EPI can result from various underlying causes1

Examining the role of the pancreas in digestion can help clarify EPI's etiology. EPI is caused by inadequate production, delivery, or activity of the pancreatic enzymes needed for digestion.

The pancreas has two roles within the body

Diagram of an enzyme within the pancreas

85% exocrine (acinar and duct tissue)2-4:

  • Acinar cells synthesize, store, and secrete digestive enzymes such as lipase, protease, and amylase into the duodenum
  • Ductal cells secrete NaHCO3 and water, which neutralizes the acidic pH of food, and helps carry the digestive enzymes into the duodenum
Diagram of the pancreas inadequately producing the pancreatic enzymes needed for normal digestion

2% endocrine (islets of Langerhans)2,5:

  • The islets of Langerhans release pancreatic hormones such as glucagon, insulin, somatostatin, and pancreatic polypeptide
  • These hormones are secreted directly into the bloodstream and help control glucose levels

The pancreatic digestive enzymes

The major hormonal stimulus that causes pancreatic digestive enzyme secretion is the release of cholecystokinin (CCK) from the duodenum.6-8

The pancreatic enzymes are comprised of7:

  • LIPASE - breaks down fats into fatty acids
  • PROTEASE - breaks down proteins into amino acids
  • AMYLASE - breaks down carbohydrates into simple sugars

Bicarbonate alkalinizes intraluminal duodenal pH and prevents inactivation of the enzymes. When nutrients arrive in the proximal small bowel, the pancreatic enzymes begin to break them down.6,7

Digestion and absorption of nutrients is dependent on normal pancreatic enzyme secretion and function6

Normal pancreatic enzyme secretion varies with content and volume of meal ingested.9

Normal pancreatic enzyme secretion9
(lipase units per meal)

480,000
720,000
(average)
960,000

Normal digestion also depends on postprandial synchrony between delivery of nutrients to the duodenum and discharge of pancreatic enzymes.9

EPI is caused by inadequate production, delivery, or activity of pancreatic enzymes needed for normal digestion1

Diagram of the pancreas inadequately producing the pancreatic enyzmes needed for normal digestion
EPI may result in:

MALDIGESTION10

EPI leads to an inability to digest food properly, with fat maldigestion being the most profound.

MALABSORPTION10

Malabsorption of fat soluble vitamins A, D, E, and K may accompany EPI.

MALNUTRITION11,12

EPI-related maldigestion and malabsorption can lead to malnutrition and weight loss.

GASTROINTESTINAL (GI) SYMPTOMS7,11,13,14

EPI can lead to GI symptoms due to undigested and unabsorbed food. Steatorrhea, the classic clinical sign of EPI, may not occur until the disease is advanced. Yet, there may be significant maldigestion and malabsorption without overt steatorrhea.

EPI is caused by inadequate production, delivery, or activity of the pancreatic enzymes needed for digestion1

This can result from a defect in the pancreatic parenchyma or a decrease in enzymes despite intact parenchyma.15

EPI can result from various underlying causes15,16:

Image of Pancreatic fibrosis

Pancreatic fibrosis

DECREASED PRODUCTION
of pancreatic enzymes

Loss of functional pancreatic parenchyma or reduced endogenous stimulation of the pancreas can result in decreased production of enzymes

Image of ultrasound of pancreatic cancer

Ultrasound of pancreatic cancer

DECREASED DELIVERY
of pancreatic enzymes to the duodenum

An obstruction in the duct can cause a decrease in the delivery of pancreatic enzymes to the duodenum

Diagram of Gastric bypass surgery

Gastric bypass surgery

DECREASED ACTIVITY
of pancreatic enzymes

Activity of enzymes can be reduced due to intraluminal inactivation or postcibal asynchrony

Conditions and surgical procedures associated with EPI:

Chronic pancreatitis (CP)9,17,18

  • Destruction of functioning pancreatic parenchyma results in insufficient amounts of enzymes being secreted into the duodenum, and EPI
  • ∼6%-22% of patients with CP have EPI at the time of CP diagnosis*
  • The probability of developing EPI increases to 50% 12 years after onset of CP

*Based on a US, retrospective analysis.

†Based on a US, retrospective study evaluating patients with onset of alcoholic or late-onset idiopathic CP.

Cystic fibrosis (CF)9,19

  • Highly concentrated and viscous pancreatic juice blocks the pancreatic ducts leading to acinar atrophy, pancreatic fibrosis, and EPI
  • Approximately 9 out of 10 patients with CF have EPI

‡Based on a US, multi-center study.

Pancreatic cancer1,9,20-25

  • Obstruction of the pancreatic duct by tumors, destruction of the pancreas by tumor growth, and loss of pancreatic tissue from surgery often lead to EPI
  • Prior to surgery: 42%-68% of patients with resectable pancreatic cancer have EPI§
  • Post surgery: 55%-89% of patients with resectable pancreatic cancer have EPI§

§While the majority of these studies included patients who underwent pancreatoduodenectomy for pancreatic adenocarcinoma, some studies include patients who underwent different surgical procedures and/or patients with cancer of the pancreatic region including, but not limited to, periampullary, bile duct, and/or duodenal carcinoma. Additionally, this data includes US and European patient populations.

Pancreatectomy20,26

  • EPI is a common complication of partial or complete removal of the pancreas. EPI has been diagnosed after partial resection of the pancreas including pancreatoduodenectomy (Whipple procedure)

Gastric surgery9

  • Gastric surgical procedures can result in asynchrony between gastric emptying and discharge of bile and pancreatic enzymes resulting in EPI

Obstruction of the biliary or pancreatic duct9,27

  • Blockage of the biliary or pancreatic duct may prevent the release of digestive enzymes into the duodenum leading to EPI

Diabetes mellitus (type I and type IIIC)9,28-34

  • Pancreatic exocrine and endocrine tissue are closely linked both anatomically and physiologically. Conditions that affect one tissue type can cause an impairment in the other
  • Type I diabetes is an autoimmune disease characterized by chronic inflammation of pancreatic islet cells, leading to insulin deficiency, pancreatic fibrosis, and atrophy. The pathophysiological mechanism resulting in EPI is not yet fully understood
  • Type IIIC diabetes, or pancreatogenic diabetes, is a form of secondary diabetes caused by pancreatic conditions, such as chronic pancreatitis

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