Clinical Overview

What is Exocrine Pancreatic Insufficiency (EPI)?

EPI is a condition characterized by the deficiency of exocrine pancreatic enzymes below the threshold required for normal digestion and is associated with morbidity and reduced quality of life.^1,2

Physiology of the Pancreas

The pancreas is a dual-function gland with:

Exocrine Function Plays a pivotal role in digestive physiology by synthesizing and releasing digestive enzymes into the duodenum:

Lipase

Breaks down ester bonds of lipids and fats into fatty acids and glycerol
Deficiency in lipase causes fat-soluble vitamin deficiencies (vitamins A, D, E, K)

Protease

Protease
(trypsin, chymotrypsin)

Breaks down protein into peptides and amino acids

Amylase

Breaks carbohydrates (starches) into dextrins and simple sugars like glucose

Contributes significantly to nutrient metabolism and overall nutritional well-being⁴

Endocrine Function Plays a crucial role in glucose homeostasis³ by producing and releasing hormones into the bloodstream:

Insulin

Lowers blood glucose levels by facilitating cellular glucose update
Promotes glycogenesis in the liver and muscle tissue by converting glucose to glycogen
Inhibits lipolysis (fat breakdown) and stimulates lipogenesis (fat storage) in adipose tissue

Glucagon

Increases plasma glucose concentration by stimulating hepatic glycogenolysis (glycogen breakdown) and gluconeogenesis (glucose synthesis from noncarbohydrate sources)
Opposes the action of insulin to ensure stable blood glucose levels

Somatostatin

Inhibits endocrine secretion, particularly insulin and glucagon, thus modulating glucose homeostasis
Reduces gastrointestinal motility and delays gastric emptying, impacting nutrient absorption
Modulates the secretion of other hormones like growth hormone and thyroid-stimulating hormone

Pancreatic
polypeptides

Pancreatic Polypeptides

Modulates exocrine pancreatic function, inhibiting enzyme secretion and bicarbonate production
Regulates gastrointestinal motility and may influence satiety and energy balance
Influences food intake and energy homeostasis, possibly reducing appetite

Pathophysiology

In individuals affected with EPI there is a reduction in pancreatic enzyme production, delivery and/or activity to a level below the threshold required to maintain normal digestion.¹

Decreased production of pancreatic enzymes due to loss of pancreatic parenchyma or decreased endogenous neurohormonal stimulation²

Decreased Production²

Loss of pancreatic parenchyma

Impaired hormonal stimulation

Decreased delivery of pancreatic enzymes and bicarbonate due to pancreatic duct obstruction²

Decreased Delivery²

Pancreatic duct obstruction

Impaired activity of pancreatic enzymes driven by inactivation of pancreatic enzymes due to low duodenal pH and decreased activation of proenzyme caused by asynchrony of gastric emptying and pancreatic secretion; or impaired interaction with chyme and biliary salts^2,5*

Decreased Activity²*

Poor mixing of pancreatic
enzymes, postprandial
asynchrony, low duodenal pH

This inadequacy impairs the effective digestion of dietary carbohydrates, fats, and proteins in the small intestine.¹ When partially digested food reaches the colon, it may produce symptoms such as osmotic diarrhea and steatorrhea.⁶

Abdominal pain/discomfort, flatulence, and bloating can also arise partly due to bacterial fermentation, which converts undigested nutrients to short-chain fatty acids for energy.^6-8

Take an immersive journey into the physiology of the
exocrine pancreas and the pathophysiology of EPI.

How Does EPI Manifest?

Clinical features of EPI are usually nonspecific and can include:⁹

Abdominal pain/discomfort

Diarrhea

Unexplained weight loss

Steatorrhea

Bloating

Flatulence

What Are the Clinical Manifestations of EPI?

Malabsorption and nutritional deficiencies can reduce quality of life and increase the risk of:^1,10-12

Osteoporosis, osteopenia, and bone fractures¹¹

Sarcopenia¹³

Cardiovascular risk¹⁴

Mortality¹⁵

Watch this video to see the clinical consequences of EPI

Underlying Conditions and Procedures

Any disease that significantly damages the pancreatic tissue can cause EPI. In addition, EPI can be a consequence of secondarily impaired exocrine pancreatic function.

