#Pancreatic secretions

#Describe pancreatic secretions and their regulation

#Exocrine secretions

Cells that contribute to exocrine pancreatic functions account for 90% of pancreatic mass, producing 1500 ml of secretions each day.

#Bicarbonate

Secreted into the pancreatic ducts by ductal cells, so called because they line the pancreatic ducts.

Mechanism:

• Within the cell, bicarbonate is formed via carbonic anhydrase:
  • $\text{CO}_2 + \text{H}_2\text{O} \space \space \underrightarrow{\text{carbonic anhydrase}} \space \space \text{HCO}_3^- + \text{H}^+$
• Chloride is secreted into the lumen by CFTR channels.
• Chloride is returned to the cell in exchange for bicarbonate by chloride-bicarbonate exchangers.
• The net effect is movement of bicarbonate into the lumen.

Luminal concentration: 30–150 mmol/L

Function:

• Alkalinises pancreatic secretions.
• Neutralises gastric acid entering the duodenum.
• Protects the duodenal mucosa.
• Provides optimal pH for digestive enzyme activity.

#Digestive Enzymes

Secreted by acinar cells via exocytosis, so called because they line the pancreatic acini — the bulbous areas that serve as the beginning of the pancreatic ducts.

Function: enzymes break down macronutrients to facilitate absorption.

• Amylase breaks down carbohydrates
• Lipase breaks down fats
• Proteases (trypsin, chymotripsin) break down proteins

#Regulation of exocrine secretions

Phase	Events
Cephalic phase	~20% of total pancreatic secretion Triggered by sight, smell, and anticipation of food Mediated by vagal stimulation (acetylcholine): Predominantly stimulates acinar cells Minor stimulation of ductal cells
Gastric phase	~10% of total pancreatic secretion. Gastrin released from gastric G cells in response to: Gastric distension Protein content Vagal stimulation Gastrin stimulates acinar enzyme secretion.
Intestinal phase	~70% of total pancreatic secretion (major regulatory phase) Secretin: Released in response to acid and fat → stimulates ductal bicarbonate secretion Cholecystokinin (CCK): Released in response to fat and protein → stimulates acinar and ductal secretion Somatostatin and pancreatic polypeptide: Inhibit exocrine pancreatic secretions

#Endocrine secretions

#Insulin

Secreted by beta-islet cells.

Stimulated by:

• Hyperglycaemia
• Products of metabolism: ↑ fatty acid, ketone, or amino acid levels
• Hyperkalaemia
• Pancreas: Glucagon
• GI hormones: CCK, gastrin, GLP-1
• Other hormones: cortisol
• Neural: vagal stimulation

Inhibited by

• Hypoglycaemia
• Pancreas: insulin, somatostatin
• Exercise
• Neural: alpha agonism

Effects

• Increased glucose uptake and utilisation by many tissues
• Including hepatic glycogenesis

#Glucagon

Secreted by alpha islet cells.

Stimulated by

• Hypoglycaemia - unclear if a direct effect or via insulin/somatostatin
• Products of metabolism: ↑ amino acid levels
• GI hormones: CCK, gastrin
• Neural: beta-agonism, vagal stimulation

Inhibited by

• Pancreas: insulin, somatostatin
• Products of metabolism: ↑ fatty acid or ketone levels

Effects

• ↑ hepatic glycogenolysis and gluconeogenesis

#Somatostatin

Secreted by:

• Pancreatic δ (delta) cells
• Hypothalamus

Stimulated by:

• Hyperglycaemia
• Amino acid content in blood
• CCK

Inhibited by:

• Vagal stimulation (acetylcholine)

Effects

• Inhibits pancreatic hormones: insulin, glucagon and pancreatic polypeptide
• Inhibits GI hormones: gastrin, secretin and CCK
• Overall, decreases GI motility, secretion and splanchnic blood flow

#Pancreatic polypeptide

Source

• Produced by F cells, located predominantly in the peripheral regions of pancreatic islets

Stimulated by:

• Food intake
• Vagal stimulation
• Exercise

Effects

• Inhibits gastrointestinal motility and GI secretions