Pancreatic Secretion

  • The exocrine pancreas secretes an aqueous mixture into the duodenum composed of digestive enzymes, which aid in further degradation of ingested food, and bicarbonate which helps neutralize stomach acid. Neutralization of gastric acid is a critical function of the pancreas as the small intestine mucosa is specialized for nutrient absorption and thus cannot possess a thick protective mucous layer similar to that of the stomach. Furthermore, pancreatic digestive enzymes are optimally active at basic pHs and thus pancreatic bicarbonate secretion is a key requirement for proper digestion.
Bicarbonate Secretion
  • Overview
    • Pancreatic bicarbonate secretion is essentially the reverse of stomach acid secretion and primarily occurs in pancreatic ductal cells. Here, Carbon Dioxide is combined with water to form carbonic acid; subsequently, the bicarbonate ion is transported into the pancreatic duct while the hydrogen ion is transported into the blood stream.
  • Molecular Mechanism
    • CO2 within pancreatic ductal cells is transformed, by carbonic anhydrase, to H2CO3, which immediately splits into H+ and HCO3-. The generated H+ ion is secondarily actively transported into the blood stream using an Na+-H+ antiporter on the cell's basolateral membrane. The generated HCO3- ion is also secondarily actively transported transported into the ductal lumen together with a sodium ion. Additionally, the transport of bicarbonate and sodium ions into the ductal lumen results in passive osmosis of water into the duct which helps actuate flow of pancreatic fluid into the small intestine.
Digestive Enzyme Secretion
  • Overview
    • Pancreatic enzymes are synthesized and stored in pancreatic acinar cells as inactive zymogens. As a result, these powerful digestive enzymes are prevented from destroying pancreatic tissue. As described below, these enzymes only become active once fully secreted into the body of the small intestine which possess sufficient mucosal protection.
  • Pancreatic Enzymes
    • The exocrine pancreas secretes a variety of digestive enzymes specialized for degradation of all the different basic biological macromolecules (The names mentioned below are for the active forms of these enzymes). Carbohydrates are digested by pancreatic amylase.
    • Proteins are digested by trypsin, chymotrypsin, elastase, and carboxypeptidase. Fats are digested by lipase, phospholipase, Cholesterol Esterase. Nucleic Acids are digested by a variety of nucleases.
  • Activation
    • Pancreatic zymogens are activated in a cascade like architecture once fully secreted into the duonenal lumen. The activation cascade is initiated by Enterokinase, an enzyme solely secreted by the cells of the duodenal small intestine mucosa which face the intestinal lumen. Because of this pancreatic zymogens remain fully inactive until they exit the main pancreatic duct, thus protecting pancreatic tissue from their digestive action. Enterokinase processes inactive trypsinogen to trypsin; subsequently, trypsin goes on to process the rest of the zymogens into their active forms. Because enterokinase is only secreted by the duodenal small intestine mucosa zymogen activation only occurs in the intestinal lumen.
  • Pancreatic secretions are primarily regulated by three factors which act synergystically to potentiate one another's effects.
  • Acetylcholine: Released by vagal efferents primarily stimulates synthesis of digestive enzymes by pancreatic acinar cells
  • Cholecystokinin: is released by I Cells in the duodenum and jejunum upon entry of food and primarily stimulates synthesis of digestive enzymes by pancreatic acinar cells
  • Secretin: is released by S Cells of duodenum in response to entry of low pH stomach acid and primarily stimulates production of aqueous sodium bicarbonate solution by pancreatic ductal cells
Phases of Pancreatic Secretion
  • Overview
    • Secretion of pancreatic fluid can be divided into three phases which correspond to the different stages of food ingestion. Each phase tends to induce a slightly different composition of pancreatic secretion with slightly different regulatory mechanisms.
  • Cephalic Phase
    • This phase is initiated by the sensory experience of seeing and eating food and primarily involves vagus nerve stimulation of acinar cells to produce digestive enzymes. Because little aqueous sodium bicarbonate solution by ductal cells these enzymes lie inactive within the pancreatic acini and ducts.
  • Gastric Phase
    • This phase is initiated by the presence of food within the stomach and is once again primarily involves vagus nerve stimulation of acinar cells to produce digestive enzymes. By the end of the cephalic and gastric phases, the pancreatic ducts are filled with inactive digestive zymogens ready for washing out into the intestinal lumen by aquous sodium bicarbonate solution.
  • Intestinal Phase
    • This phase is initiated by emptying of stomach contents into the small Intestine and involves release of both secretin and cholecystokinin which stimulate pancreatic ductal cells to synthesize aqueous sodium bicarbonate solution. The generation of aqueous sodium bicarbonate solution washes out all of the inactive pancreatic enzymes waiting within the pancreatic ducts into the duodenum where they activated as discussed previously.