EPI often results from damage or decreased signaling to the pancreas from diseases such as:

Acute pancreatitis

Celiac disease

Chronic pancreatitis

Crohn’s disease

Cystic fibrosis

Pancreatic cancer

Type 1 diabetes

Type 2 diabetes

Surgical procedures of the pancreas or digestive tract may also cause EPI:

Gastric surgery

Pancreatectomy

BACK TO Home

CONTINUE TO Diagnosing EPI

References: 1. Lindkvist B. World J Gastroenterol. 2013;19(42):7258-7266. doi:10.3748/wjg.v19.i42.7258 2. Othman MO et al. Int J Clin Pract. 2018;72(2):e13066. doi:10.1111/ijcp.13066 3. El Sayed SA, Mukherjee S. Physiology, Pancreas. In: StatPearls. Treasure Island (FL): StatPearls Publishing; May 1, 2023. 4. Atkinson MA et al. Diabetologia. 2020;63(10):1966-1973. doi:10.1007/s00125-020-05203-7 5. Sikkens EC et al. Best Pract Res Clin Gastroenterol. 2010;24(3):337-347. doi:10.1016/j.bpg.2010.03.006 6. Whitcomb DC et al. Gastroenterology. 2023;165(5):1292-1301. doi:10.1053/j.gastro.2023.07.007 7. Keller J et al. Gut. 2005;54 Suppl 6(Suppl 6):vi1-vi28. doi:10.1136/gut.2005.065946 8. Owira PM et al. JPEN J Parenter Enteral Nutr. 2008;32(1):63-71. doi:10.1177/014860710803200163 9. Alkaade S et al. Am J Manag Care. 2017;23(12)(suppl):S203-S209. 10. Pezzilli R et al. World J Gastroenterol. 2013;19(44):7930-7946. doi:10.3748/wjg.v19.i44.7930 11. Sikkens ECM et al. J Clin Gastroenterol. 2014;48(5):e43-e46. doi:10.1097/MCG.0b013e31829f56e7 12. Sikkens EC et al. Pancreatology. 2013;13(3):238-242. doi:10.1016/j.pan.2013.02.008 13. Shintakuya R et al. Pancreatology. 2017;17(1):70-75. doi:10.1016/j.pan.2016.10.005 14. de la Iglesia D et al. J Gastroenterol Hepatol. 2019;34(1):277-283. doi:10.1111/jgh.14460 15. de la Iglesia D et al. J Clin Gastroenterol. 2018;52(8):e63-e72. doi:10.1097/MCG.0000000000000917

Pancreatic cancer is the third most common cause of deaths due to cancer in the United States. Only 20% of cases are resectable at the time of diagnosis. Even after surgical resection, the 5-year overall survival is still poor (20%).^1,2

Epidemiology

It was estimated in 2023 that there would be 64,050 new cases of pancreatic cancer in the United States, which is currently the third leading cause of cancer-related death.³

with unresectable pancreatic cancer have EPI^4,5

with resectable pancreatic cancer have EPI^6,7

Pathophysiology

There are multiple potential mechanisms underlying EPI in pancreatic cancer.

The degree of EPI in patients following pancreatic resection is impacted by:

Type of surgery⁸
Extent of remaining pancreatic tissue⁹

In patients with unresectable pancreatic cancer, mechanisms contributing to EPI may include:

Pancreatic duct obstruction⁸
Pancreatic atrophy secondary to duct obstruction and fibrosis^8-10
Ongoing destruction of pancreatic parenchyma by the tumor^8,11

Signs such as weight loss in pancreatic cancer is highly prevalent, with 71.5% of patients with pancreatic ductal adenocarcinoma presenting with >5% weight loss at time of diagnosis.¹²

Recognize the onset of other conditions and deficiencies in pancreatic cancer patients with EPI.

