EPI in Cats
Untargeted analysis of the serum
metabolome in cats with exocrine pancreatic
Patrick C. Barko *, David A. Williams
Department of Veterinary Clinical Medicine, University of Illinois at Urbana-Champaign, Urbana, Illinois,
United States of America
Exocrine pancreatic insufficiency (EPI) causes chronic digestive dysfunction in cats, but its
pathogenesis and pathophysiology are poorly understood. Untargeted metabolomics is a
promising analytic methodology that can reveal novel metabolic features and biomarkers of
clinical disease syndromes. The purpose of this preliminary study was to use untargeted
analysis of the serum metabolome to discover novel aspects of the pathobiology of EPI in
cats. Serum samples were collected from 5 cats with EPI and 8 healthy controls. The diagnosis of EPI was confirmed by measurement of subnormal serum feline trypsin-like immunoreactivity (fTLI). Untargeted quantification of serum metabolite utilized ultra-highperformance liquid chromatography-tandem mass spectroscopy. Cats with EPI had significantly increased serum quantities of long-chain fatty acids, polyunsaturated fatty acids,
mevalonate pathway intermediates, and endocannabinoids compared with healthy controls.
Diacylglycerols, phosphatidylethanolamines, amino acid derivatives, and microbial metabolites were significantly decreased in cats with EPI compared to healthy controls. Diacyclglycerols and amino acid metabolites were positively correlated, and sphingolipids and longchain fatty acids were negatively correlated with serum fTLI, respectively. These results
suggest that EPI in cats is associated with increased lipolysis of peripheral adipose stores,
dysfunction of the mevalonate pathway, and altered amino acid metabolism. Differences in
microbial metabolites indicate that feline EPI is also associated with enteric microbial dysbiosis. Targeted studies of the metabolome of cats with EPI are warranted to further elucidate the mechanisms of these metabolic derangements and their influence on the
pathogenesis and pathophysiology of EPI in catsUntargeted analysis of the serum metabolome in cats with exocrine pancreatic insufficiency
Patrick C. Barko ,David A. Williams
Published: September 30, 2021
Abdominal ultrasound and clinicopathologic findings in 22 cats with exocrine pancreatic insufficiency
Mylène Auger,Constance Fazio,Joerg M. Steiner,Dominique G. Penninck,Gwendolyn J. Levine,John F. Griffin IV,Cary M. Springer
First published: 01 October 2021 https://doi.org/10.1111/jvim.16267
The most common clinical sign was weight loss (15/22 cats). Chronic enteropathy was the most common concurrent disease (13/22 cats). In 39% of cats, the pancreas had minimal or no sonographic alterations. Pancreatic duct dilatation (>2.5 mm), pancreatic duct tortuosity with variable diameter, or both were seen in 6/13 cats. The pancreatic parenchyma was subjectively thin in 6 cats. A significant relationship was found between subjectively thin pancreatic parenchyma and increased pancreatic duct size : pancreatic thickness ratio (P = .004). Diffuse gastrointestinal dilatation with echogenic content was observed in 8/22 cats.
Exocrine pancreatic insufficiency often causes minimal to no sonographic pancreatic changes. Nonetheless, the findings of thin pancreatic parenchyma, pancreatic duct dilatation, or diffuse small intestinal dilatation with echogenic contents in cats with unexplained weight loss or unformed feces should raise clinical suspicion for EPI.I'm a paragraph. Click once to begin entering your own content. You can change my font, size, line height, color and more by highlighting part of me and selecting the options from the toolbar.
Skinny old cats: Why some senior cats lose weight. What’s going on?
(Sponsored by Purina Veterinary Diets)
Nov 12, 2014
CUSTOM VETERINARY MEDIA
Decline in body weight is common in cats that are older than 11 years.1 Sometimes this loss is readily attributable to apparent disease, but in many cases, there are no obvious signs of illness and routine diagnostic approaches fail to reveal evidence of an underlying problem.2,3 Energy requirements of older cats apparently do not decline as markedly as they do in dogs and people, perhaps because physical activity does not decrease as much with age in cats. Indeed, the maintenance energy requirement of older cats may increase rather than decrease.3,4 Although cats might be expected to regulate their energy intake to compensate for these changes to maintain body weight, that clearly is not always the case.4,5
It has been recognized for many years that both protein and fat digestibility decrease in many apparently normal cats after 10 years of age. While the cause of the decreases remains unclear, the changes are quite marked in some individuals and in particular can be dramatic with regard to fat digestibility.4,5 Often these changes are not readily apparent from casual observation of feces and may only be verified if fecal fat content is quantified by appropriate analytic testing. Methods for such testing are rarely available for evaluation of veterinary patients, even at referral centers.
