine or sulfasalazine, prednisone, azathioprine, and metronidazole) in single-agent or combination regimens, as described for lymphocytic-plasmacytic colitis, generally only provides temporary palliation of the disease.
• •In general, these dogs seem to have less diarrhea on a highly digestible diet than on a high-fiber diet.

Neutrophilic (Suppurative) Enterocolitis

Etiology

• •Bacterial enterocolitis (see under “Bacterial Infections of the Intestines”)
• •Idiopathic (i.e., neutrophilic IBD in the absence of an identifiable infectious cause)

Clinical Signs

• •Large bowel diarrhea that can be either acute or chronic.

Diagnosis

• •Colonoscopic biopsy shows infiltration of predominantly neutrophils, with variable mucosal ulceration, necrosis, or crypt abscesses.
• •Diagnosis is based on tests to exclude bacterial enteropathogens (see under “Bacterial Infections of the Intestines”).

Treatment

Give antibiotics (e.g., enrofloxacin, trimethoprim-sulfa, or tylosin) or regimens consisting of sulfasalazine, metronidazole, or anti-inflammatory or immunosuppressive drugs, as described for lymphocytic-plasmacytic IBD (see Table 69-7).

FIBER RESPONSIVE DIARRHEA (IRRITABLE BOWEL SYNDROME)

Etiology

Fiber-responsive diarrhea is characterized by chronic, non-inflammatory, mucoid large bowel diarrhea. The condition has resemblances to irritable bowel syndrome (IBS) seen in people.

Clinical Signs

• •Signs associated with myoelectrical dysfunction in humans with IBS are alternating patterns of diarrhea, constipation, and abdominal cramping.
• •Evidence for the existence of IBS in animals is circumstantial, but psychomotor diarrhea due to colonic motility dysfunction or neurogenic hyperreactivity may be a consideration in animals that have intermittent mucoid diarrhea but lack evidence of organic disease.
• •Hematochezia is usually absent.
• •Large breeds, especially those used as working dogs (e.g., police dogs, Seeing Eye dogs, and sled dogs), and temperamental or excitable dogs seem to be predisposed.

Diagnosis

The diagnosis is based on the complete absence of abnormal findings on diagnostic evaluation, minimal abnormalities on colonoscopic biopsy, and remission of clinical signs in response to modification of diet, particularly supplementation of fiber.

• •By definition, IBS is a functional disorder. The diagnosis can be established only by normal colonoscopic biopsy and diligent exclusion of the other known causes of colonic disease, such as dietary, parasitic, infectious, and chronic colitis (IBD).
• •At colonoscopy, the colon may appear to be hypermotile or spastic. The mucosa appears normal except for increased intraluminal mucus and an erythematous response to insufflation.

Treatment

Dietary Modification

Supplement a digestible GI diet with added dietary fiber in the form of psyllium (Metamucil) (1-5 tbsp/meal). This is sufficient to produce remission in many cases. Fiber may normalize colonic myoelectrical function and have beneficial effects on fecal consistency, water content, and bulk. In addition, fermentable soluble fiber is fermented by colonic bacteria to short-chain fatty acids that provide an energy source for colonic epithelium, protect against mucosal injury, and acidify bowel contents, which may alter the bacterial flora.

Medical Therapy

• •If dietary fiber supplementation is unsuccessful, consider medication to alter motility such as opioid drugs such as loperamide (see Table 69-5 for dosages).
• •Consider amitriptylin (Elavil) at 1 to 2 mg/kg PO q12h.
• •Light sedation during stressful times may be beneficial in excessively nervous or excitable animals.

