Chapter 11 Diarrhea
Diarrhea is an increase in the frequency, fluidity, or volume of feces1 that is best characterized by duration (acute versus chronic), pathophysiologic mechanism, and anatomic location. Diarrhea is considered acute if it lasts for less than 14 days, and chronic when it persists for more than 14 days. Acute, self-limiting diarrhea is a relatively common problem in dogs and cats and usually requires minimal diagnostic testing and therapy. In contrast to most animals with acute diarrhea, chronic diarrhea can be particularly challenging to diagnose, because most animals will not respond to empirical therapies, necessitating a well-formulated and cost-effective diagnostic and therapeutic plan. Specific therapeutic modalities are based upon a definitive diagnosis or histologic characterization of intestinal biopsies.
Although diarrhea is the primary sign of intestinal dysfunction, there are a number of secondary clinical signs that may become the principal one for which the animal is presented, and it is noteworthy that diarrhea may or may not accompany these secondary clinical signs. These secondary signs include abdominal distention, abdominal pain, borborygmus, dehydration, flatulence, halitosis, melena, hematochezia, polydipsia, polyphagia, tenesmus, vomiting, and weight loss. Animals may present with alterations in appetite ranging from polyphagia to anorexia, and these same alterations in food intake can be recognized as a consequence of disease progression (e.g., inflammatory bowel disease, intestinal lymphangiectasia, and lymphoma). Weight loss is often associated with nutrient malabsorption of diffuse mucosal disease. Vomiting can be associated with a variety of gastrointestinal disorders and is relatively common in animals with inflammatory bowel disease (IBD). Colorectal disorders are often associated with tenesmus, dyschezia, and large bowel diarrhea characterized by hematochezia, increased mucus on feces, marked increase in defecation frequency, and a reduction in fecal volume.
Pathophysiology and Mechanisms
There are four major pathophysiologic mechanisms that can result in diarrhea, although more than one mechanism can contribute to diarrhea simultaneously.
Osmotic diarrhea is caused by unusually large amounts of poorly absorbable osmotically active solutes in the intestinal lumen. Osmotic diarrhea occurs with malabsorptive disorders where nutrients are maldigested or malabsorbed, remain within the intestinal lumen, and osmotically attract water. Exocrine pancreatic insufficiency is an example of an osmotic diarrheal disorder. Retention of nutrients can lead to alterations in intestinal microflora and fermentation of carbohydrates, further increasing numbers of osmotically active particles. The fecal water output in osmotic diarrhea is directly related to fecal output of the solute or solutes that are exerting an osmotic gradient across intestinal mucosa. Electrolyte absorption is unaffected by these osmotically active substances, and fecal water typically contains very little unabsorbed sodium or potassium.2 This is the basis for the calculation of the “fecal osmotic gap.” In this calculation, the difference between luminal osmolality (equal to body fluid osmolality, approximately 290 mOsm/kg, because the colon cannot maintain an osmotic gradient against plasma) and osmolality of luminal contents contributed by fecal electrolytes is estimated. The contribution of fecal electrolytes is calculated as twice the sum of sodium and potassium ions to account for the anions that accompany these cations. A fecal osmotic gap greater than 50 mOsm/kg suggests osmotic diarrhea.2 One of the major hallmarks of osmotic diarrhea is that diarrhea resolves when the patient stops ingesting the poorly absorbable solute.
Secretory diarrhea is caused by abnormal ion transport in intestinal epithelial cells. The most common cause of secretory diarrhea in dogs and cats are abnormal mediators resulting in changes in intracellular cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), calcium, and/or protein kinases, which in turn cause a decrease in neutral sodium chloride absorption or an increase in chloride secretion.3 Such mediators include endogenous enteric hormones or neuropeptides, inflammatory cell products, bacterial enterotoxins, laxatives, fatty acids, and bile acids (see Chapters 1 and 57 for more detail). Secretory diarrhea has two important distinguishing features; first, fecal osmolality can be accounted for by sodium, potassium, and their accompanying anions, and thus the osmotic gap is small; and second, the diarrhea usually persists despite fasting because the diarrhea is caused by abnormalities in ion transport that have nothing to do with food. Enteropathogenic Escherichia coli and IBD are examples of secretory diarrheas.