*55% and 89% were based on using FE-1 <200 Î¼g /g and CFA <93% as evidence for EPI, respectively. CFA=coefficient of fat absorption; EPI=exocrine pancreatic insufficiency.
References: 1. Puckett Y, Garfield K. Pancreatic Cancer. StatPearls Publishing; 2023. Updated September 26, 2022. Available from: https://www.ncbi.nlm.nih.gov/books/NBK518996/ 2. Tamburrino D et al. World J Gastroenterol. 2014;20(32):11210-11215. doi:10.3748/wjg.v20.i32.11210 3. Cancer Stat Facts: Pancreatic Cancer. National Cancer Institute. Accessed February 8, 2024. https://seer.cancer.gov/statfacts/html/pancreas.html 4. Partelli S et al. Dig Liver Dis. 2012;44(11):945-951. doi:10.1016/j.dld.2012.05.017 5. Sikkens ECM et al. J Clin Gastroenterol. 2014;48(5):e43-e46. doi:10.1097/MCG.0b013e31829f56e7 6. Belyaev O et al. Langenbecks Arch Surg. 2013;398(4):547-555. 7. Lim JH et al. HPB (Oxford). 2017;19(5):388-395. 8. Papadoniou N et al. Anticancer Res. 2008;28(1B):543-549. 9. Bartel MJ et al. Dig Liver Dis. 2015;47(12):1013-1020. 10. Phillips ME. Pancreatology. 2015;15(5):449-455. 11. Partelli S et al. Dig Liver Dis. 2012;44(11):945-951. 12. Nemer L et al. Pancreas. 2017;46(9):1152-1157. doi:10.1097/MPA.0000000000000898

This autosomal recessive disease results from mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. It affects multiple organ systems, with most devastating effects on the lungs. Individuals with this disease are at risk of developing chronic pulmonary infections and EPI, among other complications.¹

Epidemiology

Approximately 30,000 individuals in the United States are affected with CF, of which up to 90% develop EPI.²

EPI leads to poor absorption of fat-soluble vitamins, macronutrients, and essential fatty acids. This results in malnutrition and confers a burden on individuals with CF, as nutritional deficiencies are associated with clinical manifestations that may significantly affect their health.^3-5

Pathophysiology

Mechanism underlying EPI in CF:^6-11

CF=cystic fibrosis; EPI=exocrine pancreatic insufficiency.
References: 1. Ratjen F et al. Nat Rev Dis Primers. 2015;1:15010. doi:10.1038/nrdp.2015.10 2. Cystic Fibrosis Foundation Patient Registry. 2018 Patient Registry Annual Data Report 2018; 2019. 3. Yen EH. J Pediatr. 2013;162(3):530-535. doi:10.1016/j.jpeds.2012.08.040 4. Solomon M. Clin Chest Med. 2016;37(1):97-107. doi:10.1016/j.ccm.2015.11.009 5. Schindler T. Nutr Clin Pract. 2015;30(4):488-500. doi:10.1177/0884533615591604 6. Pallagi P. Pancreas. 2015;44(8):1211-1233. doi:10.1097/MPA.0000000000000421 7. Bardeesy N. Nat Rev Cancer. 2002;2:897-909. doi:10.1038/nrc949 8. Culhane S. Nutr Clin Pract. 2013;28(6):676-683. doi:10.1177/0884533613507086 9. Sathe MN. Pediatr Clin North Am. 2016;63(4):679-98. doi:10.1016/j.pcl.2016.04.008 10. Stevens T. Am J Gastroenterol. 2004;99(11):2256-2270. doi:10.1111/j.1572-0241.2004.40694.x 11. Borowitz D. J Pediatr Gastroenterol Nutr. 2005;41(3):273-85. doi:10.1097/01.mpg.0000178439.64675.8d

This surgical procedure is commonly associated with EPI, among other gastrointestinal complications such as dumping syndrome, delayed gastric emptying, malnutrition, and small intestinal bacterial overgrowth. Furthermore, pancreatectomy can lead to clinical sequelae such as diabetes, fatty liver, and bone disease.^1-7

Epidemiology

The incidence of EPI varies by surgical technique.

Pancreaticoduodenectomy

A majority of studies have shown that >60% of patients with chronic pancreatitis develop EPI after the procedure , and the incidence of EPI increases to 64%-100% with malignancy⁸

Distal pancreatectomy

EPI develops in 27.5%-63% of patients with chronic pancreatitis after the procedure⁸

Central pancreatectomy

The rate of developing EPI after the procedure is approximately 10%⁸

Total pancreatectomy

43.5% of patients who have had a total pancreatectomy experienced symptoms of exocrine insufficiency⁹

Pathophysiology

Potential mechanisms underlying EPI in patients who underwent pancreatectomy include:^3,10

Alteration of pancreatic anatomy
Fibrosis present in remaining pancreatic remnant
Extensive denervation following lymph node dissection
Reduction of glandular tissue

Learn about gastrointestinal complications that can occur in post-pancreatic surgery patients.

