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)


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:


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


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


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


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.

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