Workup of dogs with chronic diarrhea: The basics (Proceedings)

Diarrhea is one of the most common clinical signs seen in dogs. There are many different approaches for the work-up of chronic diarrhea. Differences may be due to certain diagnostic modalities that may or may not be available, they may be due to differences in clinical expertise of the clinician, they may be due to a particularly common problem in a geographic region, such as fungal disease, or they may be due to a difference in opinion between clinicians. Finally, the work-up needs to be guided by the urgency at hand. For example rapid weight loss of a patient requires a more aggressive diagnostic approach than if there is no weight loss at all.

History and physical examination

As for any clinical problem a careful history is important. It should include questions about the immediate as well as the past clinical history of the patient that is being presented, the environment and the husbandry, especially as it relates to the diet, and the clinical history of other pets in the household. In addition to a careful history, a comprehensive physical examination provides a good initial database. Special attention should be given to body condition, hydration status, oral examination, abdominal palpation, and a rectal exam.

Endoparasites

If history and physical examination do not reveal any specific indicators for a cause of the diarrhea a reasonable initial approach includes careful fecal examination for evidence of parasitic infestation and treatment with a broad-spectrum anthelmintic agent regardless of the findings on fecal examination. First, a fresh fecal smear should be prepared by mixing a small amount of feces with a drop of saline on a glass slide. The slide is coverslipped and examined under low magnification for the presence of trophozoites from Giardia. Giardia trophozoites show a typical "falling leaf" motion. In addition to the fecal smear, a zinc sulfate flotation should also be performed. The procedure is simple and can be quickly performed. Ova of many common endoparasites can be observed by zinc sulfate flotation. Also, zinc sulfate flotation is the gold-standard method for the diagnosis of Giardia. Giardia cysts can sometimes be confused with yeast. However, Giardia cysts are much larger than yeast and, in contrast to yeast, do contain internal structures.

The true prevalence of gastrointestinal parasites in dogs is unknown and dependant on many factors but given the low cost of evaluating a patient for endoparasitic infestation and the low cost and ease of treatment, fecal examination for evidence of endoparasitic infestation should be routine in any dog with chronic diarrhea.

Differentiation of primary and secondary causes of diarrhea

The most important step for a proper diagnosis is the differentiation of primary and secondary gastrointestinal disease, which can be achieved by performing a complete blood count, a serum chemistry profile, and a urinalysis. Some additional serum should always be collected and frozen for possible future analysis.

A complete blood count may help to identify inflammatory, infectious, or endocrine disorders, as it may reveal anemia or an inflammatory leukogram. The serum chemistry profile, together with specific gravity from the urinalysis is useful to rule out chronic renal failure. Hyperkalemia and hyponatremia may be present in dogs with hypoadrenocorticism. However, it is important to note that not all patients with hypoadrenocorticism show these abnormalities. Some dogs do not lack mineralocorticoids and will not show electrolyte abnormalities, but should still show a lack of an appropriate stress leukogram. Dogs that are suspected of having hypoadrenocorticism should be evaluated with a base-line serum or plasma cortisol concentration and if inconclusive with an ACTH stimulation test. Hypoadrenocorticism, if untreated, can lead to an Addisonian crisis and death and even a weak suspicion of hypoadrenocorticism warrants further testing. Results from the serum chemistry profile also help to rule-out hepatic failure. If there is any doubt about the presence of hepatic failure, serum pre- and postprandial bile acid concentrations need to be evaluated.

Exocrine pancreatic disease can also cause chronic diarrhea. Dogs with exocrine pancreatic insufficiency (EPI) often have soft stools or diarrhea as the most important clinical sign. EPI can easily be diagnosed by measurement of serum TLI concentration. Also, dogs with chronic pancreatitis often present for nonspecific clinical signs and chronic diarrhea may be the only clinical sign reported. If there is any suspicion for chronic pancreatitis, a serum pancreatic lipase immunoreactivity concentration (PLI) should be evaluated. Serum fTLI in only performed at the Gastrointestinal Laboratory at Texas A&M University (www.cvm.tamu.edu/gilab).

Characterization

Once secondary disorders have been ruled out the type of diarrhea should be characterized. In general, small and large bowel diarrhea can be distinguished. Patients with small bowel diarrhea have an increased fecal volume but a normal or only mildly increased frequency of defecation. Blood, if present, is digested causing melena. Patients with large bowel diarrhea often strain to defecate. They also often have fresh blood and an increased amount of mucous covering the feces. Also, weight loss does not usually occur in patients with large bowel diarrhea while patients with small bowel diarrhea may or may not have weight loss. However, this differentiation is not always clear cut and most patients with clinical signs of large bowel diarrhea have more significant disease of the small bowel. In contrast to human beings isolated colitis is rare in dogs. One exception to this is histiocytic ulcerative colitis that mainly occurs in the Boxer and appears to be due to enteroinvasive E. coli. These patients were long believed to be affected with a steroid-resistant type of IBD, but have now been shown to respond well to treatment with enrofloxacin (5 mg/kg PO q 12 hrs for 6-8 weeks).

Many patients with chronic diarrhea do have a normal complete blood count and serum chemistry profile or only have non-specific changes such as mild elevations of hepatic enzyme activities. These patients should be worked up for primary gastrointestinal disease.

Serum cobalamin and folate concentrations are of great diagnostic and therapeutic importance. Serum folate concentration can be decreased in proximal small intestinal disorders, while serum cobalamin concentration can be decreased in distal small intestinal disorders and EPI. In patients with diffuse small intestinal disorders both serum folate and cobalamin concentrations can be decreased. Dogs with small intestinal bacterial overgrowth can have a decreased serum cobalamin concentration and an increased serum folate concentration.

Folate and cobalamin are both water-soluble vitamins that are plentiful in almost all commercial feline diets. However, dietary folate, which is mostly folate polyglutamate, needs to be deconjugated to folate monoglutamate by folate deconjugase, a jejunal brush border enzyme. Folate monoglutamate is absorbed by specific carriers in the proximal small intestine. Therefore, longstanding and severe disorders of the proximal small intestine can lead to folate malabsorption, depletion of folate body stores, and a decreased serum folate concentration. In contrast, many intestinal bacteria produce folate and thus SIBO can lead to increased serum folate concentrations. Dietary cobalamin is bound to dietary protein. In the stomach dietary protein is partially digested by pepsin and HCl and cobalamin is being released. However, cobalamin immediately binds to R-protein. The R-protein in turn is digested by pancreatic proteases in the small intestine. Free cobalamin binds to intrinsic factor, released mostly in pancreatic juice. These cobalamin-intrinsic factor complexes are then absorbed through specific receptors in the ileum. Therefore, severe and longstanding disorders of the distal small intestine as well as exocrine pancreatic insufficiency will lead to cobalamin malabsorption, depletion of cobalamin body stores, and to a decreased serum cobalamin concentration.

Serum cobalamin is not only of diagnostic but also of therapeutic interest. Patients with severe cobalamin deficiency often do not respond to therapy of the underlying gastrointestinal disorder until cobalamin is supplemented. Cobalamin supplementation has to be by parenteral cobalamin administration (250-1200 µg per injection, SC q 7 days for 6 weeks, q 14 days for 6 weeks, q 30 days for one injection, reevaluate serum cobalamin concentration one month later).

Outlook

For all patients that do not have secondary chronic diarrhea or parasitism there are two choices, more diagnostic tests or a therapeutic trial. The choice ultimately depends on the urgency of the case and the goals of the owner.