Increased Mucosal Permeability
Increased mucosal permeability causes loss of fluids, electrolytes, proteins, and red blood cells into the intestinal lumen. Erosive or ulcerative enteropathies, inflammatory (IBD), or neoplastic disorders (intestinal lymphoma) are common causes of alterations in mucosal permeability.
Experimental studies in dogs show that abnormal ileal and colonic motility patterns may contribute to clinical symptomatology of IBD.4,5 The two major motor abnormalities in intestinal inflammation are suppression of phasic contractions, including migrating motor complexes, and stimulation of giant migrating contractions (GMCs), the powerful ultrapropulsive contractions that usually propagate uninterruptedly form the point of their origin in the small intestine to the terminal ileum and often into the colon.4 Stimulation of GMCs in fasting and fed states produces ultrarapid transit of intestinal and pancreaticobiliary secretions and undigested food into the colon to increase its osmotic load with resultant diarrhea.4 Platelet-activating factor (PAF) may be one of the inflammatory response mediators that stimulates GMCs,5 and it is synthesized and released from several immunocytes, including polymorphonuclear (PMN) leukocytes, monocytes, macrophages, mast cells, and eosinophils.5
Box 11-1 lists differential diagnoses for acute and chronic diarrhea in dogs and cats, as well as those disorders that are potentially life-threatening. Many cases of chronic diarrhea can manifest initially as acute diarrhea. Localization of the disease process into “small bowel” versus “large bowel” has some limitations, as many diarrheal diseases with primary manifestations of one compartment (large bowel or small bowel) may have diffuse gastrointestinal (GI) involvement (large and small bowel). This point is underscored by a study in 40 dogs suggesting that routine collection of ileal biopsies is warranted in dogs with colonopathy, and that routinely sampling of duodenum and ileum increases the diagnostic yield compared to biopsy of one anatomic site.6 Regardless, the initial differentiation into small and large bowel components helps to further clarify the medical investigation (see Figs. 11-1 and 11-2).
Differential Diagnoses for Acute and Chronic Diarrhea
Differential diagnoses for acute and chronic diarrhea in dogs and cats, with annotation of potentially life-threatening causes of disease.
Parasitic helminths,‡ protozoa‡
Bacterial Salmonella,#,* Campylobacter,* Clostridium perfringens,#,* Clostridium difficile,#,* E. coli,#,*
Viral parvovirus,#,* coronavirus,* feline leukemia virus (FeLV),† feline immunodeficiency virus (FIV)†
Fungal histoplasmosis,#,† Pythium,#,† cryptococcosis#,†
Exocrine pancreatic insufficiency†
Functional Ileus/Mechanical Obstruction
Toxemia (pyometra, peritonitis)#,*
Leiomyosarcomas (gastrointestinal stromal tumors)#,‡
Evaluation of the Patient
Awareness of the importance of the animal’s signalment and breed predilections for GI disease can facilitate development of a differential diagnosis for the particular animal. A 3-year-old Yorkshire Terrier dog with a 2-month history of small intestinal diarrhea, weight loss, and progressive abdominal distention has a signalment and history suggestive of intestinal lymphangiectasia. Likewise, a young Boxer dog with a 3-month history of tenesmus, hematochezia, increased stool frequency, and mucoid stools could be consistent with histiocytic colitis. Tunnel vision should be avoided, however, as it is plausible that a Boxer dog could have diarrhea from any number of underlying causes.
