Anatomy & histology

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Deputy Editor-in-Chief: Raul S. Gonzalez, M.D.
Deepali Jain, M.D.
Jan Hrudka, M.D., Ph.D.

Last author update: 4 August 2021
Last staff update: 4 August 2021

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PubMed Search: Normal pancreas[TI] anatomy histology

Deepali Jain, M.D.
Jan Hrudka, M.D., Ph.D.
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Cite this page: Jain D, Hrudka J. Anatomy & histology. website. Accessed May 19th, 2024.
Definition / general
  • The pancreas is a mixed exocrine and endocrine gland located in the retroperitoneum behind the stomach, in front of the inferior vena cava and the aorta
Essential features
  • Retroperitoneal organ with exocrine and endocrine functions
  • Histology: serous ductal / acinar (exocrine cells) gland with tubuloalveolar arrangement with interspersed islets of Langerhans (endocrine cells)
  • Anatomically, from right to left, the pancreas is divided into the caput (head), collum (neck), corpus (body) and cauda (tail)
  • Pancreatic secretion is drained by the main pancreatic duct (Wirsung duct), with orifice in major duodenal papilla (papilla of Vater), mostly together with the main bile duct
  • ~5 - 10% of people have an accessory pancreatic duct (Santorini duct), with orifice in minor duodenal papilla
  • Pancreas is embedded in fibrous capsule passing in fibrous septa, separating pancreatic lobuli
  • Lobuli consist of multiple acini (the exocrine part) drained by intralobular ducts (leading the pancreatic juice into the small bowel)
  • Interlobular ducts originate from the confluence of many intralobular ducts
  • Interlobular ducts lead to the main pancreatic duct
  • Exocrine function (99% of cells): pancreatic juice is produced by acinar cells
    • Pancreatic juice contains bicarbonate and proteolytic enzymes (trypsinogen, chymotrypsinogen, carboxypeptidase, elastase), lipolytic enzymes (lipase, esterase, phospholipase), saccharide degrading enzyme (amylase), nucleic acid degrading enzymes (DNAse, RNAse)
    • Enzymes are activated in the intestine; enterocyte glycocalyx enzymes (enterokinase) turns trypsinogen to trypsin
    • Trypsin catalyzes activation of the other enzymes
  • Endocrine function (1% of cells): islets of Langerhans consist of several cell types producing various hormones, which are released into the blood
    • A cells (20% of the islets): in the periphery of the islets, glucagon production - increase of blood glucose concentration
    • B cells (70% of the islets): in the center of the islets, insulin production - decrease of blood glucose, glucose intake in adipocytes and muscle cells
    • D cells (5% of the islets): somatostatin production - inhibition of smooth muscle motility, antagonist of several gastrointestinal hormones
    • F cells (1% of the islets): pancreatic polypeptide production - regulation of pancreatic juice and bile release
    • D1 cells (less than 1%): vasoactive intestinal polypeptide - glycogenolysis and hyperglycemia, stimulates GI fluid secretion and causes secretory diarrhea
    • EC (enterochromaffin) cells (less than 1%): P substance, serotonin - stimulation of gastrointestinal motility
    • G cells (less than 1%): gastrin - stimulation of gastric juice release
    • PP cells: pancreatic polypeptide - stimulates secretion of gastric and intestinal enzymes and inhibits intestinal motility
    • Ghrelin producing cells: ghrelin - regulation of hunger and energetic metabolism
  • 15 cm long, 60 - 140 g
  • Shape is akin to letter J turned sideways, with loop of J around the duodenum
  • Divided into head (right of left border of superior mesenteric vein; contains uncinate process), body (between left border of superior mesenteric vein and left border of aorta) and tail
  • Retroperitoneal organ (except for tail), lies within duodenal curve, close to superior mesenteric artery and portal vein
  • Anterior body of pancreas touches posterior wall of stomach
  • Posterior of pancreas touches aorta, splenic vein and left kidney
  • Pancreatic tail extends to the splenic hilum
  • Pancreatic head has close anatomic relationship to the common bile duct (choledochus) - distal part (ca. 4 - 5 cm) passes through the pancreatic head into the small intestine
    • Orifice of the bile duct is called ampulla of Vater (major papilla), which is equipped with circular smooth muscle (sphincter of Oddi) releasing bile and pancreatic juice into the duodenum
