Pancreas histology

Secretory units

The exocrine component of the pancreas makes up about 98% of the pancreatic tissue. It is comprised of densely packed serous acinar (tubuloacinar) glands. These glands are called pancreatic acini, which represent the secretory units of the pancreas. They are formed out of simple epithelium. Each pancreatic acinus consists of pyramidal-shaped acinar cells, which have a broad basal portion and a narrow apical surface that surround a small central lumen.

These acinar cells are serous secretory cells that produce digestive enzymes. Their secretory function is attested by the presence of abundant rough endoplasmic reticulum and Golgi apparatus. Seen under a microscope, their basal cytoplasm is largely basophilic, with distinct acidophilic zymogen granules in their apical poles.

Zymogen granules are large secretory organelles in which acinar cells store their inactive enzymes, called zymogens or proenzymes. Upon stimulation, the zymogens are activated and the acinar cells release their secretions by way of exocytosis. During exocytosis, the granules merge with the cell membrane and expel their contents into the lumen of the acinus. 

Duct system

Once synthesized, the pancreatic secretions leave the acini via the intercalated ducts. The latter are short ducts with a small lumen that start within the acini. The initial, intra-acinar portion of the intercalated duct is lined by simple squamous epithelial cells called centroacinar cells, which signify the beginning of the ductal system of the exocrine pancreas. These pancreatic cells contain a centrally placed, flat nucleus and appear lightly stained with hematoxylin and eosin (H&E).

Centroacinar cells are continued by simple, low cuboidal ductal cells that line the extra-acinar portion of the intercalated ducts which extends outside the acinus. Intercalated ducts drain into intralobular ducts, which are lined by simple, low columnar epithelium.

In turn, the intralobular ducts flow into the larger caliber interlobular ducts, which are located within the interlobular connective tissue septa. These are also lined by low columnar epithelium that becomes taller and more stratified as the size of the ducts increases. The interlobular ducts drain into the main pancreatic duct (of Wirsung), or sometimes into the accessory pancreatic duct (of Santorini). These ducts are lined by the high columnar epithelial cells that are most often stratified. 

The main pancreatic duct travels from the tail to the head of the pancreas, collecting secretions from all the interlobular ducts along the way. It merges with the gallbladder’s (common) bile duct to form the hepatopancreatic ampulla (of Vater), which empties into the descending part of the duodenum at the major duodenal papilla. This papilla is surrounded by a thickened smooth muscle layer called the sphincter of ampulla (hepatopancreatic sphincter of Oddi). This controls the flow of both the pancreatic secretions and bile into the duodenum. The accessory pancreatic duct (of Santorini), when present, drains the head of the pancreas and empties into the duodenum through the minor duodenal papilla. 

Function

Pancreatic cells secrete about 1.5 L of fluid each day. The presence of acidic chyme, fats and proteins in the duodenum stimulates enteroendocrine (APUD) cells of the small intestine to release secretin and cholecystokinin (CCK) into the bloodstream. These intestinal hormones are the primary regulators of pancreatic secretions. In addition to this hormonal mechanism, the activity of the exocrine pancreas is also regulated by parasympathetic innervation via the vagus nerve.

Secretin and CCK work in unison to induce the secretion of pancreatic juice or fluid. The majority of pancreatic fluid is comprised of water with large amounts of sodium and bicarbonate ions. This highly alkaline fluid is secreted by the centroacinar and intercalated ductal cells in response to secretin. This response serves to neutralize the acidity of the duodenum and form an optimal environment for the activity of pancreatic enzymes.

Pancreatic enzymes represent the active ingredient of the pancreatic fluid. They are produced, stored and secreted by acinar cells in response to CCK. Pancreatic enzymes are extremely potent and can digest any type of macromolecule, hence they are secreted in the aforementioned inactive forms (proenzymes). These enzymes are divided based on the specific substance they normally digest:

Pancreatic enzymes only get activated inside the duodenum under the influence of a proteolytic enzyme called enterokinase, which is secreted by the duodenal mucosa. Enterokinase first transforms trypsinogen into the extremely potent trypsin. Once active, trypsin catalyzes a cascade of activation of all the other pancreatic enzymes. The requirement of an alkaline environment and the segregation of enterokinase in the duodenum prevents the undesired activation of these enzymes within the pancreas. 

