Physiology and function of the pancreas

Chapter 1.6
Physiology and function of the pancreas

Yiannis N. Kallis¹ and David Westaby²

¹Barts Health NHS Trust, London, UK

²Imperial College Healthcare NHS Trust, London, UK

1.6.1 Anatomy, physiology and function

The pancreas is a retroperitoneal organ located in the upper abdomen. It extends transversely between the concavity of the duodenum and the spleen, and lies posteroinferior to the stomach. The medial aspect of the pancreas receives a blood supply from branches of the gastroduodenal and superior mesenteric arteries, whilst branches of the splenic artery supply the bulk of the pancreatic body and tail. Blood drains into the portal venous system via the superior mesenteric and splenic veins. Lymph drainage of the pancreas is via splenic, coeliac and superior mesenteric lymph nodes, which are common sites of metastatic cancer spread.

The pancreas performs both exocrine and endocrine functions and plays a central role in digestion and glucose metabolism. Pancreatic exocrine secretions drain into the medial aspect of the second part of the duodenum via tributaries that form the main pancreatic duct. The duct enters the duodenum at the ampulla of Vater, into which the common bile duct also drains. Outflow is controlled by a smooth muscle sphincter termed the sphincter of Oddi. Endocrine cells of the pancreas release hormones directly into the bloodstream.

The exocrine pancreas consists of units called acini, which are arranged into lobules and drain into the main pancreatic duct. They make up 98% of the pancreatic mass and are responsible for the production of digestive enzymes and pancreatic fluid. Enzymes, such as trypsin, chymotrypsin, lipase, phospholipase A2 and amylase, are stored as inactive precursors within secretory granules and are released under neurohormonal control. These proenzymes are activated by intestinal enteropeptidases only upon reaching the duodenum, thereby preventing pancreatic autodigestion due to premature activation. Dysregulation of these mechanisms is thought to underpin the pathogenesis of pancreatitis. Enzymes are released in large quantities for the early digestion of proteins, fats and carbohydrates. Pancreatic ductal cells secrete approximately 2 L of bicarbonate-rich fluid daily to neutralise duodenal chyme and optimise conditions for digestion.

Exocrine function is governed by multiple neurohormonal pathways triggered by the process of eating. The autonomic nervous system directly induces pancreatic enzyme release via vagal parasympathetic efferents in response to cephalic stimuli (e.g. the sight and smell of food), and also after gastric distension. Duodenal exposure to food and acidity induces the release of gut hormones from specialised intestinal enteroendocrine cells. Cholecystokinin governs acinar cell degranulation and secretin is primarily responsible for alkaline pancreatic secretion.

Endocrine cells are distributed throughout the pancreas in spherical clusters called islets of Langerhans, which are criss-crossed by a dense network of capillaries. Beta-cells, the predominant cell type, are responsible for insulin production and alpha-cells synthesise glucagon, both key hormones in glucose homeostasis. Other cell types secrete inhibitors of pancreatic exocrine secretion, such as somatostatin, which also have inhibitory effects on islet cell function.