Exocrine pancreatic insufficiency (EPI) is the inability to properly digest food due to a lack or reduction of
digestive enzymes made by the
pancreas. EPI can occur in humans and is prevalent in many conditions[1] such as
cystic fibrosis,[2]Shwachman–Diamond syndrome,[3] different types of
pancreatitis,[4] multiple types of diabetes mellitus (
Type 1 and
Type 2 diabetes),[5] advanced renal disease,[6] older adults,[7] celiac disease,[8] IBS-D,[9] IBD,[10] HIV,[11] alcohol-related liver disease,[12] Sjogren syndrome,[13] tobacco use,[14] and use of somatostatin analogues.[15]
EPI is caused by a progressive loss of the pancreatic cells that make digestive enzymes. Loss of digestive enzymes leads to
maldigestion and
malabsorption of nutrients from normal digestive processes. EPI can cause symptoms even before reaching the stages of malnutrition: 'mild' or 'moderate' EPI is when fecal elastase levels are <200 ug/g, whereas 'severe' EPI is considered to be when fecal elastase levels is <100 ug/g.[16]
The
exocrine pancreas is a portion of this organ that contains clusters of ducts (acini) producing
bicarbonate anion, a mild alkali, as well as an array of digestive enzymes that together empty by way of the interlobular and main pancreatic ducts into the
duodenum (upper small intestine).[17] The hormones
cholecystokinin and
secretin secreted by the stomach and duodenum in response to distension and the presence of food in turn stimulate the production of digestive enzymes by the exocrine pancreas.[18] The alkalization of the duodenum neutralizes the acidic
chyme produced by the stomach that is passing into it; the digestive enzymes serve to catalyze the breakdown of complex foodstuffs into smaller molecules for absorption and integration into metabolic pathways.[18] The enzymes include
proteases (
trypsinogen and
chymotrypsinogen), hydrolytic enzymes that cleave
lipids (the
lipasesphospholipase A2 and
lysophospholipase, and
cholesterol esterase), and
amylase to digest starches. EPI results from progressive failure in the exocrine function of the pancreas to provide its
digestive enzymes, often in response to a genetic condition or other disease state, resulting in the inability of the animal involved to properly digest food.[citation needed]
Signs and symptoms
Loss of pancreatic enzymes leads to maldigestion and malabsorption. Other symptoms may include:[19]
In humans, the most common causes of EPI are likely related to diabetes (10.5% global prevalence of diabetes,[20] with EPI rates of ranging from 30-50% in Type 1 and 20-30% of Type 2[21]) and IBS-D (7.6-10.8% global prevalence of IBS-D,[22] with EPI rates around 5-6%[9]). Other causes of EPI include
acute or
chronic pancreatitis and
cystic fibrosis, Crohn's disease, ulcerative colitis, celiac, advanced renal disease, older age, IBD, HIV, alcohol-related liver disease, Sjogren's syndrome, tobacco use, and use of somatostatin analogues.
EPI can also occur in 10-20% of the general population.[23][7][24]
Diagnosis
The three main tests used in considering a diagnosis of EPI are: fecal
elastase test, fecal fat test, and a direct pancreatic function test.[25] The latter is a less used test that assesses exocrine function in the pancreas by inserting a tube into the small intestine to collect pancreatic secretions.
The fecal elastase test is a less cumbersome test that has replaced the 72-hour fecal fat test; in the fecal elastase test, pancreatic enzyme replacement therapy (enzyme supplementation, the treatment for EPI) does not have to be stopped for or during fecal elastase testing.[26]
Treatment
EPI is treated with pancreatic enzyme replacement therapy (PERT) called
pancrelipase, which is used to break down fats (via a
lipase), proteins (via a
protease), and carbohydrates (via
amylase) into units that can be digested.[27] Pancrelipase is typically porcine derived in the prescription products although over-the-counter options also exist, including those made with plants and other non-porcine materials. In the US, there are 6 FDA-approved PERT products available on the market as of 2012.
Dosing can vary based on the need of the individual.[28] PERT is considered to be safe, effective, and tolerable for people with EPI regardless of the cause of EPI.[29]
In addition, various nutrient deficiencies that can be caused by EPI need to be evaluated, tested, and treated. The impact of nutrient deficiencies on the body's metabolic pathways, muscle tissue, bone density, organs, and overall health can cause a wide range of often misdiagnosed symptoms for those impacted by exocrine pancreatic insufficiency.[30]
Other animals
EPI also occurs in
dogs and other animals.
Chronic pancreatitis is the most common cause of EPI in
cats. In dogs, the most common cause is pancreatic acinar atrophy, arising as a result of
genetic conditions, a blocked
pancreatic duct, or prior infection.
In animals, signs of EPI are not present until 85 to 90 percent of the pancreas is unable to secrete its enzymes.[32] In dogs, symptoms include weight loss, poor hair coat,
flatulence, increased appetite,
coprophagia, and diarrhea. Feces are often yellow-gray in color with an oily texture. There are many concurrent diseases that mimic EPI, and severe pancreatitis is one that if allowed to continue unabated can lead to EPI.[citation needed]
Diagnosis and treatment
The most reliable test for EPI in dogs and cats is serum trypsin-like immunoreactivity (TLI);[38] a low value indicates EPI. Fecal
elastase levels may also be used for diagnosis in dogs.[39]
In dogs, the best treatment is to supplement the animals' food with dried pancreatic extracts. There are commercial preparations available, but chopped bovine pancreas from the butcher can also be used. (Pork pancreas should not be used because of the rare transmission of
pseudorabies).[40] Symptoms usually improve within a few days, but lifelong treatment is required to manage the condition. A rare side-effect of use of dried pancreatic extracts is
oral ulceration and bleeding.[41]
Because of malabsorption, serum levels of
cyanocobalamin (vitamin B12) and
tocopherol (vitamin E) may be low. These may be supplemented, although since cyanocobalamin contains the toxic chemical
cyanide, dogs that have serious cobalamin issues should instead be treated with
hydroxocobalamin or
methylcobalamin.[citation needed]
Cyanocobalamin deficiency is very common in cats with EPI because about 99 percent of
intrinsic factor (which is required for cyanocobalamin absorption from the intestine) is secreted by the pancreas. In dogs, this figure is about 90 percent, and only about 50 percent of dogs have this deficiency.[40]
Cats may suffer from
Vitamin K deficiencies. If there is
bacterial overgrowth in the intestine, antibiotics should be used, especially if treatment is not working.
In dogs failing to gain weight or continuing to show symptoms, modifying the diet to make it low-fiber and highly digestible may help. Despite previous belief that low-fat diets are beneficial in dogs with EPI, more recent studies have shown that a high-fat diet may increase absorption of nutrients and better manage the disease.[42] However, it has been shown that different dogs respond to different dietary modifications, so the best diet must be determined on a case-by-case basis.[43]
One possible
sequela,
volvulus (mesenteric torsion), is a rare consequence of EPI in dogs.[32]
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