Pancreatic secretion

Definitions & Key takeaways

Pancreatic secretion refers to the production and release of enzymes and hormones by the pancreas, a gland located behind the stomach. These enzymes and hormones aid in the digestion of food and the regulation of blood sugar levels. The pancreas produces both exocrine and endocrine secretions. Exocrine secretions include enzymes such as amylase, lipase, and trypsin, which are released into the small intestine to aid in the digestion of carbohydrates, fats, and proteins. Endocrine secretions include insulin and glucagon, which regulate blood sugar levels.

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Introduction0:00–0:41

The pancreas is a long, skinny gland the length of a dollar bill and is located in the upper abdomen, or the epigastric region, behind the stomach.
It has endocrine functions meaning it secretes hormones into the blood that eventually act upon other target tissues. For example, alpha and beta cells in the pancreas make hormones like insulin and glucagon that are secreted into the bloodstream to regulate blood sugar levels.
However, approximately 90% of the pancreas is dedicated to its exocrine functions. The exocrine pancreas secretes enzymes and fluids that help neutralize and digest food within the intestines.

Exocrine Pancreas0:41–1:37

The exocrine pancreas can be divided into lobules, each of which contain lots of functional units called an acinus. An acinus is a cluster of acinar cells that all work together to make digestive enzymes.
In fact, the word “acinus” means “berry” which describes the berry-like appearance of these cell clusters. Each acinus secretes digestive enzymes which flow into small intercalated ducts that are lined by ductal cells.
These ductal cells secrete bicarbonate and fluids that make up the liquid portion of pancreatic fluid, and ultimately help to neutralize the acidic stomach contents as they enter the intestines.
The intercalated ducts merge together forming an intralobular duct which join with other interlobular duct, and finally drain into the main pancreatic duct.
The main pancreatic duct travels through the length of the pancreas and drains into the duodenum. Now let’s look at the enzymes made by the acinar cells.

Enzymes1:37–4:53

The main enzymes include pancreatic amylase which breaks down carbohydrates; trypsin and chymotrypsin, which break down proteins; and lipase which break down lipids.
Now as it turns out, macromolecules like carbohydrates, proteins, and lipids are also found in the cells of the pancreas.
Thus, in order protect the pancreas from destroying itself, the acinar cells manufacture inactive forms of the enzymes called proenzymes, or zymogens.
These zymogens need to be activated by proteases, which cleave off a polypeptide chain, kind of like pulling the pin on a grenade.
For additional security, the zymogens are kept away from sensitive organelles in storage vesicles called zymogen granules, and are packaged with protease inhibitors that prevent enzymes from doing damage if they become prematurely active.
To digest a meal, these zymogens are released into the pancreatic duct, and delivered to the small intestine where they are activated by the protease trypsin.
Trypsin is a pancreatic digestive enzyme that is initially produced as the zymogen trypsinogen. Normally, trypsinogen isn’t activated until it is cleaved by protease enteropeptidase which is found in the duodenum.
Now, two enzymes that don’t need activation by the protease trypsin, are pancreatic lipase and amylase - both of which are secreted in their active forms.
Now, the secretions of the ductal cells are filled with various ions, particularly sodium, potassium, chloride, and bicarbonate.
The concentrations of sodium and potassium are about the same as the concentrations in the plasma, whereas the concentrations of chloride and bicarbonate depend on the pancreatic flow rate, which is the volume of secretions per minute.
The chloride and bicarbonate concentration is regulated by transport channels on ductal cells. On the apical membrane, which is the side of the ductal cell facing the duct, there is a chloride-bicarbonate exchanger.
And on the basolateral side of the membrane, or the side facing the extracellular fluid, there are both sodium-potassium ATPases and sodium-hydrogen exchangers.
Within the pancreatic ductal cell, the enzyme carbonic anhydrase combines carbon dioxide and water into carbonic acid. Carbonic acid then dissociates into bicarbonate and hydrogen.
The hydrogen ion is pumped out of the ductal cell and into the blood in exchange for a sodium ion via the sodium-hydrogen pump, and bicarbonate ion is pumped into the pancreatic duct, becoming part of the pancreatic fluid, in exchange for a chloride ion.
When food is being digested in the intestines, the concentration of bicarbonate in the pancreatic fluid has to be high to offset the acidity of the stomach acid.
Consequently, the chloride concentration in the pancreatic fluid will be low since the chloride ions are being exchanged for bicarbonate ions.
So when the pancreas increases secretion, which increases the flow rate, the bicarbonate concentration increases and the chloride concentration decreases.
Now, there are three phases of pancreatic fluid secretion: the cephalic, gastric, and intestinal phases. Let’s say you’re about to eat a nice, big slice of pizza.

Secretion Phases4:53–6:51

In the cephalic phase, the sight and smell of the pizza reaches the brain and causes it to send efferent signals through the vagus nerve to the pancreas.
The vagus nerve secretes the neurotransmitter acetylcholine which stimulates muscarinic receptors on acinar cells and causes them to secrete enzymatic fluid.
Next, is the gastric phase, which is when the chewed up pizza enters the stomach and makes it distend. Distention is sensed by mechanoreceptors in the stomach wall.
This afferent information travels through the vagus nerve to the brain which sends efferent signals back through the vagus nerve to the pancreas.
The result is that the acinar cells produce slightly more fluid. Finally, there’s the intestinal phase which is responsible for over 80% of pancreatic secretions.
When chyme, or partly digested food and stomach acid, enters the duodenum in the intestinal phase, proteins and lipids are broken down into various components such as amino acids and fatty acids by pancreatic enzymes that gets produced in cephalic and gastric phases.
These amino acids and fatty acids stimulate I-cells which are in the lining of the duodenum and jejunum. I-cells secrete the hormone cholecystokinin or CCK, which binds to receptors on the acinar cells of the pancreas and strongly stimulates them to increase secretion of digestive enzymes.
Chemoreceptors in the intestinal mucosa can also detect the presence of lipids, carbohydrates, proteins, as well as decreases in pH in the lumen.
These chemoreceptors send afferent information to the brain via the vagus nerve and efferent information comes back to the pancreas back through the vagus nerve to increase pancreatic secretion during the intestinal phase.

Hormonal Regulation6:51–7:43

Similar to the acinar cells, ductal cells also have cholecystokinin and acetylcholine receptors. In addition, ductal cells have receptors for a hormone called secretin which is released during the intestinal phase.
Partially digested food arriving from the stomach is acidic and when it enters the duodenum, the rise in acidity signals S cells that line the duodenum to release secretin.
Secretin acts on secretin receptors on the ductal cells to massively increase secretion of the aqueous portion of the pancreatic fluid which is high in bicarbonate, and therefore helps to neutralize the acidic chyme.
When food eventually reaches the the ileum and colon, neuroendocrine cells secrete the hormone peptide YY which help inhibit pancreatic secretion.
Although the exact mechanism is not well understood. Alright, as a quick recap...acinar cells of the pancreas produce enzymes that help digest food and ductal cells produce aqueous secretions that help neutralize the acidic stomach contents.

Review7:43–8:16

Acinar cells are mainly stimulated by cholecystokinin and the neurotransmitter acetylcholine, whereas ductal cells are mainly stimulated by secretin.
Finally, the concentration of sodium and potassium in pancreatic secretions is relatively constant, but the concentration of bicarbonate increases when there’s a higher demand for acid neutralization.