Expand your knowledge about the pancreas with the following resources:

Histology

The endocrine component makes up about 2% of the pancreas, which is represented by about 1-2 million pancreatic islets (of Langerhans). They are dispersed throughout the exocrine component of the pancreas, most of them being located in the tail region. These islets are demarcated from the rest of the parenchyma by a delicate sheath of reticular fibers.

The pancreatic parenchyma, especially its ducts, consist of several types of epithelial tissue. Ease your learning and start recgonizing the main types of epithelial tissue using Kenhub's labelling exercises and quizzes! 

Pancreatic Islets are spherical clusters of polygonal endocrine cells. On a pancreas histological slide stained with H&E, they appear as large, pale-staining cells enveloped by intensely staining, basophilic pancreatic acini. The cells of the islets are connected to each other with desmosomes and gap junctions, forming bands or cords of cells. Pancreatic islets are permeated by many fenestrated capillaries, which allow quick entry of pancreatic hormones into the blood. 

There are four main types of cells in the pancreatic islets:

• B (beta) cells - these cells secrete insulin and constitute about 70% of the islet cells. They are most commonly located in the central part of the islet. B cells contain many secretory granules which possess a dark center with crystallized insulin, surrounded by a wide pale halo.
• A (alpha) cells - these cells secrete glucagon and constitute 15-20% of the islet cells. They are usually larger than B cells and most commonly located peripherally in the islet. Their granules are more uniform in size, with a larger dark center surrounded by a thinner halo compared to B cells. The granules are filled with glucagon.
• D (delta) cells - these cells secrete somatostatin and constitute 5-10% of the islet cells. They are located diffusely throughout the islet but most commonly in the periphery. D cells contain larger secretory granules compared to A and B cells. 
• PP (pancreatic polypeptide) cells - these cells secrete pancreatic polypeptide and constitute <5% of the islet cells. They are mostly located within the head of the pancreas. 

On histology slides, the pancreas can look very similar to other glandular tissue, such as the parotid gland. However, one unique feature of the pancreas that differentiates it from other glands are the pancreatic islets, which are clearly demarcated from the pancreatic acini. A second feature is the intercalated ducts of the pancreas, which start from within the acinus rather than being a continuation of the acinus, like seen in other glands.

Function

The hormones of the endocrine pancreas are the primary regulators of glucose, lipid and protein metabolism.

Insulin 

Insulin exhibits its effects on most cells of the body, most notably those of the liver, muscles, and adipose tissue. The main function of insulin is related to glucose metabolism, decreasing blood glucose, and sparing proteins and lipids by way of several mechanisms:

• Stimulates uptake of glucose in insulin-dependent tissues via GLUT4 channels
• Stimulates utilization of glucose by activating intracellular glycolysis
• Stimulates storage of glucose in the form of glycogen and inhibits glycogenolysis
• Stimulates the release of glycerol and fatty acids from VLDL by stimulating the expression of lipoprotein lipase (LPL) in adipose tissue. This enables the entry of fatty acids and monoglycerides into the adipose tissue, where they are converted back to triglycerides and stored.
• Inhibits the activity of LPL in the muscle tissue, preventing the fatty acids and glycerol utilization within it during the time they are being stored in the adipose tissue.
• Stimulates protein synthesis in skeletal muscle cells and hepatocytes
• Inhibits lipid oxidation and protein catabolism

Glucagon 

Glucagon is the antagonistic hormone of insulin. Overall, glucagon causes an increase in blood glucose, increased proteolysis and lipolysis by way of several mechanisms: 

• Stimulates glucose synthesis by promoting gluconeogenesis
• Stimulates the release of stored glucose by promoting glycogenolysis
• Stimulates mobilization of fats from adipose tissue
• Stimulates lipid oxidation by activating hepatic lipase
• Stimulates proteolysis
• Stimulates the activity of LPL in the muscle tissue during fasting.

Somatostatin 

This hormone inhibits the release of insulin and glucagon through local paracrine action. Somatostatin is identical to a hormone secreted by the hypothalamus, which inhibits the release of growth hormone (GH) and thyroid stimulating hormone (TSH) from the anterior pituitary.

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