    • Pathology of pancreatic head, common bile duct and papilla share clinical symptoms
  • Forms from embryonic foregut, of endodermal origin (Wikipedia: Pancreas [Accessed 7 December 2017])
  • Pancreas forms from ventral and dorsal buds that rotate and fuse
  • Ventral bud (anlage) develops from hepatic duct, forms posterior / inferior head and uncinate process
  • Dorsal bud (anlage) develops from foregut and extends into dorsal mesentery; forms body, tail, anterior head
  • Fusion of ducts at week 7 creates main pancreatic duct (Wirsung), which extends to papilla of Vater, usually with common bile duct
  • Proximal portion of dorsal duct persists as accessory duct of Santorini, empties into minor duodenal papilla
  • Usually numerous anastomotic connections between ducts of Wirsung and Santorini; if not, result is pancreas divisum (10% of individuals), in which duct of Santorini is major drainage duct
  • Percentage of acinar cells decreases after birth
  • Anomalies:
    • In 67% of adults, pancreatic duct empties into common bile duct, not into ampulla directly
    • Abnormal fusion of ventral and dorsal buds causes annular pancreas or heterotopic pancreas
Exocrine pancreas
  • Acini comprise 80% of pancreas
  • Composed of columnar to pyramidal epithelial cells with minimal stroma
  • Basophilic due to prominent rough endoplasmic reticulum
  • Pancreas produces 2 liters/day of bicarbonate rich fluid containing digestive enzymes and proenzymes, regulated by neural stimulation (vagus nerve) and humoral factors (secretin, cholecystokinin)
    • Cholecystokinin: released from duodenum in response to fatty acids, peptides and amino acids; promotes discharge of digestive enzymes by acinar cells
    • Secretin: stimulates water and bicarbonate secretion by duct cells; is stimulated by acid from stomach and luminal fatty acids
  • Pancreatic self digestion is prevented by:
    • Packaging of most proteins as inactive proenzymes, enzyme sequestration in zymogen granules
    • Proenzymes activated only by trypsin, which is activated only by duodenal enterokinase
    • Trypsin inhibitors are present in ductal and acinar secretions
    • Intrapancreatic release of trypsin activates enzymes, which degrade other digestive enzymes before they can destroy pancreas
    • Lysosomal hydrolases can degrade zymogen granules to prevent autodestruction if acinar secretion is impaired
    • Acinar cells themselves are highly resistant to trypsin, chymotrypsin and phospholipase A2
    • Pancreatic ductal epithelia secrete the bulk of secretagogue induced bicarbonate ions by moving HCO3 from the blood into the pancreatic fluid (Said: Physiology of the Gastrointestinal Tract, 6th Edition, 2018)
    • Mucin producing cells are also found among pancreatic ductal epithelia - mucin lubricates, hydrates and protects epithelial cells (Johnson: Encyclopedia of Gastroenterology, 1st Edition, 2004)
Endocrine pancreas
  • Consists of islets of Langerhans; represents 1% of pancreas (percentage higher at birth)
  • Round, compact, highly vascularized with scant connective tissue
  • More irregular outline and trabecular arrangement in posterior head of pancreas, with cells producing pancreatic polypeptide
  • Size of islets usually 0.1 - 0.2 mm; endodermal origin; 1 million islets present in pancreas
  • Postgastrectomy, may get islet hypertrophy, then beta cell proliferation, then atrophy and amylin deposits (Hum Pathol 2000;31:1368)
  • Alpha cells: peripherally dense and round on electron microscopy
  • Beta cells: crystalline appearance on electron microscopy, with surrounding halo
  • Delta cells: large pale granules on electron microscopy
  • PP cells: also scattered in exocrine pancreas; more PP cells in posterior head of pancreas (from ventral bud)
  • Nesidioblastosis:
    • Islets in intimate association with ducts, with formation of ductuloinsular complexes
  • Nesidiodysplasia (Hum Pathol 1988;19:1215):
    • Loss of the usual centrilobular concentration of larger islets, with increased small irregularly distributed aggregates of islet cells
    • Also increase in beta cell nuclear size and DNA content
    • May be associated with endocrine neoplasms
  • Peliosis:
    • Selective congestion and dilation of vessels of islets only, not seen in vessels elsewhere
Drawings / diagrams