Whatever the explanation for weight loss and decline in nutrient digestibility in older cats, progressive decline in body weight has been reported in the two years before death from a variety of seemingly unrelated diseases. As cats live increasingly longer lives and receive attentive health care, this weight loss is more frequently recognized. In this article, I will review what is known about common age-related changes and what may be done to halt or reverse the decline in body weight that is apparently a predictable prelude to death.3,4,6
Attributable weight loss
Well-recognized causes of weight loss in old cats include chronic renal disease, diabetes mellitus, hyperthyroidism, inflammatory bowel disease (IBD), exocrine pancreatic insufficiency, and dental problems. Most are readily suspected and confirmed based on physical examination and routine laboratory testing. At times, selected additional testing of parameters such as serum thyroxine, serum trypsin-like immunoreactivity, cobalamin and folate, dental radiography (Figures 1A & 1B), or gastrointestinal (GI) endoscopy and biopsy may be necessary. Despite thorough investigation, however, the underlying cause of even severe weight loss can be remarkably difficult to establish conclusively.
Figure 1A. Dental disease can contribute to weight loss in senior cats. Tooth resorption of the left maxillary canine (a) and 3rd premolar in a cat (b). Small focal areas of inflammation are apparent on the left maxillary 3rd premolar (b) and the left mandibular 4th premolar (c). The left mandibular 3rd premolar is missing, leaving focal residual inflammation (d).
Figure 1B. In the same cat, an intraoral bisecting angle dental radiograph of the left maxilla shows an unsuspected extensive tooth resorption at the cementoenamel junction of the distal left maxillary canine tooth (a). Tooth resorption affecting the root and crown of the 3rd premolar is also apparent (b). (Courtesy of the Veterinary Dental Service Library, University of Illinois)
Unattributed weight loss
Subtle weight loss may not even be noted unless careful records of body weight and body condition scores are kept over repeated veterinary examinations. Similarly, moderate increases or decreases in food or water intake will probably go unnoticed by most owners. Even when the most attentive owners provide the best veterinary care for their cats, a substantial proportion of senior cats will experience weight loss, despite being in otherwise good health and exhibiting no detectable change in food intake.
Figure 2. Fat digestibility (by percentage) in cats ranging in age from 8 to 18 years (n = 208)
Click here to edit text Evidence indicates that, in these older cats with no apparent classic diseases to explain the weight loss, there is an age-related decline in food digestibility.3 There is a significant (p < 0.0001) negative correlation (r = −0.76) between age and fat digestibility (Figure 2). The incidence of low fat digestibility increases with age, affecting 10% to 15% of mature cats (8 to 12 years old) and 30% of geriatric cats (> 12 years old). In some geriatric cats, fat digestibility was found to be as low as 30%, and the only clinical signs were large stools (not frank diarrhea) and low body weight.
Figure 3. Protein digestibility (by percentage) in cats ages ranging in age from 8 to 18 years (n = 208).
There is also a significant (p < 0.0001) negative (r = −0.66) correlation between age and protein digestibility (Figure 3). Low protein digestibility also seems to affect mature and geriatric cats. Although the incidence of low protein digestibility is lower than that of fat digestibility, about 20% of cats older than 14 years show protein digestibility lower than 77%. The incidence of low fat and protein digestibility tends to occur in the same cats. A marked decline apparently becomes particularly prevalent after around age 10 (Figures 4 & 5).
Figure 4. Percentage of cats with low fat digestibility by age (pooled data from four colonies).
Figure 5. Percentage of cats with low protein digestibility by age (pooled data from four colonies).
It is perhaps not surprising that these changes were correlated with several other measures of health or well-being, including serum vitamin E (tocopherol), vitamin B12 (cobalamin), skin thickness, body fat, and body condition score. Overall, while obesity tends to be the predominant body-mass concern in cats between 7 and 12 years of age, in those older than 12 years, obesity is rare and being underweight is a far greater life-threatening risk factor (Table 1 and Figure 6).3
Figure 6. After 12 years of age, there is marked decline in body weight among cats, which supplants obesity as a common life-threatening condition.
Table 1. Incidence of Feline Obesity and Underweight by Age*
The cause or causes of this decline in nutrient digestibility remain unknown but presumably reflect enteropathy of some type. In some cases, this intestinal dysfunction may overlap with what is loosely classified as (idiopathic) IBD. Some cats compensate for the loss in digestive function by eating more and, therefore, exhibit no weight loss. It is important to recognize that many cats show only subtle changes in stool characteristics (slightly larger volumes of stool with a more clay-like consistency) but not frank diarrhea, even when steatorrhea is marked.