PROTEIN-LOSING ENTEROPATHY

GI loss accounts for approximately 40% of the normal daily turnover of plasma proteins. The term protein-losing enteropathy refers to a variety of intestinal diseases that are associated with hypoproteinemia caused by an accelerated loss of plasma proteins into the gut. Mechanisms of excessive enteric loss of protein include the following:

• •Impaired intestinal lymphatic drainage (e.g., lymphangiectasia) that results in extravasation of protein-rich lymph into the lumen
• •Disruption of the mucosal barrier (e.g., inflammation) that results in protein leakage from sites of exudation, bleeding, or increased permeability

Etiology

Severe protein-losing enteropathy occurs most frequently in association with chronic enteropathies, such as the following:

• •Idiopathic canine intestinal lymphangiectasia
• •Chronic inflammatory small bowel diseases (lymphocytic-plasmacytic enteritis, granulomatous enteritis, eosinophilic enteritis, immunoproliferative enteropathy of basenjis)
• •Intestinal histoplasmosis
• •Intestinal lymphoma

Intestinal Lymphangiectasia

Lymphangiectasia is a chronic protein-losing enteropathy in dogs, characterized by marked dilation and dysfunction of the intestinal lymphatic network. Impaired intestinal lymph drainage is presumably caused by obstruction to the normal lymphaticovenous flow. It leads to stasis of chyle within dilated lacteals and lymphatics of the bowel wall and mesentery. Overdistended lacteals release intestinal lymph into the gut lumen by rupture or extravasation, causing loss of the constituents of chyle, including plasma proteins, lymphocytes, and lipid (chylomicrons).

Clinical Signs

• •The presenting signs of lymphangiectasia usually are attributable to protein-losing enteropathy and include dependent pitting edema of subcutis and limbs, fluid distention of the abdomen (ascites), and respiratory distress (hydrothorax). These manifestations of fluid transudation are the result of hypoalbuminemia and reduced plasma colloidal osmotic pressure.
• •Chronic intermittent or persistent diarrhea with a watery or semisolid consistency often is observed, but not all patients have diarrhea.
• •Progressive weight loss is common. Clinical signs often develop insidiously.

Diagnosis

Key Point.

Typical laboratory findings in intesti-nal lymphangiectasia include hypoalbuminemia, hypoglobulinemia, lymphocytopenia, hypocholesterolemia, and hypocalcemia.

• •Differentiate protein-losing enteropathy from nonenteric causes of hypoproteinemia, such as liver failure (impaired hepatic synthesis of albumin) and renal disease (protein-losing glomerulonephropathy), through liver function testing (Chapter 71) and urine protein determinations (Chapter 77), respectively.
• •Radiography can detect or confirm ascites and pleural effusion.
• •Fluid analysis of body cavity effusions may be helpful. The effusion associated with lymphangiectasia is usually a transudate. Chylous ascites and chylothorax are found occasionally.
• •Cardiac evaluations can exclude right-sided congestive heart failure, which is a rare cause of lymphangiectasia.
• •Definitive diagnosis of lymphangiectasia is based on identification of the characteristic lymphatic lesions in biopsies obtained via laparotomy, or less invasively by endoscopy. Laparotomy may reveal the mesentery and serosa to have a prominent, weblike network of distended, milky-white lymphatics along with small, yellow-white nodules and foamy granular deposits (lipogranulomas) adjacent to lymphatics.

Treatment

The major goal in treating intestinal lymphangiectasia is to decrease the enteric loss of plasma proteins so that normal plasma protein levels can be restored and edema and effusions can be controlled. This is accomplished with dietary manipulation and anti-inflammatory therapy as described under “Inflammatory Bowel Disease.”

• •The plasma protein loss and diarrhea of lymphangiectasia often benefit from anti-inflammatory doses of corticosteroids (prednisone at a dosage 2-3 mg/kg/day PO). When remission has been achieved, adjust the dosage to the lowest effective maintenance level. The addition of metronidazole and azathioprine is helpful in some cases (see Table 69-7).
• •Because absorption of dietary long-chain triglycerides (LCTs) is a major stimulus of intestinal lymph flow, restriction of dietary intake of fat may reduce lymph flow, lymphatic distention, and protein loss in lymphangiectasia. Supplement diets with fat-soluble vitamins.

Prognosis

The prognosis and response to therapy is unpredictable. Many patients achieve remission of months to years with combined dietary and anti-inflammatory therapy. However, some animals fail to respond and many eventually relapse to finally succumb to severe protein-calorie depletion, incapacitating effusions, or intractable diarrhea.

