Diagnostic approach to diarrhea (Proceedings)

Diarrhea is one of the most common clinical signs of intestinal disease in companion animals and sometimes one of the most frustrating conditions for veterinarians to diagnose and successfully manage. It is best, and easiest, if the clinician has a logical, systematic approach to work up dogs and cats with diarrhea and be able to arrive at an accurate diagnosis. One should be able to wade through the myriad of available tests and be able to recognize the benefits and limitations of each.

Clues obtained during the history and physical exam will in most cases help to order your rule-out list. Clinicians cannot overlook this basic, simple step. Signalment is important as breed predilections for diarrheal disease can help order your rule-out list. For example a four-month-old febrile, unvaccinated Pitt Bull with small intestinal diarrhea will probably have a different rule-out list compared to a four-year-old Yorkshire terrier with small intestinal diarrhea.

With the economic climate and pressure today clinicians are often rushed during appointments. Despite the importance of a detailed history, important pieces of important information are often overlooked. A comprehensive history is essential to the diagnosis. The dietary history should include the diet being fed, measured meal size, meal time/s, recent and past diet changes, supplements and medications, and the possibility of dietary indiscretion. Dietary indiscretion can be a recent purposeful diet change, non-purposeful diet change, diet additive, new treats or table scraps, free-roaming behavior, possible foreign body ingestion, possible garbage ingestion, and exposure to toxins.

It is also important to describe and characterize the duration, frequency (continuous or intermittent), and appearance of the diarrhea. Is there mucus, hematochezia, melena, tenesmus or fecal incontinence? Has the fecal volume increased? Is the animal's appetite the same, increased or decreased? Has the animal lost weight and if so how much? Ask the owner if there are any inciting factors that trigger the diarrhea. Examples would include: other animals in the house, stress, travel, new household members, visitors, thunderstorms, loss of a pet or household member or a move. Does vomiting accompany the diarrhea? Does anything else accompany the diarrhea? The above answers to characterize the diarrhea will direct the diagnostic and treatment plan. To save time but ensure a thorough history is obtained develop your own gastrointestinal questionnaire. The client can answer while waiting or during the physical examination.

Based on your thorough history you should be able to determine if the diarrhea is small bowel, large bowel or mixed bowel in origin.

Small bowel diarrhea is characterized by weight loss, a mildly increased frequency of defecation and a large amount of feces produced per defecation. Patients with large bowel diarrhea do not lose weight but have an increased defecation frequency but less feces produced per defecation. Excess mucus, hematochezia and tenesmus are often seen. Accordingly, mixed bowel diarrhea has elements of small and large bowel diarrhea. This initial analysis is very important to guide the diagnostic and treatment plans.

The physical exam should begin as the patient walks into the examination room. The physical examination should detect fever, dehydration, weakness, lethargy, cachexia, pallor, tachycardia or bradycardia, effusion or edema. Particular attention should be paid to intestinal loop palpation to discern thickening, masses, distension or pain. A thorough rectal examination may reveal thickening of the rectum, sublumbar lymphadenopathy or masses.

Diagnostic testing is the next step in the work-up. Routine complete blood count, biochemical profile and urinalysis are often unremarkable but can yield clues to the cause of diarrhea. Panhypoproteinemia (low serum albumin and globulin) can indicate protein-losing enteropathy (PLE). PLE's are part of a syndrome with loss of serum proteins across an impaired intestinal mucosa. Before the administration of intravenous fluids the BUN (and creatinine) should be evaluated. An abnormal BUN: creatinine ratio is seen secondary to dehydration, high protein diet, gastrointestinal bleeding, or cachexia. Liver enzyme elevation should be cautiously interpreted because bacteria drain via the portal circulation and cause reactive elevation of hepatocellular leakage enzymes. Hypocholesterolemia can be seen with PLE's, secondary to decreased hepatic production, or with hypoadrenocorticism. This is especially important to remember because a glucocorticoid deficient Addisonian will have normal electrolytes but be lethargic and have concurrent gastrointestinal signs. Anemia may reflect blood loss into the gastrointestinal tract. It may be regenerative but become non-regenerative as iron deficiency develops or due to chronic disease. Eosinophilia may reflect presence of inflammatory bowel disease or gastrointestinal parasites. Cat may be FeLV/FIV positive. Serum thyroxine levels may be elevated in older cats with hyperthyroidism and chronic small intestinal diarrhea.

The fecal examination for parasites is an integral part of the evaluation of dogs and cats with chronic diarrhea. Fecal floatation is best performed on fresh feces less than one hour old but can be refrigerated for up to four days. Standing fecal floatation is widely used in veterinary practice due to its ease and expense; however, flotation with centrifugation is considerably more effective. With either method the meniscus should be properly transferred via the cover slip. The solution must have a specific gravity high enough to float most common parasite ova but low enough to avoid distortion of protozoal cysts. Zinc sulfate is the most commonly used solution.