Regardless of the precise cause or causes, weight loss in otherwise healthy older cats and changes in fecal characteristics should be investigated, as should malabsorption. Thorough physical examination, routine complete blood count, serum chemistry profile, urinalysis, and fecal examination are all indicated, as are radiographic and ultrasonographic evaluations as appropriate. If nothing specific is found to explain the weight loss, the next step is to measure serum thyroxine, feline pancreatic lipase, feline trypsin-like immunoreactivity, and cobalamin/folate levels. I recommend that these be determined concurrently because studies have indicated that about 50% of hyperthyroid cats have evidence of concurrent intestinal and/or pancreatic abnormalities, including sometimes severe hypocobalaminemia, when the endocrinopathy is initially diagnosed.7,8
Furthermore, all abnormalities detected should be treated concurrently to optimize clinical response to treatment. Many hyperthyroid cats are appropriately diagnosed and treated, but GI signs, especially weight loss, persist despite return to the euthyroid state. Subsequent evaluation of GI function as outlined above then reveals evidence of enteric disease and cobalamin deficiency. Only when these are also appropriately treated do the cats return to optimal health.
The diagnostic process
Determination of fecal fat (by percentage) would be desirable and may be the only way to confirm an intestinal problem in some patients. Fecal fat greater than 20% would indicate fat malabsorption. Unfortunately, such a test is not commercially available for pet cats. It has been reported that 100% of cats older than 7 years of age with serum tocopherol (vitamin E) less than 5 mg/L also have low fat digestibility, and that more than 90% of cats with serum cobalamin less than 100 g/L have low fat digestibility.3 So finding such low serum concentrations of either cobalamin or tocopherol can be the basis for inferring that a cat has low fat (and probably protein) digestibility.3
A new test that often reveals abnormalities in intestinal function in affected cats is an assay of fecal α1-proteinase inhibitor by species-specific immunoassay.9 This test is presently available only from the Gastrointestinal Laboratory at Texas A&M University. Abnormal results indicate the presence of an enteropathy-associated increase in enteric loss of protein; this test can detect protein-losing enteropathy that is not sufficiently severe to lower serum albumin (the liver can compensate for enteric protein loss). Chronic enteric protein loss can contribute to gradual depletion of lean body mass. In a recent study more than 70% of affected cats had abnormal [α1-PI] test results (Figure 7), but interestingly, serum albumin was slightly subnormal in only two of the 11 cats with protein-losing enteropathy.10
Figure 7. Fecal alpha1-proteinase inhibitor concentration was increased in 11 of 15 geriatric cats with idiopathic chronic enteropathy, indicating active protein-losing enteropathy in addition to the previously recognized nutrient malabsorption. The tan line indicates normal α1-PI concentration.
Finally, it should be noted that it is very common to see increased serum concentrations of trypsinlike immunoreactivity (fTLI) and/or pancreatic lipase (fPL) in these cats with idiopathic chronic enteropathy (Figure 8). The significance of these pancreatic abnormalities is not clear. Many affected cats show few if any signs that may be considered suggestive of pancreatitis (e.g.anorexia or vomiting), but the increases can be striking in some individuals.
Figure 8. Pancreatic pathology is also present in a high proportion of geriatric cats with idiopathic chronic enteropathy, as reflected in increased serum concentrations of trypsin-like immmunoreactivity (fTLI) and pancreatic lipase (fPL). The shaded areas represent normal reference ranges.
In the future, assay of enteric inflammatory markers such as fecal calprotectin may prove useful in confirming the presence of enteric disease, but the relationship of inflammation to this enteropathy is currently uncertain. Even histologic examination of intestinal biopsy specimens may not provide evidence of a conclusive diagnosis; lesions may be patchy and interpretation of biopsy findings is inherently subjective. It is also likely that in cats, as in dogs, functional problems in the intestine may not be associated with either inflammation or villous atrophy but rather with intraluminal microbial changes and biochemical derangements in the enterocytes lining the small intestine that are not revealed by classic histologic evaluation.
In some cats, despite a thorough investigation, it is not possible to confirm enteropathy. A presumptive diagnosis of idiopathic enteropathy is the best that can be achieved. The approach to management in these instances is essentially the same as for patients with histologically confirmed IBD — that is, a dietary change (low-carbohydrate alternative fiber source, novel antigen, or hydrolyzed diet), prebiotic or probiotic supplementation, correction of low serum cobalamin/folate concentrations, supplementation with vitamin E and perhaps other antioxidants, antibiotic treatment with metronidazole or tylosin, and perhaps glucocorticoid therapy or immunomodulation with chlorambucil or cyclosporine.11 However, in the absence of specific laboratory abnormalities or any overt clinical signs to monitor, other than perhaps very slowly progressive weight loss, it is probably premature to recommend particularly aggressive treatment for these patients. A cautious, conservative approach is warranted.
