GI Function Tests: Why Clinicians Should Use Them
Grant Guilford New Zealand
The standard veterinary gastrointestinal workup varies little and centers on endoscopic examination of the stomach, duodenum and colon. Veterinarians take a history, perform a physical examination, and acquire a database (CBC, serum chemistry profile, urinalysis and one or more fecal flotations). This may be complemented by a fecal culture and serum assays of TLI, cobalamin/folate, FeLV, FIV and T4. If no answer is obvious by this stage, an elimination trial may be tried to rule out adverse reactions to foods. The next step is usually survey abdominal radiographs, abdominal ultrasound, endoscopy and biopsy, or a combination thereof. The pressure then comes on the pathologist to find something in the biopsy samples. Understandably in this situation, the normal complement of gut-associated lymphoid tissue starts to be regarded with great suspicion and before long we have “diagnosed” yet another case of mild inflammatory bowel disease.
Is this a satisfactory state of affairs for veterinary gastroenterology? I don’t believe so. Most body systems are affected by ill-defined “symptom” complexes that are tentatively given labels (such as miliary dermatitis, FLUTD, IBD, and IBS) by the clinicians who first recognise the characteristic pattern of clinical signs. Unfortunately, as others identify the same symptom complex the “label” becomes fashionable and very soon assumes the respectability of a “diagnosis.” Does the use of such generic labels as “diagnoses” compromise clinical practice at all? Usually not, because very often a characteristic symptom complex can be quickly and effectively dealt with by the corresponding “treatment complex.” Yet, there can be a casualty of this approach. The frequent use of such terms tends to reduce the profession’s motivation to obtain diagnoses that are more accurate. There is a tendency to “rest on our laurels” and make comforting statements such as “80% of the dogs an cats in my practice that present with chronic vomiting have “inflammatory bowel disease.” This conveniently ignores the fact that the so-called inflammatory bowel disease may have been food sensitivity, a mucosal permeability barrier defect, a motility disorder, an undiagnosed infection, a small intestinal bacterial overgrowth, or even an incipient lymphoma.
So where should veterinary gastrointestinal diagnostic method go from here? It is quite clear we have a lot to learn about the diagnosis of gastrointestinal infectious disease. In addition, we are a long way from understanding the significance of a single aspirate of duodenal fluid that reveals a higher than average bacterial number (i.e., so called “small intestinal bacterial overgrowth”). We also have a lot to learn about the interpretation of bowel biopsies and have only recently ventured into the complex area of subtyping lymphocytes. Similarly, our knowledge of the value of measuring mucosal inflammatory mediators is in its infancy. Worst of all, we seem to have neglected the entire area of assessing bowel function and replaced this with an emphatic belief that we can subcharacterise (i.e., “diagnose”) all bowel disease by morphology or culture. This cherished misconception ignores the fact that bowel functions such as motility, secretion, permeability, absorption, visceral sensitivity and oral tolerance can be compromised without any morphologic abnormality. The inescapable conclusion is that bowel function tests are necessary to reach an accurate diagnosis of gastrointestinal complaints.
Bowel Function Tests
Why aren’t bowel function tests more commonly used? The answer is complex and draws on a pragmatic view of the purpose of a diagnostic work-up. Clients pay veterinarians to pursue a diagnostic work-up to help us find a better way to treat their animal—not to reach a diagnosis per se. Thus, the purpose of a diagnostic work-up is to determine the type of disease process resulting in the clinical signs and to subclassify that disease process to the level necessary to optimize patient care. Experienced clinicians do not countenance performing a test unless they are convinced the results of that test will influence prognosis or the way they will treat the patient. For a function test to regularly influence prognosis or treatment, functional bowel disorders must be common; the tests must have good diagnostic accuracy, an acceptable risk/benefit and cost/benefit ratio; and suboptimal care must result from failure to recognize the functional disorder. Now let us examine specific bowel functions to determine if practical function tests are available and are indicated in modern day gastrointestinal work-ups.
Collectively, maldigestion and malabsorption are common. Maldigestion due to exocrine pancreatic insufficiency can be conveniently and accurately diagnosed by the TLI test. Although not a classical function test, it has proved to have similar diagnostic accuracy for EPI than older tests of digestive function such as BT-PABA. Maldigestion does occur for reasons other than EPI, but because these other conditions are relatively uncommon (or unlikely to be clinically significant), the TLI suffices as an excellent defacto bowel function test. Suboptimal patient care occurs if maldigestion is not diagnosed. Therefore, a serum TLI test should be a routine part of any work-up of canine small bowel diarrhea.
