The pancreas is a glandular organ located in the retroperitoneum between the duodenal curvature and the splenic hilum. It has both exocrine and endocrine functions and is anatomically classified into four parts: the head, neck, body, and tail. Because it is embryologically derived from the foregut, the pancreas receives arterial supply from the celiac trunk and its branches. The veins of the pancreas drain into the portal vein and the lymphatics eventually drain into the celiac, superior mesenteric, and splenic lymph nodes. The pancreas receives both sympathetic and parasympathetic innervation via the celiac ganglia. Histologically, the pancreas has two functional structures: the exocrine acinar glands and the endocrine pancreatic islets. The exocrine glands produce digestive enzymes, which are secreted into the duodenum, and the endocrine islets produce blood glucose-regulating hormones such as insulin and glucagon, which are secreted into the blood.
- Glandular organ
- Length: 12–15 cm
- Weight: approx. 80 g
Anatomical subdivisions of the pancreas 
- Neck: lies anterior to the portal vein
- Body: lies anterior to the aorta and extends to the left kidney
Pancreatic ducts 
- Pancreatic duct (duct of Wirsung): extends from the tail to the head of the pancreas
- Accessory pancreatic duct (duct of Santorini): begins in the head and drains the pancreatic head and body → empties at the minor duodenal papilla
Vasculature, lymphatics, and innervation of the pancreas 
- Lymphatics: celiac, superior mesenteric, and splenic lymph nodes → paraaortic lymph nodes
- Innervation: celiac ganglia
- > 90% of the pancreas
- Produces digestive enzymes that are secreted into the gastrointestinal tract (see ”” below)
- Composed of serous glandular tissue that is separated into lobules by collagenous septae
- Units of secretory acinar cells surrounding a small lumen
- Secrete proenzymes (e.g., trypsinogen, chymotrypsinogen) into intercalated ducts → ducts eventually merge to form the pancreatic duct → duct carries the enzymes out of the pancreas and to the duodenum
- Centroacinar cells: pale cells in the center of the acini, which secrete bicarbonate ions into the pancreatic fluid
- Electron micrographs of acinar cells show:
Histologically, the exocrine pancreas closely resembles the salivary glands. However, unlike the salivary glands, the pancreatic exocrine glands lack myoepithelial cells in the acini and do not possess striated ducts. Additionally, centroacinar cells are unique to the pancreas.
- Produces different hormones that are primarily involved in the regulation of blood glucose levels (see “” below)
- Composed of islets of Langerhans embedded within the exocrine pancreas
Pancreatic ducts 
- Smaller ducts have cuboidal epithelium.
- Larger interlobular ducts have columnar epithelium.
- Most pancreatic malignancies are adenocarcinomas that originate in the ductal epithelium. 
The pancreatic fluid is isotonic. It contains the following:
Digestive pancreatic enzymes
Pancreatic proteases: digestion of proteins
- Secreted as inactive proenzymes (zymogens) by pancreatic acinar cells into the pancreatic duct
Trypsin and chymotrypsin
- Proenzymes: trypsinogen and chymotrypsinogen
- Activated in the duodenum: Trypsinogen is activated to trypsin by enterokinases, which are located at the brush border of the duodenal and jejunal mucosa.
- Once activated, trypsin activates chymotrypsinogen to form chymotrypsin and, furthermore, converts additional trypsinogen molecules to trypsin (positive feedback loop).
- Elastase (activated by trypsin)
- Carboxypeptidase: activated by trypsin
- Pancreatic amylase (secreted in active form): digestion of carbohydrates
- Pancreatic lipase: digestion of lipids
- Phospholipase A: digestion of phospholipids
- Nucleases: digestion of RNA/DNA
- Pancreatic proteases: digestion of proteins
- Electrolytes (Na+, K+, Cl-, HCO3-): Concentration of Cl- and HCO3- increases with the rate of pancreatic juice secretion
Cystic fibrosis is caused by a defective chloride channel that impairs pancreatic water and electrolyte secretion. This results in obstruction of the pancreatic ducts, with subsequent maldigestion and malabsorption.
- Inhibition: somatostatin
Main endocrine cell types and hormones produced
|Overview of islets of Langerhans cell types|
|Cell types||Substance secreted||Function||Stimulation||Inhibition|
|α-cells|| || |
|δ-cells|| || |
|ε-cells|| || || |
|PP cells (formerly γ-cells)|| || || |
Insulin synthesis and regulation
Insulin synthesis 
- Insulin gene transcription and translation in the rER of pancreatic β-cells → preproinsulin (precursor protein)
- Signal proteases remove the signal peptide of preproinsulin → proinsulin
- Protein folding and formation of one disulfide bridge in the α-chain and two disulfide bridges between the α-chain and β-chain
- Proinsulin is transported to the Golgi apparatus → packaged in membrane-bound secretory granules with proprotein convertases
- Proinsulin is cleaved by proteases → mature insulin and C-peptide
- Secretion of insulin and C-peptide via exocytosis
Regulation: The secretion of insulin is chiefly regulated by the levels of serum blood glucose. 
- lInsulin secretory pathway: GLUT2-mediated transfer of glucose into the pancreatic β cells → ↑ glucose metabolism → ↑ ATP production → closure of ATP-sensitive potassium channels → cell membrane depolarization → opening of voltage-gated calcium channels → ↑ intracellular calcium levels → ↑ insulin secretion
- Insulin release stimulants 
Insulin release inhibitors 
- α2 agonists
C-peptide is released by the β-cells in an equimolar proportion to insulin but is not present in exogenous insulin. It can, therefore, be used to differentiate between endogenous (e.g., insulinoma, sulfonylurea use) and exogenous hyperinsulinism.
Oral glucose results in a greater increase in insulin levels than IV administration.
- Origin: derived from the foregut (endoderm)
- The endoderm forms ventral and dorsal pancreatic buds.
- Foregut rotation: ventral pancreatic bud fuses with the dorsal pancreatic bud
- Secondary retroperitonealization
- The pancreas comes to rest under the lesser sac (omental bursa).
Impaired development 
Annular pancreas: failure of the ventral pancreatic bud rotation → fusion of the ventral and dorsal buds → formation of a pancreatic ring around the second part of the duodenum → duodenal compression (preampullary or postampullary)
- Associated with Down syndrome
- Clinical features
- Imaging findings: x-ray (if duodenal stenosis is present) on
- Pancreas divisum: failure of the ventral and dorsal buds to fuse by the 8th week of gestation results in separate drainage of the dorsal and ventral pancreatic ducts via minor and major duodenal papillae respectively
- Annular pancreas: failure of the ventral pancreatic bud rotation → fusion of the ventral and dorsal buds → formation of a pancreatic ring around the second part of the duodenum → duodenal compression (preampullary or postampullary)
- See also “ .”