Role of Pancreas in Digestion

The pancreas has both exocrine and endocrine portions.
Exocrine portion: secretes pancreatic juice into the duodenum via the pancreatic duct.
Endocrine portion: consists of pancreatic islets (islets of Langerhans) that secrete hormones into the blood.

The exocrine portion secretes pancreatic juice, which enters the duodenum through the pancreatic duct.
The pancreatic duct merges with the common bile duct from the liver and gallbladder, forming the ampulla of Vater (hepatopancreatic ampulla).
The ampulla of Vater opens into the duodenum lumen.
The sphincter of Oddi, a smooth muscle structure, regulates the passage of pancreatic juice and bile through the ampulla of Vater into the duodenum.

The endocrine portion consists of clusters of cells called pancreatic islets (islets of Langerhans).
These cells secrete four main hormones:
- Insulin
- Glucagon
- Somatostatin
- Pancreatic polypeptide
These hormones are released directly into the bloodstream.

Pancreatic glands secrete pancreatic juice.
Each gland contains acinar cells and duct cells.
Acinar cells: secrete digestive enzymes.
Duct cells: secrete bicarbonates.
Pancreatic enzymes digest carbohydrates, fats, proteins, and nucleic acids.
Bicarbonates neutralize hydrochloric acid entering the small intestine from the stomach.

Primary pancreatic secretion formed in the acinus is isotonic and has an ionic composition similar to blood plasma.
In the ducts, the pancreatic juice is enriched with bicarbonates and remains isotonic.

Pancreatic duct cells take up $CO<em>2$ from the blood to generate carbonic acid ( $H</em>2CO_3$ ).
Carbonic acid dissociates into bicarbonate ( $HCO_3^-$ ) and $H^+$ .
Bicarbonate is secreted into the lumen of the duct via the $HCO_3^-$ / $Cl^-$ exchanger.
$Cl^-$ delivered into the duct cell passively leaks back through the CFTR chloride channel (cystic fibrosis transmembrane conductance regulator channel).
$H^+$ is removed from the cell by the $Na^+$ / $H^+$ exchanger.

Pancreatic juice has higher concentrations of bicarbonate and lower concentrations of chloride compared to blood plasma.
$Na^+$ and $K^+$ concentrations are similar to those in blood plasma.
As the secretion rate increases, the pancreatic juice contains more bicarbonate and becomes more alkaline.
With increasing secretion rate, $Cl^-$ concentration decreases because bicarbonate is secreted into the lumen in exchange for $Cl^-$ delivery into the ductal cells.
$Na^+$ and $K^+$ concentrations do not change with variations in the secretion rate.

The pancreas produces about 1 liter of pancreatic juice per day.
Pancreatic juice is rich in bicarbonate, giving it an alkaline pH of 7.1-8.2.
The alkaline pH buffers gastric acid in chyme, which is emptied into the duodenum from the stomach.
This action of buffering stops pepsin activity and creates an appropriate pH for the action of digestive enzymes in the small intestine.

Protein-digesting enzymes (proteases): trypsin, chymotrypsin, carboxypeptidase, aminopeptidase, elastase.
Carbohydrate-digesting enzyme: amylase.
Triglyceride-digesting enzymes: lipase, phospholipase A2, cholesterol ester hydrolase.
Nucleic acid-digesting enzymes (nucleases): ribonuclease, deoxyribonuclease.

Proteases are initially secreted in inactive forms (zymogens) to prevent autodigestion of the pancreas.
Trypsinogen (inactive) is converted to trypsin (active) in the duodenum lumen by enterokinase.
Once trypsin is formed, it activates other zymogens:
- Chymotrypsinogen → Chymotrypsin
- Proelastase → Elastase
- Procarboxypeptidase → Carboxypeptidase

Endopeptidases: trypsin, chymotrypsin, elastase (digest internal peptide bonds).
Exopeptidases: carboxypeptidase and aminopeptidase (digest terminal peptide bonds).

Amylase (secreted in active form) splits starch into oligosaccharides, trisaccharides, and disaccharides.

Lipase: converts lipids to monoglycerides and free fatty acids (secreted in active form).
Cholesterol ester hydrolase: converts cholesterol ester to free cholesterol and fatty acids (secreted in active form).
Phospholipase A2: converts phospholipids to lysolecithin and fatty acids (secreted in inactive form, activated by trypsin).

Bile salts emulsify large lipid globules into smaller ones, increasing the surface area for lipase action.
Lipase can be inactivated by bile salts; colipase binds to both bile acids and lipase, bringing lipase back to the surface of the lipid droplet.
Colipase acts as a cofactor for lipase.

Hormonal regulation: secretin, CCK, and gastrin.
Neural regulation: sympathetic and parasympathetic fibers of the autonomic nervous system (ANS).

Secretin:
- Released from S cells in the duodenal mucosa in response to acid in the duodenal lumen.
- Stimulates pancreatic duct cells to secrete bicarbonate-rich fluid.
Cholecystokinin (CCK):
- Released from I cells in the duodenal mucosa in response to fatty acids, dipeptides, and tripeptides.
- Stimulates pancreatic acinar cells to secrete digestive enzymes.
Gastrin:
- Stimulates the secretion of enzymes in pancreatic acinar cells, acting via the same receptor as cholecystokinin.

Sympathetic fibers:
- Originate in the thoracic spinal cord.
- Postganglionic neurons are located in the celiac and superior mesenteric plexuses.
- Generally inhibit pancreatic secretion.
Parasympathetic fibers:
- Originate in vagal nuclei in the medulla.
- Postganglionic neurons are located in the enteric nervous system.
- Stimulate pancreatic secretion.
Vagus nerve stimulation increases the release of pancreatic enzymes, similar to the effect of CCK.

Cephalic phase:
- Triggered by the thought, sight, smell, and taste of food.
- Mediated by the vagus nerve.
- Results in the release of pancreatic enzymes.
Gastric phase:
- Triggered by mechanical and chemical stimulation of the gastric mucosa when food enters the stomach.
- Mediated by neural (vagal stimulation) and hormonal (gastrin release) mechanisms.
- Increases the release of enzymes in the acinus of the pancreatic gland.
Intestinal phase:
- Triggered by mechanical and chemical stimulation of the duodenal mucosa when gastric content enters the duodenum.
- Mediated by neural (vagal stimulation) and hormonal (secretin and CCK release) mechanisms.
- Vagal stimulation and CCK increase the release of enzymes, and secretin stimulates the secretion of bicarbonates.
The intestinal phase is the most important, producing about 80% of the total pancreatic secretion after a meal.