History and physical examination often indicates the anatomic localization and severity of the disease process, and it helps prioritize differential diagnoses. History should ensure that systemic causes of diarrhea are not overlooked. A comprehensive history should also identify important predisposing factors (e.g., exposure to parasites, infectious agents, drugs, toxins). It is equally important to fully characterize the nature of diarrhea and appearance of feces (Table 11-1). For dogs with a history of tenesmus, it is pivotal to determine whether signs are secondary to colitis or to a discrete mass or polyp in the colorectal region. The latter is often associated with a change in the appearance of the stool (“ribbon-like,” “pencil-thin”) in the absence of a marked increase in frequency of bowel movements or increased fecal mucus as seen with colitis. Likewise, absence of clinical signs of diarrhea does not rule out severe underlying intestinal disease; dogs with protein-losing enteropathy (PLE) may have anorexia and weight loss without associated vomiting and diarrhea. Failure to consider the role of diet or dietary supplements in precipitating or alleviating the diarrhea can cause delayed diagnosis or improper dietary recommendations. Box 11-2 outlines specific questions that should be addressed.
|Differentiation of small versus large bowel diarrhea based upon clinical signs and the physical appearance of feces.|
|Sign||Small Bowel||Large Bowel|
|Frequency of defecation||Normal to mildly increased||Markedly increased|
|Fecal volume||Normal to increased||Decreased|
|Fecal mucus||Usually absent||Often present|
|Vomiting||May be present||May be present|
|Steatorrhea||May be present||Absent|
* Caution should be heeded with the oversimplistic attempts at compartmentalizing the diarrhea into a small bowel versus a large bowel compartment, as many diarrheal diseases can have diffuse involvement histologically.
Questions that Should be Asked in Patients with Diarrhea
• What is the clinical course or onset of the diarrhea (congenital or acquired; abrupt or gradual in onset; continuous or intermittent)?
• What is the duration of signs?
• What are the physical characteristics of the diarrhea?
• Are there any alleviating or exacerbating factors for the diarrhea such as dietary changes, antibiotic administration, stress, recent travel, or recent kenneling?
• What is the animal’s past medical history, and is this diarrhea episode a new problem or a recurrent one? If recurrent, how was the diarrhea managed previously, and what was the outcome?
• What is the animal’s anthelmintic and vaccination history?
• Are any other pets in the household similarly affected?
• Is the diarrhea associated with any other systemic (e.g., polyuria/polydipsia) or gastrointestinal signs such as weight loss, vomiting, and anorexia?
A thorough physical examination helps determine severity and likely origin of the problem. Careful attention should be placed on physical appearance of the animal (emaciation or malnutrition suggestive of malassimilation from IBD, intestinal lymphoma, lymphangiectasia, or pancreatic insufficiency); detection of fever (infectious enteropathy or breakdown of the intestinal mucosal barrier); abdominal effusion and edema (secondary to protein losing enteropathies); and mucous membrane pallor (secondary to intestinal blood loss). Abdominal palpation is performed for detection of mass lesions, thickened bowel loops (neoplasia, intussusception, IBD, fungal enteropathies, mesenteric lymphadenopathy), or pain (bowel inflammation, pancreatitis, peritonitis, ischemia of bowel, and gas-associated bowel distention). In cats the thyroid region should be carefully palpated for thyroid nodules, and the kidneys and liver examined for changes in size and contour. Digital rectal palpation is important for detection of rectal masses or irregular thickening of rectal wall, colorectal strictures, and collection of feces for gross inspection and further evaluation. Digital rectal palpation of the rectum in cats is usually performed under general anesthesia or deep sedation. Macroscopic examination of a fresh fecal specimen is essential for assessment of bulk, color, consistency, detection of blood and mucus, and detection of foreign material. Small bowel diarrhea is generally free of grossly visible mucus or red blood, but prominent steatorrhea may cause the feces to appear lighter in color. Acholic or pale feces can also be seen in association with extrahepatic bile duct obstruction causing a lack of the bile pigment stercobilin in the feces. Rapid intestinal transit time can be associated with yellow or green stools caused by incomplete metabolization of bilirubin.