VILLOUS ATROPHY

Etiology

Villous atrophy is a lesion of the small intestine characterized by short, blunted mucosal villi and is associated with intestinal malabsorption and chronic diarrhea. The forms of villous atrophy may be categorized as primary or secondary.

Primary Forms

• •Gluten-sensitive enteropathy of Irish setters resembles gluten enteropathy of humans (celiac disease, non-tropical sprue). This is inherited as an autosomal recessive trait, mostly in Irish setters in Great Britain and is characterized by partial villous atrophy, deficiency or delayed development of specific microvillus enzymes, and dietary sensitivity to wheat.
• •Idiopathic canine villous atrophy is recognized most often in German shepherds.

Secondary Forms

• •Sequelae of diffuse infiltrative diseases of the intestines, such as chronic IBD and lymphoma
• •Sequelae of enteric infections, such as viruses (coronavirus, rotavirus), bacteria (small intestinal bacterial overgrowth syndrome), and parasites (Giardia)

Clinical Signs

Villous atrophy generally causes chronic small bowel-type diarrhea and weight loss. The severity of signs depends on the degree of disruption of the villous absorptive surface area.

Diagnosis

Histologic examination usually is adequate for documentation of villous atrophy. However, because this can be a nonspecific secondary lesion found in various enteropathies, the diagnosis is mainly based on the following:

• •Breed predilection (German shepherds, Irish setters in Great Britain)
• •Response to withdrawal of wheat from the diet
• •Tests or procedures to identify enteric infections (e.g., Giardia) or bacterial overgrowth
• •Characterization of morphologic and biochemical abnormalities in jejunal biopsies

In some cases, infiltration of lymphocytes and plasma cells and fibrosis make it difficult to determine if the lesion should be categorized as a primary idiopathic villous atrophy or as chronic IBD (lymphocytic-plasmacytic enteritis) with secondary villous atrophy (see under “Lymphocytic-Plasmacytic Inflammatory Bowel Disease”).

Treatment

Gluten-Sensitive Enteropathy

In gluten-sensitive Irish setters, the signs and lesions of villous atrophy promptly resolve with complete elimination of wheat and other gluten-containing cereal grains (barley and rye) from the diet. Most commercial dog foods contain gluten; however, diets that are based on rice or corn rather than wheat or gluten-containing grains are commercially available. Wheat restriction must continue for life, and breeding of affected animals is discouraged.

Idiopathic Villous Atrophy

• •Dietary management with a gluten-restricted hypoallergenic diet (e.g., Hill's Prescription Diet d/d) is sometimes beneficial.
• •Vitamin therapy with folate (5 mg daily PO) and cobalamin (250-1000μg SC weekly for 6 weeks, then every 2-4 weeks, for 6 months) is indicated if serum levels of these are low.
• •Antibiotic therapy is sometimes beneficial, using antibiotics such as oxytetracycline, tylosin, or metronidazole to empirically treat bacterial overgrowth (see under “Small Intestinal Bacterial Overgrowth”).
• •Prednisone as used for treatment of IBD (1-3 mg/kg/day PO for 4 weeks, followed by tapering to lowest effective alternate-day dosage) may produce clinical improvement in dogs with idiopathic villous atrophy that fail to respond to dietary modification, vitamins, or antibiotics.

Prognosis

The prognosis is guarded, as diarrhea and weight loss often persist despite treatment.

SMALL INTESTINAL BACTERIAL OVERGROWTH

Bacterial overgrowth syndrome is an overproliferation of microflora within the proximal small intestine that results in malabsorption and diarrhea. Human criteria that define bacterial overgrowth as a fasting bacterial count in duodenal juice of greater than 10⁵ organisms per milliliter of intestinal contents do not appear to be valid in dogs and cats; thus, definitive evidence of this syndrome in animals is lacking. For this reason, some veterinary gastroenterologists prefer to call this syndrome antibiotic-responsive diarrhea.