As many of the observations about digestive disturbances in elderly cats are relatively new, appropriate clinical studies evaluating treatment interventions have not been performed. Dietary changes and supplements would certainly be the safest and most easily administered interventions. When specific abnormalities such as hypocobalaminemia are identified, they should be rectified.
The effect of dietary changes has to be evaluated on an individual trial-and-error basis, which can be difficult if gradual weight loss is the only clinical sign to evaluate. Observing improvements in the newer GI disease markers, such as fecal α1-proteinase inhibitor and serum fPL, may provide objective evidence of a positive response, but the value of this approach remains to be evaluated.
Careful observation of stool characteristics may provide some evidence of improved digestibility, especially if grossly apparent abnormalities were present at the outset. If there is no apparent response to dietary change after two to four weeks, an alternative diet should be tried. I prefer to select diet changes based on reduced carbohydrate content (generally associated with increased protein content) or different amounts or types of fermentable fiber. Adjusting the fat content of the diet does not appear to be particularly useful in treating feline enteropathies. Unfortunately, definitive studies in geriatric cats with malabsorption have not been done. Treatment needs to be individualized and evaluated on a trial-and-error basis.
With regard to older cats in general, there is some evidence that diet can play a role in maintaining body weight and fat mass — and prolonging life. A control diet (nutritionally complete and balanced adult cat food) supplemented with antioxidants (vitamin E and ss-carotene), a blend of n-3 and n-6 fatty acids, and a prebiotic (dried chicory root) was associated with reduced decline in body weight and increased longevity (by more than 1 year) compared with feeding either the control diet alone or the control diet supplemented with antioxidants alone.6 These striking observations illustrate the potential benefit to be gained from dietary and other interventions to address the gastrointestinal changes that appear to be so common in aging cats.
1. Pittari J, Rodan I, Beekman G, et al. American Association of Feline Practitioners. Senior care guidelines. J Feline Med Surg 2009;11(9):763-778.
2. Caney S. Weight loss in the elderly cat. Appetite is fine, and everything looks normal…. J Feline Med Surg 2009;11(9):738-746.
3. Patil AR, Cupp CJ. Addressing age-related changes in feline digestion. Proc Nestle-Purina Compan Anim Nutr Summit, Focus Gastroenterol 2010:55-61.
4. Taylor EJ, Adams C, Neville R. Some nutritional aspects of aging cats and dogs.Proc Nutr Soc 1995;54:645-656.
5. Fahey GC, Barry KA, Swanson KS. Age-related changes in nutrient utilization by companion animals. Annu Rev Nutr 2008;28:425-445.
6. Cupp CJ, Kerr WW Effect of diet and body composition on life span in aging cats.Proc Nestle-Purina Compan Anim Nutr Summit Focus Gastroenterol 2010;36-42.
7. Steiner JM, Peterson MA, Ruaux CG, et al. Serum cobalamin and folate concentrations in cats with hyperthyroidism. J Vet Intern Med 2005;19:474-475.
8. Cook AK, Suchodolski JS, Steiner JM, et al. The prevalence of hypocobalaminaemia in cats with spontaneous hyperthyroidism. J Small Anim Pract 2011;52(2):101-106.
9. Burke KF, Broussard JD, Craig G, et al. Evaluation of fecal alpha1-proteinase inhibitor concentrations in cats with idiopathic inflammatory bowel disease and cats with gastrointestinal neoplasia. Vet J 2013;196(2)189-196.
10. Williams DA, Czarnecki-Maulden G. Protein-losing enteropathy commonly co-exists with high fecal fat output in geriatric cats with idiopathic malabsorption and persists following correction of subnormal serum cobalamin concentration. In Proc 23rd Congress Europ Coll Vet Inter Med - Comp Anim, Liverpool, England, Sept. 2013.
11. Webb CB. Feline inflammatory bowel disease. NAVC Clinician’s Brief 2012;10:11-14.
We are pleased to announce that an article, written by one of our very own members, Stephanie Bouchard, on EPI, was published in the August 2014 edition of the " Cat Fancy " magazine. It is an excellent article that brings much needed awareness to the general public about EPI. Check out Stephanie's blog:
Thank YOU Stephanie !!!!