AFIP images

Development of human pancreas

Anatomy of pancreas

Anatomy of pancreas

Images hosted on other servers:
Development of pancreas

Development of pancreas



Pancreas of human embryo

Pancreas of human embryo

Stages of development

Stages of development

Microscopic (histologic) description
  • Vast majority of pancreas volume is composed of exocrine tissue (pancreatic acini)
    • Acini show alveolar (round) shape and lobulated architecture
    • Acini are packed closely together, drained by series of ductules and ducts
    • Acinar cells stain blue by hematoxylin at their base because of high RNA content and presence of nuclei
    • Luminal aspect stains pink due to high content of digestive enzymes (zymogen granula, staining with PAS)
    • Ductules and ducts are lined by a single layer of cuboidal or cylindrical epithelia
    • There is a significant amount of collagen within the wall of large ducts, including main pancreatic duct
  • Embedded within the pancreatic exocrine tissue are the islets of Langerhans
    • Islets display rich vascularization and consist of endocrine cells
    • Endocrine cells have polygonal to round shape, voluminous pale to slightly eosinophilic cytoplasm and monomorphic round nuclei with heterogenous (salt and pepper) chromatin
Microscopic (histologic) images

Contributed by Jan Hrudka, M.D., Ph.D.
Normal pancreas histology Normal pancreas histology

Normal pancreas histology

Normal pancreas histology Normal pancreas histology

Normal pancreas histology

Chromogranin A IHC Chromogranin A IHC detail

Chromogranin A IHC

Glucagon IHC Glucagon IHC detail

Glucagon IHC

Insulin IHC Insulin IHC detail

Insulin IHC

Contributed by Grigory Demyashkin, M.D., Ph.D. and AFIP images

10 week old fetus

Islets in newborn

Adult pancreas: distribution of islet cell types

6 - 8 week embryo

Cytology description
  • Smear, cytospins or cytoblock from brushings or needle aspirates from ducts; eventually fine needle aspirations (FNAs) from solid tissue
  • FNA - predominant cell type is acinic: pyramidal or triangular cells with abundant granular cytoplasm and round eccentric or central nucleus with fine chromatin and often distinct nucleolus
  • Ductal cells = 2 dimensional flat sheets (honeycomb), picket fence appearance, tall or cuboidal cells with scant pale cytoplasm and basally located bland appearing nuclei
  • Contaminants = mesothelia or hepatocytes in transcutaneous biopsies, duodenal or gastric mucosa in endoscopic aspirations (more often)
Cytology images

AFIP images

Normal pancreatic acinar cells

Normal ductal cells in sheet arrangement

Positive stains
Electron microscopy images

AFIP images

38 / 39 week old fetus

Adult pancreatic islet cells

2 centroacinar cells with electron lucent cytoplasm

Images hosted on other servers:

Zymogen granules

Board review style question #1
Elastase, trypsin and DNAse are placed in the

  1. Basophilic basal part of acinic cells
  2. Cytoplasmic vacuoles in the ductal cells
  3. Eosinophilic cytoplasm of beta cells
  4. Eosinophilic granula in the acinic cells
Board review style answer #1
D. Eosinophilic granula in the acinic cells. As basic substances, proteins are usually eosinophilic in H&E staining. The eosinophilic granula are called zymogenic in pancreas acinic cells. Answer A is incorrect because the basophilic part of the acinic cell cytoplasm contains ribosomes (rough endoplasmic reticulum). Answer B is incorrect because vacuoles in the ductal cells contain mucin. Answer C is incorrect because beta cells are a major part of Langerhans islets; eosinophilic cytoplasm contains endocrine granula (insulin).

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Reference: Pancreas - Anatomy & histology
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