Etiology

The normal small intestinal microflora is a stable population of aerobic and facultative anaerobic bacteria whose growth is regulated and influenced by a combination of host factors, bacterial interactions, and dietary composition. Mechanical self-cleansing action of normal intestinal motility and continuous downstream flow of ingesta are especially important for preventing bacterial overgrowth.

Because documentation of bacterial overgrowth is difficult, the syndrome may occur more frequently in dogs and cats than is generally recognized. Development of an abnormal small bowel flora should be considered a potential secondary complication in the following situations:

• •Intestinal surgery
• •Stasis-producing mechanical obstructions such as chronic intestinal foreign bodies and stenosing neoplastic or inflammatory lesions of the gut
• •Destructive lesions of the ileocecocolonic junction that allow colono-enteric reflux
• •Motility disorders such as idiopathic intestinal pseudo-obstruction
• •Immune deficiency states with lack of immunoglobulin A (proposed as the explanation for an apparent breed predilection for overgrowth in German shepherds, basenjis, and Shar-Peis)
• •Conditions associated with hyposecretion of gastric acid
• •Exocrine pancreatic insufficiency

Clinical Signs

• •Bacterial overgrowth typically causes chronic, foul-smelling watery diarrhea, steatorrhea, and weight loss; however, additional presenting clinical signs can depend somewhat on the underlying cause of the abnormal proliferation of flora.
• •Diarrhea caused by overgrowth usually does not contain blood or mucus.
• •Bacterial overgrowth may be responsible for failure of some dogs with exocrine pancreatic insufficiency to respond adequately to enzyme supplementation.

Diagnosis

Definitive diagnosis of small intestinal bacterial overgrowth requires quantitative aerobic and anaerobic cultures of duodenal juice. Duodenal culture specimens are taken by endoscopy, intestinal intubation, or laparotomy after an 18-hour fast. This is impractical for routine clinical application.

Indirect evidence of bacterial overgrowth in animals with unexplained small bowel diarrhea and malabsorption includes the following observations:

• •Responsiveness to antibiotics (e.g., tetracyclines, tylosin, or metronidazole)
• •Delayed intestinal transit of barium on radiographs (suggestive of obstruction or poor motility)
• •Idiopathic pseudo-obstruction manifested by a dilated, hypomotile segment of gut
• •Elevated serum folate and decreased serum cobalamin (because bacteria may synthesize folate and bind with or utilize cobalamin)
• • Minimal morphologic abnormalities in intestinal biopsies
• •Unlike many other enteropathies, mucosal morphology in bacterial overgrowth may be normal or characterized by mild atrophy of villi and minimal increase in mononuclear cells in the lamina propria
• •Failure to obtain the expected treatment response in other intestinal disorders known to be conducive to bacterial overgrowth (such as exocrine pancreatic insufficiency)

Treatment

• •Identify and treat underlying disorders or predisposing factors. In animals with stasis caused by anatomic abnormalities, this may include surgery.
• •
  Antibiotic therapy:

  • •
    Oral broad-spectrum antimicrobials and those with activity against anaerobes are recommended, such as tetracycline, oxytetracycline, doxycycline, metronidazole, ampicillin, chloramphenicol, tylosin, and erythromycin.
  • •
    Continue treatment for at least 10 to 14 days and repeat as necessary. Some animals need continuous treatment; others may remain in remission for months after one course of antibiotics.
  • •
    Clinical signs and abnormal function tests usually resolve within the first week of therapy, which in itself is good indirect evidence in support of the diagnosis.
• •Treatment with Lactobacillus or live yogurt culture usually is not effective for altering the enteric microflora.

INTESTINAL NEOPLASIA

Benign tumors of the intestinal tract include adenomatous polyps, adenomas, and leiomyomas. In dogs these occur most commonly in the rectum and terminal colon. The most common malignant neoplasms of the intestinal tract are adenocarcinoma and lymphoma. Less common malignancies include carcinoid tumors, leiomyosarcoma, fibrosarcoma, mastocytoma, hemangiosarcoma, and anaplastic sarcoma.

