The pancreas: PEI & PERT

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The human pancreas gland is pinkish tan in colour, 14-18cm long in adults, and weighs approximately 100g in adult males, 85g in adult females, and 5g in newborns. The organ is divided into 4 regions: the head (with the greatest mass), the neck, the body, and the tail, where the main drainage channel for pancreatic exocrine secretion begins through convergence of smaller ducts.

The pancreas produces and secretes more protein per gram of tissue than any other organ, secreting between 6g and 20g of digestive enzymes per day in an average fluid volume of 2.5 litres.

Optimal digestion and absorption of nutrients requires pancreatic enzymes, in particular the enzyme classes of lipase, amylase, and protease.


The pancreas plays a dual role in your bodily functions:

  • Endocrine system: The pancreas secretes hormones, including the blood sugar regulating hormones insulin and glucagon.
  • Exocrine system: The pancreas also secretes enzymes into your digestive tract through a duct into your duodenum.

Endocrine system

As part of the endocrine system, the pancreas secretes two main hormones that are vital to regulating your glucose (also known as blood sugar) level:

  • Insulin: The pancreas secretes this hormone to lower blood glucose when levels get too high.
  • Glucagon: The pancreas secretes this hormone to increase blood glucose when levels get too low.

Balanced blood glucose levels play a significant role in your liver, kidneys, and even your brain. Proper secretion of these hormones is important to many bodily systems, such as your nervous system and cardiovascular system.

Exocrine system

As part of your exocrine system, the pancreas secretes enzymes that work in tandem with bile from the liver and gallbladder to help break down substances for proper digestion and absorption.

Enzymes produced by the pancreas for digestion include:

  • lipase to digest fats
  • amylase to digest carbohydrates
  • chymotrypsin and trypsin for digesting proteins

The pancreas is part of a larger digestive process that begins in the stomach:

  1. The pancreas produces enzymes as soon as food reaches the stomach.
  2. These enzymes travel through a series of ducts until they reach the main pancreatic duct.
  3. The main pancreatic duct meets the common bile duct, which carries bile from the gallbladder and liver towards the duodenum. This meeting point is called the ampulla of Vater.
  4. Bile from the gallbladder and enzymes from the pancreas are released into the duodenum to help digest fats, carbohydrates, and proteins so they can be absorbed by the digestive system.


Pancreatic exocrine insufficiency (PEI) occurs when amounts of enzymes secreted into the duodenum in response to a meal are insufficient to maintain normal digestive processes.

The main clinical consequence of PEI is fat maldigestion and malabsorption, resulting in steatorrhoea.

A serious and life-threatening condition, PEI is caused by underlying diseases affecting pancreatic function, such as cystic fibrosis, chronic pancreatitis, and procedures such as pancreatic surgery.

The pathological mechanism of PEI may vary according to the aetiology of the underlying disease, but in all cases results in insufficient bicarbonate and digestive enzyme secretion by the pancreas and consequently maldigestion.

The symptoms associated with maldigestion due to PEI include lack of appetite, steatorrhea, abdominal cramps, epigastric pain, and flatulence. Left untreated, PEI leads to malnutrition which can thereby contribute to an increase in the morbidity and mortality associated with the underlying disease.

Lipid maldigestion is the main cause of faecal energy loss, leading to the major acute symptoms of PEI, although amylase and protease are also needed for adequate digestion of carbohydrates and proteins.


In clinical practice, the diagnosis of PEI begins with an assessment of the patient’s clinical state, a self-report of bowel movements and weight loss in adults or failure to thrive in children, followed by morphological and functional assessments. Pancreatic enzyme replacement therapy (PERT) can be trialled, and symptom improvement would support a diagnosis of PEI.


The primary treatment goal for PEI is to eliminate maldigestion/malabsorption and maintain adequate nutrition. Ideally, treatment would perfectly mimic the exocrine secretory response of a healthy pancreas in terms of the quantity, composition and timing of luminal enzymatic activity.

Pancreatic enzyme replacement therapy (PERT) is the mainstay of treatment for PEI. In patients suffering from PEI, PERT facilitates the digestion and subsequently the absorption of fats, proteins, and carbohydrates.

The objective of PERT is to deliver sufficient enzymatic activity into the duodenal lumen simultaneously with the meal in order to restore nutrient digestion and aid absorption. Struyvenberg et al. recommend PERT should be taken with the first bite of a meal and consider adding extra enzymes during or towards the end of the meal. “Thus, if consumption of a meal is less than 15 min, all enzymes can be taken at the beginning of the meal; for a 15- to 30-minute meal, we suggest taking half the enzyme capsules with the first bite and the other half in the middle of the meal; for more than 30 minutes, we recommend taking one third at the beginning, one third in the middle and one third at the end. The rationale for taking pancreatic enzymes throughout the meal is to mimic the action of our own endogenous pancreatic enzymes, where secretion from the gland occurs throughout a meal.”

The dosage of pancreatic enzyme replacement therapy is based on lipase units/kg/meal, lipase units/g fat intake, or lipase units/meal depending on the underlying disease and is dictated by the degree of PEI and the amount of fat in the diet.

Modern preparations contain pancreatic extract encapsulated in microtablets or mini-microspheres with pH-sensitive enteric coating. The enzymes mix intragastrically with the chyme while being protected from acid degradation by the enteric coating. The enzymes are then emptied from the stomach simultaneously with the chyme. The higher pH in the duodenum dissolves the enteric coating, releasing the enzymes at the appropriate site for digestion and absorption.


PERT may be an unfamiliar type of treatment for patients; thus, there is an opportunity for pharmacists to play an active role in PEI management. Before dispensing PERT, it is imperative that patients understand both the dosing schedule and what to expect with treatment. Pharmacists should also instruct patients to speak with their physician before discontinuing therapy. Pharmacist specific goals for patients with PEI should include dose verification, proper expectation setting, appropriate treatment administration, and comprehensive PERT counselling.


1. Explain how pancreatic exocrine insufficiency (PEI) affects digestion.

2. Talk about how PERT supplies enzymes to the body to help break down food.

3. Explain the importance of being compliant and taking PERT as directed by the physician.

4. Direct patients to take PERT every time they eat meals and snacks.

5. If appropriate, include the caregiver in consultations about how to help patients take PERT.

6.  Emphasise the importance of taking PERT with food to help maximize nutrient absorption.

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