Exocrine pancreatic insufficiency
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]
Exocrine pancreatic insufficiency
Diabetes (Type 2), Type 1 Diabetes, Pancreatitis, Celiac, Cystic Fibrosis, IBS-D, IBD, somatostatin analogues
older age, tobacco use, alcohol use
Fecal elastase test
pancreatic enzyme replacement therapy (PERT)
pancrelipase
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 lipases phospholipase 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.
Loss of pancreatic enzymes leads to maldigestion and malabsorption. Other symptoms may include:[19]
Causes[edit]
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[edit]
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[edit]
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]