Etiology

Adenocarcinoma

• •Adenocarcinomas are locally invasive and slow growing and are usually seen in older animals. The most common sites in dogs are the duodenum and colon; in cats, the ileum and distal jejunum are the most common locations.
• •
  Morphologically there are three forms of adenocarcinoma:

  • •
    Infiltrative—Thickened stenotic region of the bowel that obstructs the lumen
  • •
    Ulcerative—Deep indurated mucosal ulcer with raised edges
  • •
    Proliferative—Lobulated expanding intestinal mass
• •Mucosal ulceration is frequent, sometimes resulting in melena and blood loss anemia.
• •Local invasion of the mesentery, omentum, and regional lymph nodes is common. More widespread metastasis also may occur.

Lymphoma

• •GI lymphoma arises from lymphocytes of the gut-associated lymphoid tissue (GALT) and is the most common extranodal lymphoma in dogs and cats (see Chapter 27).
• •In cats, intestinal lymphoma occurs mostly over 8 years of age and can be caused by feline leukemia virus (see Chapter 8), although as few as 30% are viremic.
• •
  Morphologically there are two types of intestinal lymphoma:

  • •
    Diffuse lymphoma—Diffuse infiltration of the lamina propria and submucosa with neoplastic lymphocytes, causing malabsorption and occasionally deep ulceration; this is difficult to distinguish from IBD
  • •
    Nodular lymphoma—Expanding intestinal mass, most often in the ileocecocolic region, causing progressive luminal obstruction
• •Metastasis to regional lymph nodes and other organs is common.

Clinical Signs

• •Small intestinal neoplasia typically develops insidiously with initial vague signs of anorexia and lethargy, progressing to diarrhea and intermittent vomiting. Weight loss develops and progresses in severity in parallel with tumor growth. Melena, hematemesis, anemia, fever, icterus, and abdominal effusion may also occur.
• •Colonic polyps and tumors cause hematochezia, dyschezia, and tenesmus, sometimes with mucoid diarrhea; thus, they are easily confused with inflammatory diseases of the colon and anorectal disease.
• •Multifocal GI lymphoma may invade the stomach, small intestine, or colon, in any combination, thereby varying the clinical presentation. Furthermore, signs of extraintestinal involvement of organs such as the liver, spleen, or kidney may add to the clinical signs and physical findings.

Diagnosis

• •Abdominal palpation often detects intestinal neoplasia as a firm midabdominal mass, thickened intestinal loops, or mesenteric lymphadenopathy.
• •Rectal palpation detects stenosing or polypoid rectal masses. Most adenomatous rectal polyps can be exposed at the anus by everting the rectal mucosa with gentle traction. Polyps usually appear dark red and lobulated, are extremely friable, and bleed easily.
• •Laboratory evaluation may reveal blood loss anemia, neutrophilic leukocytosis with left shift, hypoproteinemia, or elevated serum hepatic enzyme concentrations.
• •Radiography, particularly barium contrast, can be helpful for delineating regions of mucosal irregularity, luminal narrowing, and intramural infiltration, thickening, or nodularity. Thoracic radiography is indicated for detection of metastasis.
• •Abdominal ultrasonography may be used to detect and define intestinal mass lesions.
• •Surgical excision or biopsy of the affected segment of the bowel provides a definitive diagnosis.
• •Gastric, duodenal, or colonic lesions are accessible to endoscopic biopsy.
• •Percutaneous fine-needle aspiration can be used to make a cytologic diagnosis in selected cases in which the neoplastic intestinal mass or loop can be well delineated by palpation or ultrasonography.

Treatment

• •Surgical resection is the treatment of choice for benign tumors such as polyps and, when feasible, for adenocarcinomas and other non-lymphomatous tumors. Unfortunately, many malignant tumors of the intestinal tract are too advanced for successful resection by the time they are recognized clinically. Always submit excised tissue for thorough histopathologic examination, including evaluation of surgical margins.
• •Intestinal lymphoma can be treated with anticancer chemotherapy (see Chapters 26 and 27). Long-term remissions are possible in cats with low-grade or lymphocytic (“small cell”) lymphoma of the small intestine.
• •Treatment strategy and prognosis may be affected by complications such as malabsorption, protein-losing enteropathy, intestinal blood loss anemia, intestinal obstruction, intussusception, intestinal perforation and peritonitis, and metastasis to the liver or kidneys.