Laboratory Evaluation and Tests
An important part of the workup is determining whether the animal has a self-limiting or potentially life-threatening problem. This distinction is pivotal as it determines the level of diagnostic testing and therapy needed and helps determine the likelihood of an animal having a self-limiting diarrhea that could be managed empirically, or an animal having a chronic disease that warrants hospitalization and a more comprehensive workup. This distinction is based on a comprehensive history, thorough physical examination, clinical experience and judgment, and awareness of the differential diagnoses for the diarrhea. Animals showing one or more of the following physical examination findings or signs at presentation warrant a more comprehensive workup and possible hospitalization: fever; abdominal pain; abdominal effusion; organomegaly; moderate to severe dehydration; severe lethargy; melena or hematochezia; mucous membrane pallor; jaundice or congestion; palpable abdominal mass or dilated loop of bowel; frequent vomiting; or other signs of systemic disease such as polyuria/polydipsia.
For animals with acute, mild diarrhea that appear relatively healthy on physical exam and are deemed likely to have a self-limiting gastroenteropathy, a minimum database consisting of centrifugation fecal flotation using zinc sulfate (specific gravity of 1.18 to 1.2) complemented with a fecal enzyme-linked immunosorbent assay (ELISA) or immunofluorescence test for Giardia is typically adequate for assessment of parasitic disease. In addition, measurement of hematocrit and total protein are helpful to assess hydration status. Fecal cytology in diarrheic dogs is a low-yield diagnostic test because finding of “safety pin”-shaped endospores consistent with Clostridium perfringens are of no diagnostic value. Their detection does not correlate with the presence of C. perfringens enterotoxin, the putative virulence factor associated with diarrhea.7,8 Likewise, detecting “spiral-shaped” bacteria assuming the appearance of “seagulls” is insufficient for a diagnosis of Campylobacter-associated diarrhea because spiral-shaped bacteria resembling Campylobacter spp. are commonly identified in feces from healthy, nondiarrheic dogs and cats. Isolation of the microaerophilic organism utilizing selective culture media is a far more sensitive diagnostic tool compared with stained fecal smears.9 In contrast to direct fecal cytology, exfoliative rectal cytology is a useful diagnostic test in dogs and cats with signs of colitis, and is best indicated for diagnosis of specific enteropathogens such as Histoplasma spp., Pythium insidiosum, or Prototheca,10 or for colonic neoplasms such as lymphoma and carcinoma.
Animals with potentially life-threatening diarrhea or diarrhea that has not responded to conventional therapeutic approaches within 2 to 4 weeks warrant the time and effort required to make a specific diagnosis. The decision of whether to embark on an attempt to make a specific diagnosis usually depends on the nature of the problem, the availability of specific diagnostic facilities, and any client constraints (e.g., financial). For undiagnosed chronic or life-threatening diarrhea, the minimum database should include a complete blood count (CBC), a serum biochemistry profile, a urinalysis, a centrifugation fecal flotation using zinc sulfate, and a direct smear of saline admixed fresh feces for protozoa. A fecal ELISA for parvovirus in puppies should be considered based on signalment, vaccination history, clinical signs, and hematologic findings. The minimum database is performed to determine whether primary GI or metabolic/systemic disorders are associated with diarrhea. Baseline testing should also include specific tests for common disorders known to be likely in a particular animal (e.g., serum thyroxin testing in a 14-year-old cat with a history of chronic weight loss, diarrhea, and polyphagia).
Baseline Laboratory Tests
Complete Blood Count
The complete blood count may reveal an eosinophilia secondary to endoparasitism, eosinophilic enteritis, hypoadrenocorticism, or mast cell neoplasia. Anemia may result from enteric blood loss or from depressed erythropoiesis caused by systemic disease, chronic inflammation, or malnutrition. A peripheral neutrophilia could reflect stress, inflammation, or infection. Finding a left shift with toxic neutrophils should warrant an aggressive workup for underlying causes (infection, immune disease, etc.). Lymphopenia is a relatively common finding in dogs with intestinal lymphangiectasia.