EPI=exocrine pancreatic insufficiency.
References: 1. Berry AJ. Nutr Clin Pract. 2013;28(3):330-357. doi:10.1177/0884533612470845 2. Pappas S et al. Nutr Clin Pract. 2010;25(3):234-243. doi:10.1177/0884533610368709 3. Lindkvist B. World J Gastroenterol. 2013;19(42):7258-7266. doi:10.3748/wjg.v19.i42.7258 4. Pezzilli R et al. World J Gastroenterol. 2013;19(44):7930-7946. doi:10.3748/wjg.v19.i44.7930 5. Decher N, Berry A. Pract Gastroenterol. 2012;36(8):30-42. 6. Muniz CK et al. Pancreas. 2014;43(3):445-450. doi:10.1097/MPA.0000000000000048 7. Petzel MQB, Hoffman L. Nutr Clin Pract. 2017;32(5):588-598. doi:10.1177/0884533617722929 8. Sabater L et al. Ann Surg. 2016;264(6):949-958. doi:10.1097/SLA.0000000000001732 9. Scholten L et al. Br J Surg. 2019;106(13):1735-1746. doi:10.1002/bjs.11296 10. Bartel MJ et al. Dig Liver Dis. 2015;47(12):1013-1020. doi:10.1016/j.dld.2015.06.015

Gastric surgery, which involves modifying the digestive system, may be performed for various reasons, including gastroesophageal reflux disease, stomach cancer, peptic ulcer disease, gastroparesis, and duodenal bypass. Bariatric surgery, a type of gastric surgery performed to address severe obesity, represents a substantial proportion of these interventions.

Epidemiology

The number of bariatric surgeries in the United States are increasing, with 280,000 cases in 2022.¹

who underwent Roux-en-Y gastric bypass have EPI.²* There is a low likelihood of developing EPI with gastric banding.¹

who underwent gastric surgery develop EPI,³ with increased incidence in cases of total gastrectomy, duodenal bypass procedures, and vagal denervation.^3,4

Pathophysiology

Potential mechanisms uderlying EPI in patients who underwent gastric surgery include:⁵

Altered gastric relaxation due to the absence of neural gastric reflexes
Absence of neural gastric stimulation responsible for pancreatic secretion
Rapid gastric emptying and asynchrony between gastric emptying and biliopancreatic secretion
Extensive denervation of the pancreas due to lymph node dissection and truncal vagotomy

Common Gastric Procedures¹

Gastric bypass (RYGB)

Adjustable gastric band

Sleeve gastrectomy

Biliopancreatic diversion with duodenal switch

*Prevalence data in patients who underwent distal or proximal RYGB. EPI=exocrine pancreatic insufficiency; RYBG=Roux-en-Y gastric bypass.
References: 1. Clapp B et al. PubMed. 2024;20(5):425-431. doi:10.1016/j.soard.2024.01.012 2. Borbély Y et al. Surg Obes Relat Dis. 2016;12(4):790-794. doi:10.1016/j.soard.2015.10.084 3. Lee AHH, Ward SM. J Pancreas. 2019;20(5):130-137. 4. Capurso G et al. Clin Exp Gastroenterol. 2019;12:129-139. doi:10.2147/CEG.S168266 5. Antonini F et al. Dig Liver Dis. 2018;50(1):1-5. doi:10.1016/j.dld.2017.10.025

This metabolic disorder is characterized by hyperglycemia due to insulin resistance and/or impaired β cell function.^1,2 T2DM most often develops in ages >45 years, but it is appearing more frequently in children, teens, and young adults.³

Epidemiology

Of the >37 million individuals with diabetes in the United States, approximately 90%-95% have T2DM.³

with T2DM have EPI (using FE-1 <200 µg/g as evidence for EPI)^4,5

Pathophysiology

While the exact mechanisms of exocrine dysfunction in T2DM are unclear, there are multiple potential mechanisms including:⁵