INTESTINAL OBSTRUCTION

Etiology

Intestinal obstruction in dogs and cats may be caused by intraluminal objects, intramural thickening or stenosis, and extramural compression. Specific causes include the following:

• •Foreign bodies (e.g., bones, toys, cloth, metallic objects, stones, peach pits, acorns, rubber nipples, rubber balls, and linear objects such as string and thread)
• •Intussusception
• •Intestinal volvulus
• •Intestinal torsion
• •Incarceration of bowel in a hernia (includes abdominal hernias of all types, diaphragmatic hernia, and internal herniation of gut loops through a tear in the mesentery)
• •Adhesions or stricture (post-trauma or post-surgery)
• •Intramural abscess, granuloma, or hematoma
• •Congenital malformation (stenosis or atresia)
• •Intestinal neoplasia

Pathophysiology

Proximal versus Distal Obstruction

The more proximal and complete the obstruction, the more acute and severe the signs and the greater the likelihood of dehydration, electrolyte imbalance, and shock.

• • Proximal obstructions cause gastric outlet occlusion, leading to persistent vomiting, loss of gastric secretions (hydrochloric acid), and metabolic alkalosis.
• • Distal obstructions cause varying degrees of metabolic acidosis. Distal and incomplete obstructions can be insidious, with vague, intermittent signs of chronic anorexia and occasional vomiting that span several days or even weeks, leading to progressive starvation.

Simple versus Strangulated Obstruction

Vascular compromise of the obstructed bowel worsens the severity of the condition.

• • Simple obstructions occlude the lumen without compromising vascular integrity.
• • Strangulated obstructions cause vascular compromise of the obstructed bowel segment. This occurs most often with intussusception, volvulus, and incarcerated hernia. The sequence of events following strangulation are edema and engorgement of the affected loop, tissue hypoxia and infarction of the bowel wall, accumulation of gut bacteria and toxins in the peritoneal fluid, and rapidly progressive toxemia and shock, culminating in death.

Clinical Signs

The clinical manifestations and consequences of obstruction depend on its location, completeness, and duration, as well as the vascular integrity of the affected bowel segment.

• •Acute onset of vomiting, anorexia, and depression are the most consistent clinical signs.
• •Other signs may include abdominal distention, diarrhea (watery, hemorrhagic, or melenic), abdominal pain (restlessness, panting, or abnormal body posture), and shock (acute collapse).

Diagnosis

• •Abdominal palpation may identify intestinal foreign bodies, intussusceptions (“sausage loop”), or gas- and fluid-distended loops of bowel proximal to the obstruction.
• •Radiography often confirms the presence of obstruction and delineates the cause, especially when contrast studies are used.
• •Radiographic findings suggesting obstruction include gas or fluid distention (mechanical ileus) of the bowel, delayed transit of contrast material, fixation or displacement of gut loops, luminal filling defects, and foreign objects within the lumen.
• •Cats commonly ingest radiolucent linear intestinal foreign bodies (e.g., thread, string, cloth, fishing line, dental floss, and decorative tinsel) that cause aggregation and plication of the bowel and have a distinctive radiographic pattern.
• •Laboratory findings often reflect fluid, electrolyte, and acid-base derangements; these vary with location, completeness, and duration of obstruction.
• •Leukocytosis with a left shift or degenerative leukopenia accompanied by septic abdominal effusion indicates intestinal ischemia or perforation with peritonitis (see Chapter 76).

Treatment

• •Intestinal obstructions are treated surgically. Give close attention to supportive care, especially maintenance of fluid, electrolyte, and acid-base homeostasis before, during, and after surgery (for further information on intestinal surgery, see Chapter 70).
• •Treatment includes management of complications such as necrosis or perforation of the bowel, peritonitis (see Chapter 76), and septic shock (see Chapter 156).