Exocrine pancreatic insufficiency (EPI) is a malabsorptive syndrome caused by insufficient secretion of digestive enzymes from pancreatic acini. The most common causes of EPI in dogs and cats are pancreatic acinar atrophy and chronic pancreatitis. EPI is diagnosed by measurement of species-specific immunoassays for serum trypsin-like immunoreactivity, the concentration of which directly reflects the mass of functioning pancreatic acinar tissue. EPI is treated by pancreatic enzyme replacement therapy, nutritional management (low-residue diets with moderate fat content), and supplementation of cobalamin. Some dogs and cats have persistent clinical signs despite these treatments. Growing evidence suggests that these clinical signs may be due to enteric microbiota dysbiosis or the presence of concurrent diseases such as chronic enteropathies. Management of these abnormalities may improve outcome in dogs and cats with EPI. The long-term prognosis for dogs and cats with EPI is generally good if high-quality medical therapy is provided. Future studies are needed to further understand the causes of persistent dysbiosis in animals with EPI following initiation of pancreatic enzyme replacement therapy and assess the efficacy of treatments to ameliorate these abnormalities.
Pancreatitis commonly occurs in humans, dogs, and cats. For both veterinary and human health-care professionals, measurement of serum pancreatic lipase concentration or activity provides useful support for a diagnosis of pancreatitis. In this Currents in One Health manuscript, we will discuss commonly used lipase assays in veterinary medicine, namely catalytic colorimetric and immunological lipase assays. We highlight potential diagnostic pitfalls associated with analytical specificity, assay validation, and sample condition interferences. Catalytic lipase assays may detect extrapancreatic lipases. In addition, we propose a decision tree for interpretation of lipase assays in the context of a clinical patient.
(1) Determine if a relationship exists between ionized calcium (iCa) and pancreatic lipase (cPLI) concentration in dogs, and (2) assess for correlation between resolving hypercalcemia and cPLI concentrations in dogs after treatment for primary hyperparathyroidism (PHPT).
Phase I, 44 residual serum samples (collected April 2023) from client-owned dogs with a clinical indication for cPLI quantification. Phase II, 24 residual serum samples (collected August 2022 through February 2023) from client-owned dogs with PHPT pre- and postcorrection of hypercalcemia.
Serum cPLI and iCa concentrations were measured via the Spec cPL assay and a spectrophotometric method respectively. Spearman’s rank correlation coefficients were used to investigate if there was a correlation between serum calcium and cPLI concentrations. A paired t-test was used to investigate the effect of the resolution of hypercalcemia on serum cPLI concentrations.
Phase I, serum cPLI concentrations were negatively correlated with serum iCa concentrations (r = −.429, 95% CI [−.64, −.14], P = .005) in dogs with a clinical indication for cPLI quantification. Phase II, median serum cPLI concentrations were higher before (median: 228.5 μg/L, IQR: 351.3 μg/L) than after (median: 141.0 μg/L, interquartile ranges (IQR): 279.5 μg/L) management of hypercalcemia (PHPT model). However, the decrease in cPLI concentration was not statistically significant (P = .70).
Calcium depletion may result in an inverse relationship between serum cPLI and iCa concentrations in dogs with a clinical indication for cPLI quantification. Hypercalcemia may be associated with an above reference interval cPLI concentration in some dogs.
Lipases are water-soluble enzymes that hydrolyze water-insoluble lipid molecules, such as triglycerides, phospholipids, and galactolipids. They are ubiquitous in nature and are present in humans, animals, insects, plants, fungi, and microorganisms. While we commonly consider pancreatic lipase, this review provides an overview of several lipases that are important for the digestion and metabolism of lipids in veterinary species. All of these enzymes have specific functions but share a common α/β-hydrolase fold and a catalytic triad where substrate hydrolysis occurs. The pancreatic lipase gene family is one of the best characterized lipase gene families and consists of 7 mammalian subfamilies: pancreatic lipase, pancreatic lipase related proteins 1 and 2, hepatic lipase, lipoprotein lipase, endothelial lipase, and phosphatidylserine phospholipase A1. Other mammalian lipases that play integral roles in lipid digestion include carboxyl ester lipase and gastric lipase. Although most enzymes have preferred substrate specificity, much overlap occurs across the plethora of lipases because of the similarities in their structures. This has major implications for the development and clinical utilization of diagnostic assays. These implications are further explored in our companion Currents in One Health article by Lim et al in the August 2022 issue of the Journal of American Veterinary Medical Association, which focuses on pancreatic lipase assays for the diagnosis of pancreatitis.