*Only 0.9% of patients with T2DM were found to have autoantibodies against exocrine antigens vs up to 39% of patients with T1DM.⁶ Image adapted from: Radlinger B, et al. Curr Diab Rep. 2020;20(6):18. EPI=exocrine pancreatic insufficiency; T2DM=Type 2 diabetes.
References: 1. Singh VK et al. World J Gastroenterol. 2017;23(39):7059-7076. doi:10.3748/wjg.v23.i39.7059 2. Atkinson MA et al. Diabetologia. 2020;63(10):1966-1973. doi:10.4158/ EP-2020-0295 3. Type 2 diabetes. Centers for Disease Control and Prevention. Updated April 18, 2023. Accessed February 7, 2024. https://www.cdc.gov/diabetes/basics/type2.html 4. Mohapatra S et al. Pancreas. 2016;45(8):1104-1110. doi:10.1097/MPA.0000000000000609 5. Zhang J et al. Int J Endocrinol. 2022;2022:7764963. doi: 10.1155/2022/7764963 6. Radlinger B et al. Curr Diab Rep. 2020;20(6):18. doi:10.1007/s11892-020-01304-0

As an autoimmune disease, T1DM is characterized by immune-mediated destruction of islet cells, leading to deficiency in insulin production. It typically has an early onset.^1,2

Epidemiology

In 2019, approximately 2 million people in the United States had T1DM, including nearly 304,000 children and adolescents.³

with T1DM have EPI (using FE-1 <200 µg/g as evidence for EPI)⁴

Pathophysiology

While the exact mechanisms of exocrine dysfunction in T1DM are unclear, there are multiple potential mechanisms including:^1,5,6

*Only 0.9% of patients with T2DM were found to have autoantibodies against exocrine antigens vs up to 39% of patients with T1DM.⁶ Image adapted from: Radlinger B, et al. Curr Diab Rep. 2020;20(6):18. EPI=exocrine pancreatic insufficiency;T1DM=Type 1 diabetes.
References: 1. Singh VK et al. World J Gastroenterol. 2017;23(39):7059-7076. doi:10.3748/wjg.v23.i39.7059 2. Ewald N, Hardt PD. World J Gastroenterol. 2013;19(42):7276-7281. doi:10.1155/2011/761950 3. Statistics about diabetes. American Diabetes Association. Updated November 2, 2023. Accessed February 7, 2024. https://diabetes.org/about-diabetes/ statistics/about-diabetes 4. Mohapatra S et al. Pancreas. 2016;45(8):1104-1110. doi:10.1097/MPA.0000000000000609 5. Zhang J et al. Int J Endocrinol. 2022;2022:7764963. doi:10.1155/2022/7764963 6. Radlinger B et al. Curr Diab Rep. 2020;20(6):18. doi:10.1007/s11892-020-01304-0

As an inflammatory bowel disease, Crohn’s disease commonly affects the small bowel, and particularly the terminal ileum. However, it can affect any part of the gastrointestinal tract.¹ The course of this disease is progressive and destructive, and is characterized by relapse and remissions.^1,2

Epidemiology

Up to 780,000 individuals in the United States have Crohn’s disease.³

with Crohn’s disease have EPI (using FE-1 <200 µg/g as evidence for EPI)⁴

Risk Factors for EPI in Crohn’s Disease

Patients have an increased risk of developing EPI if they are experiencing ≥3 bowel movements per day, loose stools, and have a history of surgery.⁴

Pathophysiology

Potential mechanisms underlying EPI in Crohn’s disease include:^4,5

Underlying pancreatitis due to presence pancreatic autoantibodies or treatment-related effects from IBD treatments (e.g., thiopurines, aminosalicylates, corticosteroids, intralipids)
Duodenal reflux secondary to inflammation causing damage to the pancreatic duct
Reduced intestinal hormone secretion due to scarring/ inflammation resulting in insufficient stimulation of the pancreas

Crohn’s disease most commonly occurs in the small intestine and colon, causing inflammation and damage to the GI tract.³

EPI=exocrine pancreatic insufficiency; IBD=inflammatory bowel disease.
References: 1. Ranasinghe IR, Hsu R. Crohn Disease. StatPearls Publishing; 2023. Feb 20, 2023. Available from: https://www.ncbi.nlm.nih.gov/books/NBK436021/ 2. Roda G et al. Crohn’s disease. Nat Rev Dis Primers. 2020;6(1):22. doi:10.1038/s41572-020-0156-2 3. The facts about inflammatory bowel diseases. Crohn’s & Colitis Foundation. November 2014. Accessed February 7, 2024. https://www.crohnscolitisfoundation.org/sites/default/files/legacy/assets/pdfs/ibdfactbook.pdf 4. Singh VK et al. World J Gastroenterol. 2017;23(39):7059-7076. doi:10.3748/wjg.v23.i39.7059 5. Srinath AI et al. Inflamm Bowel Dis. 2016;22(2):465-475.