The need for a function test for intestinal absorption is reduced by the fact that osmotic diarrhea can be conveniently recognized clinically (e.g., stops when the patient is fasted). Osmotic diarrhea due to malabsorption can be differentiated from that due to maldigestion by the TLI. Once malabsorption has been identified, the next question is: why? The answer to this question requires diagnostic tests such as endoscopy and bowel biopsy rather than tests of intestinal absorption. However, there are a select number of circumstances in which it can be helpful to test intestinal absorptive function. One such situation is in the diagnosis of cats demonstrating idiopathic weight loss without diarrhea. In my experience, lack of diarrhea does not rule out malabsorption in cats. Unlike dogs, cats have a remarkable ability to concentrate their feces against a high osmotic gradient, which means that malabsorbed food particles can reach high concentrations before provoking diarrhea. In dogs, the two most common situations in which I have found measurement of bowel absorption useful is in evaluating the veracity of diagnoses of mild IBD and in quantifying malabsorption for research studies. In the former situation, I am looking for a functional abnormality (e.g., malabsorption) to help me assess the clinical significance of mild cellular infiltrates in the small intestine. The hypothesis is that mild infiltrates with an associated malabsorption are more likely to be clinically significant than mild infiltrates without demonstrable malabsorption. Lastly, tests of absorptive function are likely to be of value in young animals suspected of disaccharidase deficiency. The bowel absorption test I prefer is the breath hydrogen test. I am not a fan of the xylose, fat absorption, or vitamin B12/folate tests although others find the latter test valuable.
Motility disorders (both primary and secondary) are collectively common. They are difficult to recognize solely based on clinical signs, and suboptimal care can result if they are not recognized. Clinicians aware of depressed bowel motility usually choose to treat the patient with prokinetic drugs or dietary changes (e.g., gruels). The risk/benefit ratio of the currently available tests of bowel motility is uniformly low. However, their cost/benefit ratio varies with scintigraphy and fluoroscopy being relatively expensive in comparison to radiographic procedures. The diagnostic accuracy of scintigraphy and radiopaque markers is high in comparison to studies with barium suspensions. Because of their convenience, cost-effectiveness, and established diagnostic accuracy, radiopaque markers (BIPS, MedID) have become the author’s technique of choice for assessing gastric emptying and small and large intestinal transit and for ruling out partial bowel obstructions. They are now a routine part of my diagnostic work-ups of chronic vomiting.
Oral tolerance is another bowel function that is ignored at the peril of the clinician. A failure of oral tolerance results in food allergy that can cause acute or chronic gastrointestinal complaints with the latter impossible to differentiate from IBD without dietary elimination-challenge tests. Dietary trials should be a routine part of all gastrointestinal work-ups. Another way to assess oral tolerance is to perform a gastroscopic food sensitivity test (GFST). This test is useful for those who want a direct assessment of the reaction of the gastrointestinal mucosa to food antigens. It is analogous to patch testing the skin and has the potential to detect subclinical type 1 hypersensitivities underlying bowel dysfunction. The author finds this test most useful for determining dietary proteins to be avoided in complicated canine IBD patients that have been exposed to a multitude of diets. If a welt occurs at the site at which food antigen is applied to the gastric mucosa, that protein source is avoided in the patient’s therapeutic diet. The GFST is performed during the same endoscopy procedure by which gastrointestinal biopsy specimens are obtained. The indications for GFST have been reduced with the advent of protein hydrolysate diets, because hydrolysate diets avoid the need to make an accurate choice of a novel (intact) protein diet to manage food allergic patients.
The maintenance of mucosal permselectivity is a critical bowel function and abnormalities of permeability appear relatively common. Numerous tests of bowel permeability have been advocated including tests that evaluate the passage of molecules from gut to blood (e.g., simple sugars) and those that measure loss of plasma protein into the gut (for diagnosis of protein-losing enteropathy). In general, these tests pose few risks but some are relatively expensive and difficult to perform. They are useful for research but have not yet become routine in clinical practice partly because the recognition of increased permeability may not affect the patient’s management. The most frequently proposed clinical use of sugar permeability tests is to screen for subclinical bowel disease. At IVABS, we have developed a simple blood test of bowel permeability to dietary proteins and hope to develop this to assist a number of clinical decisions including whether to employ a protein hydrolysate diet. It will be a year or two before private practitioners can routinely gain access to practical tests of bowel permeability suitable for clinical purposes.
There are currently no practical tests of gastrointestinal tract secretory function available. In the future, rectal dialysis bags may be useful for this assessment. Currently, practitioners must rely on recognition of the classic clinical sign of secretory diarrhea, i.e., diarrhea that continues during fasting.
Abnormalities of visceral sensation are likely to underpin irritable bowel syndrome in dogs as is suspected in people. Currently practical methods of assessing visceral sensation in small animal clinical patients have not been developed, but the response to graded distension of a rectal balloon is likely to be informative once a standardized protocol is developed.
In conclusion, practical tests of some bowel functions (digestion, absorption, oral tolerance, and motility) are available to clinicians and add value to diagnostic work-ups. The development and refinement of clinically applicable tests of gastrointestinal function is a high priority for the future.
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