Fecal smears stained with Wright's stain are easily performed but recently their efficacy has been challenged. Initially used to identify spiral-shaped bacteria, white blood cells, and fecal endospores (safety pins) associated with Clostridium perfringens, the yield is low. Spiral-shaped bacteria and a few fecal endospore/HPF are commonly found in fecal smears from healthy dogs and dogs with diarrhea. Even though the bacteria are likely representative of a Campylobacter-like (gull shaped) organism, there are many non-pathogenic species of Campylobacter and therefore not diagnostic. Peer-reviewed journals document the lack of correlation between the presence of the endospores and the presence or absence of diarrhea as well as between the endospore count and enterotoxin results.

Rectal scrapings and cytology are simple, inexpensive, non-invasive and are usually high yield in dogs suspected of having eosinophilic colitis and proctitis, Histoplasma (inclusions within macrophages), protothecosis, and colonic or rectal neoplasia (lymphoma or carcinoma).

Direct saline fecal wet smears can identify Giardia trophozoites, Campylobacter, Tritrichomonas foetus and Pentatrichomonas hominis. Use warm, fresh feces as older, cold samples of trophozoites lose their motility and deteriorate becoming unrecognizable. Low parasite burdens result in false negative results however it can detect about 20% of dogs with Giardia infections. Using successive stool samples increases the yield.

Giardia infection in dogs and cats are often subclinical however acute diarrhea is possible, which is often pale, covered with mucus and malodorous. Microscopic diagnosis is problematic as their delicate cysts only shed sporadically and artifacts cause many false positives. Currently a novel SNAP® ELISA Giardia test kit (IDEXX Laboratories) for detection of Giardia cyst wall protein I (GCWP 1) is in use. This is easy to perform, interpret and detects GCWP 1 even in the absence of detectable cysts. It can be used on fresh, refrigerated or frozen feces. This test is sensitive and highly specific although sensitivity increased with centrifugation flotation.

Cryptosporidium spp. infection of the young or immunocompromised can be asymptomatic to full-blown, life-threatening diarrhea. The author's lab also uses the Remel Xpect ELISA combo kit for Giardia and Cryptosporidium identification with good sensitivity and specificity.

Cobalamin (vitamin B12) is absorbed in the distal small intestine; especially the ileum therefore low serum cobalamin levels are seen in patients with distal small intestinal disease and or exocrine pancreatic insufficiency (EPI). Folate is absorbed in the proximal small intestine only and therefore low serum folate levels are indicative of disease affecting the proximal small intestine. Small intestinal bacterial overgrowth (SIBO) is currently a debated topic. Abnormal levels of cobalamin and folate previously supported a diagnosis of (SIBO) although the gold standard for diagnosis required quantitative, anaerobic culture of duodenal juice, which is problematic to obtain. Gastroenterologists recently shifted their focus to the immunopathologic effects of various enteric bacterial populations on the induction and propagation of disease and now prefer to use the term "antibiotic-responsive diarrhea" (ARD).

Survey abdominal radiographs are usually low yield in most animals with chronic diarrhea, but are still indicated in suspected animals with partial intestinal obstruction (due to a foreign body, masses, intussusceptions) or gastric dilation with volvulus. Abdominal ultrasound is more sensitive for the detection of abdominal masses, intestinal thickening, mesenteric lymphadenopathy, and intussusceptions. It also allows visualization of bowel layers, which is very helpful in cases of intestinal lymphangiectasia with the classical "tiger-stripe" hyperechoic appearance to it. Ultrasound guided mass aspiration or percutaneous biopsies are effective, non-invasive diagnostic procedures. Contrast radiography and fluoroscopy are indicated for diagnosing intestinal motility disorders or partial obstructions.

Endoscopic evaluation is valuable for the diagnosis of intestinal mucosal disorders. It is minimally invasive, can be highly rewarding in cases of chronic small intestinal diarrhea and allows concurrent opportunity for duodenal aspirate for Giardia. It is limited by the length of the scope, often precluding examination of the jejunum and doesn't differentiate motility disorders, secretory diarrheas or brush border enzyme defects. Initial rigid colonoscopy is often best for chronic large intestinal diarrhea and allows visualization of the descending colon. Flexible colonoscopy allows evaluation of the transverse and ascending colon, cecum and sometimes the ileum. Proper preparation is required and regardless of method (endoscopic, laparoscopic, etc), even if presented with grossly normal mucosa, multiple biopsies should be obtained. Multiple full-thickness intestinal biopsies as well as mesenteric lymph nodes should be taken if accessible. The proposed standardized intestinal histological evaluation system would significantly aid the veterinary community.

Fecal culture is a low-yield diagnostic. If bacterial colitis is suspected (concurrent acute onset bloody diarrhea and history of possible exposure, including raw diets) the feces can be cultured for specific pathogens such as Campylobacter jejuni,Clostridium difficile and Salmonella. ELISA's for diagnosis of Clostridium perfringens and Clostridium difficile are commercially available. PCR-based tests are being used more to differentiate Campylobacter species and identify Salmonella. Salmonella is infrequently isolated from patients with diarrhea, less than 2%, although increases significantly in animals fed raw diets.

References available on request