With this immune-mediated disorder, exposure to gluten causes inflammation with crypt hyperplasia and villous atrophy of the small intestine. Hence, individuals with celiac disease should adhere to a gluten-free diet. It may also involve extraintestinal complications such as acute pancreatitis.¹

Epidemiology

This condition is prevalent in nearly 1% of adults in the United States and Europe.^1,2 Prevalence of EPI in celiac disease depends on whether patient is on a gluten-free diet.^3,4 The American College of Gastroenterology clinical guidelines recommend that patients with nonresponsive celiac disease should be evaluated for EPI.⁵

with untreated celiac disease have EPI⁶

who are on a gluten-free diet have EPI^3,6

with celiac disease not responding to a gluten-free diet have EPI³

Pathophysiology

Potential mechanisms underlying EPI in untreated celiac disease include:^6-8

Impaired intestinal hormonal stimulation of the pancreas
- Impaired synthesis, storage, and release of secretagogues (i.e., CCK and secretin)
- Defective postprandial response (CCK stimulation) due to intestinal inflammation and mucosal villous atrophy
Substantially impaired exocrine pancreatic function may be caused by comorbid chronic pancreatitis
Protein malnutrition, potentially due to untreated malabsorption, is associated with decreased pancreatic enzyme secretion and pancreatic structural changes

The small intestine villi of a celiac patient (pictured on the right) are damaged, resulting in malabsorption.

Watch this video on the etiology and pathophysiology of celiac disease.

CCK=cholecystokinin; EPI=exocrine pancreatic insufficiency.
References: 1. Ludvigsson JF et al. Clin Gastroenterol Hepatol. 2007;5(11):1347-1353. 2. Evans KE et al. Dig Dis Sci. 2010;55(10):2999-3004. doi:10.1007/s10620-010-1261-y 3. Leeds JS et al. Aliment Pharmacol Ther. 2007;25(3):265-71. doi:10.1111/j.1365-2036.2006.03206.x 4. Vujasinovic M et al. Postgrad Med J. 2015;91(1079):497-500. doi:10.1136/postgradmedj-2015 -133262 5. Rubio-Tapia A et al. Am J Gastroenterol. 2013;108(5):656-676. doi:10.1038/ajg.2013.79 6. Singh VK et al. World J Gastroenterol. 2017;23(39):7059-7076. doi:10.3748/ wjg.v23.i39.7059 7. Capurso G et al. Clin Exp Gastroenterol. 2019;12:129-139. doi:10.2147/CEG.S168266 8. Pezzilli R et al. World J Gastroenterol. 2013;19(44):7930-7946. doi:10.3748/ wjg.v19.i44.7930

CP is a pathological, proinflammatory condition of the pancreas observed in individuals who exhibit persistent pathological responses to parenchymal injury and stress. Those affected by this disease likely have genetic (e.g., hereditary conditions: PRSSI, SPINK1, CFTR), environmental (smoking, alcohol consumption, high-fat diets, poor nutrition) and/or other risk factors (e.g., certain medications, autoimmune disorders) that contribute to its development.¹

Epidemiology

The prevalence of CP is 98.7 per 100,000 persons per year.² 30%-90% of patients with CP develop EPI.³ CP secondary to alcohol use is associated with higher cumulative incidence of EPI.³

Pathophysiology

Potential mechanisms underlying EPI in CP include:³

Reduction in pancreatic enzyme due to destruction of pancreatic parenchyma
Decrease in delivery of pancreatic enzymes and bicarbonate secondary to pancreatic duct obstruction

Hear from gastroenterologists as they share insights on diagnosing EPI in CP through Patient Cases

CP=chronic pancreatitis; EPI=exocrine pancreatic insufficiency.
References: 1. Whitcomb DC et al. Pancreatology. 2016;16(2):218-224. doi:10.1016/j.pan.2016.02.001 2. Machicado JD et al. Pancreatology. 2019;19(6):813-818. doi:10.1016/ j.pan.2019.07.003 3. Kempeneers MA et al. Pancreas. 2020;49(2):242-248. doi:10.1097/MPA.0000000000001473

This inflammatory condition of the pancreas has many causes, with gallstones and alcohol abuse being among the most common.¹ The severity of AP ranges from mild and self-resolving to severe with complications.^1,2

