Exocrine Pancreas

Anatomy and Function

The pancreas is a mixed gland with both exocrine and endocrine components. The exocrine portion comprises approximately 85% of pancreatic mass and is organised into lobules of secretory acinar cells and a branching duct system. Scattered between the acini are islets of Langerhans, which form the endocrine pancreas.

The exocrine pancreas supports digestion through secretion of digestive enzymes and an alkaline, bicarbonate-rich fluid. Together they facilitate the breakdown of carbohydrates, proteins and lipids and neutralise gastric acid.

The Functional Unit

The functional unit of the exocrine pancreas consists of an acinus and its associated duct system. The word acinus is from the Latin term for “berry in a cluster”.

• Acinar cells: specialise in the synthesis, storage and secretion of digestive enzymes.
• Ductal cells: secrete bicarbonate and water, modifying the aqueous component of pancreatic juice.

Secretions drain from small ductules into the main pancreatic duct, which joins the common bile duct to form the ampulla of Vater before opening into the second part of the duodenum.

Pancreatic exocrine secretion is stimulated primarily by parasympathetic activity and gastrointestinal hormones in response to food intake.

By OpenStax College [CC BY 3.0], via Wikimedia Commons

Fig 1
The functional unit of the exocrine pancreas includes the acinus and its duct system.

Pancreatic Secretions

Pancreatic acinar cells synthesise and secrete enzymes.

Other secreted enzymes include elastase, ribonuclease and gelatinase.

The pancreatic duct system secretes a bicarbonate-rich fluid, which has two key roles:

• Neutralise acidic chyme – entering the duodenum from the stomach.
• Optimise pH – pancreatic enzymes function best in a neutral to alkaline environment.

Secretion of Digestive Enzymes

Digestive enzymes are synthesised on the rough endoplasmic reticulum, processed in the Golgi apparatus, and packaged into secretory granules. Many protein-digesting enzymes are stored and secreted as inactive zymogens, which helps to prevent auto-digestion of the pancreas.

Once secreted into the duodenum, the brush-border enzyme enteropeptidase cleaves trypsinogen into trypsin, triggering a cascade of pancreatic zymogen activation, amplifying digestion.

Secretion of Bicarbonate and Water

Bicarbonate is produced within ductal cells via carbonic anhydrase, which catalyses the reaction between water (H₂O) and carbon dioxide (CO₂). This produces carbonic acid (H₂CO₃).

Within ductal cells, carbonic anhydrase catalyses a reaction between water (H₂O) and carbon dioxide (CO₂) to produce carbonic acid (H₂CO₃).

H₂O + CO₂ -> H₂CO₃

Carbonic acid then dissociates into hydrogen ions (H⁺) and bicarbonate ions (HCO₃^–).

H₂CO₃ -> H⁺ + HCO₃^–

The bicarbonate ions (HCO₃^–) are transported into the intercalated ducts of the pancreas in exchange for luminal chloride ions (Cl^–). This chloride is recycled back into the lumen via CFTR, a cAMP activated luminal chloride channel. Some bicarbonate ions also enter the cell directly through this CFTR channel.

Meanwhile, the hydrogen ions are removed by exchanging for sodium ions (Na⁺) in the blood via a H⁺/Na⁺ antiporter. Some of these Na⁺ are transported across the ductal cell into the ductal lumen via another Na⁺/H⁺ antiporter.

An intra-luminal negative charge also pulls Na⁺ ions into the lumen through the tight junctions between cells. Overall, the movement of sodium and bicarbonate ions into the lumen creates an osmotic gradient pulling water into the ducts.

The HCO₃^– ions, Na⁺ ions and water then move through the intercalated ducts to the main pancreatic duct ready for secretion into the duodenum upon an appropriate stimulus.

Created in BioRender

Fig 2
Bicarbonate secretion in the pancreatic duct.

Regulation of Pancreatic Secretion

Pancreatic secretion is regulated through both neural and hormonal mechanisms.

Neural Regulation

Parasympathetic vagal stimulation promotes enzyme secretion on seeing, smelling or tasting food, and in response to gastric distension.

Hormonal Regulation

Two major hormones released from the small intestine stimulate pancreatic secretion.

Secretin from the S cells in the duodenum:

• Is released in response to acidic chyme.
• Stimulates bicarbonate secretion into pancreatic fluid – by increasing availability of cAMP and chloride recycling by CFTR in ductal cells.

Cholecystokinin (CKK) from the I cells in the duodenum:

• Is released in response to fatty acids and amino acids in the chyme.
• Stimulates secretion of enzyme-rich pancreatic fluid.
• Promotes bile secretion via gallbladder contraction – cholecystokinin literally means “bile sac move”.

Clinical Relevance

Tumours of the Pancreas

The most common pancreatic malignancy arises from the exocrine pancreas and is termed pancreatic ductal adenocarcinoma (PDAC).

Tumours may obstruct the pancreatic duct, impairing the delivery of pancreatic enzymes and bicarbonate into the duodenum. This can result in pancreatic exocrine insufficiency, leading to malabsorption, diarrhoea and weight loss.

PDAC is frequently diagnosed at an advanced stage, as early disease is often asymptomatic. Surgical resection is the only potentially curative treatment, but many patients are not suitable candidates at diagnosis, contributing to a poor overall prognosis.

By user:KGH (Own work) [GFDL (http://www.gnu.org/copyleft/fdl.html) or CC-BY-SA-3.0 (http://creativecommons.org/licenses/by-sa/3.0/)], via Wikimedia Commons

Fig 3
H&E stain of pancreatic adenocarcinoma.