Epidemiology

From 2001-2014, the rate of AP increased from 65.38 to 81.88 per 100,000 U.S. adults per year.³ Prevalence of EPI in AP depends on its severity.^4,5

with moderate or severe AP develop EPI^5,6

with mild AP episodes develop EPI^5,6

Risk Factors for EPI in AP^5-7

Recurrence of AP
Severity of AP
Alcoholic etiology
History of necrosectomy

Pathophysiology

Potential mechanisms underlying EPI in AP include:⁵

Ductal obstruction resulting from inflammation
Secondary impairment of hormonal mediators (CCK and secretin)
Damaged receptors controlling enzyme-releasing acinar cells
Diminished pancreatic function due to necrosis or surgical removal of necrosis

Case Study Review: Risk Factors of EPI in AP

AP=acute pancreatitis; CCK=cholecystokinin; EPI=exocrine pancreatic insufficiency.
References: 1. Wang GJ et al. World J Gastroenterol. 2009;15(12):1427-1430. doi:10.3748/wjg.15.1427 2. Gapp J, Tariq A, Chandra S. Acute Pancreatitis. StatPearls Publishing; 2023. Updated February 9, 2023. Available from: https://www.ncbi.nlm.nih.gov/books/NBK482468/ 3. Gapp J et al. Pancreas. 2019;48(4):548-554. doi:10.1097/MPA.0000000000001275 4. Peery AF et al. Gastroenterology. 2012;143(5):1179-1187. doi:10.1053/j.gastro.2012.08.002 5. Hollemans RA et al. Pancreatology. 2018;18(3):253-262. doi:10.1016/j.pan.2018.02.009 6. Huang W et al. Dig Dis Sci. 2019;64(7):1985-2005. doi:10.1007/s10620-019-05568-9 7. Capurso G et al. Clin Exp Gastroenterol. 2019;12:129-139. doi:10.2147/CEG.S168266

Exocrine Cells

Acinar cells^1,2

Comprise ~85% of the pancreas and secrete pancreatic enzymes

Amylase, protease, and lipase

Ductal cells^3-6

Secrete alkaline solution
Neutralizes stomach acid
Protects pancreatic enzymes
Prevents bile salt precipitation
Promotes micelle formation
Helps maintain microbial balance

Endocrine Cells

Langerhans Islet cells³

Comprise ~2% of the pancreas and secrete pancreatic hormones
Composed of at least four types of cells, including alpha, beta, delta, and PP cells, which secrete glucagon, insulin, somatostatin and pancreatic polypeptide, respectively

References: 1. Afroze S et al. Ann Transl Med. 2013;1(3):29. doi:10.3978/j.issn.2305-5839.2012.12.01 2. Konturek SJ et al. J Physiol Pharmacol. 2003;54(3):293-317. 3. Martini FH et al. Fundamentals of Anatomy & Physiology. 9th ed. Benjamin Cummings; 2012:862-915. 4. Hall JE, Guyton AC. Guyton and Hall Textbook of Medical Physiology. 12th ed. Saunders Elsevier; 2011:789-798. 5. Sikkens EC et al. Best Pract Res Clin Gastroenterol. 2010;24(3):337-347. doi:10.1016/j.bpg.2010.03.006 6. Chandra R et al. Curr Opin Gastroenterol. 2009;25(5):441-446. doi:10.1097/MOG.0b013e32832e9c41

Clinical Overview

What is Exocrine Pancreatic Insufficiency (EPI)?

Physiology of the Pancreas

Pathophysiology

Decreased Production2

Decreased Delivery2

Decreased Activity2*

Take an immersive journey into the physiology of the exocrine pancreas and the pathophysiology of EPI.

How Does EPI Manifest?

Clinical features of EPI are usually nonspecific and can include:9

What Are the Clinical Manifestations of EPI?

Watch this video to see the clinical consequences of EPI

Underlying Conditions and Procedures

EPI often results from damage or decreased signaling to the pancreas from diseases such as:

Surgical procedures of the pancreas or digestive tract may also cause EPI:

You are now leaving the Essentials of EPI website.

Decreased Production²

Decreased Delivery²

Decreased Activity²*

Take an immersive journey into the physiology of the
exocrine pancreas and the pathophysiology of EPI.

Clinical features of EPI are usually nonspecific and can include:⁹