GI Endocrinology

Question 1

What happens to chyme following food digestion in the stomach?

Answer 1

• Enters duodenum
• Acidic - remains mixed with acid arriving from stomach

Question 2

How do S cells respond to acid?

Answer 2

• Found in duodenal mucosa
• Respond by secretion of secretin

Question 3

How does secretin increase bicarbonate production and why does it do this?

Answer 3

• Bind to secretin receptors on basolateral membrane of ductal cells
• Release bicarbonate into pancreatic ducts
• Bicarbonates neutralises acid - pancreatic enzymes require neutal pH

Question 4

Describe the role of concentration gradients in pancreatic function.

Answer 4

• Apical surface of ductal cells have CFTR channels - move chloride against concentration gradient
• Used by SLC26 - move down concentration gradient in exchange for HCO3-
• Increase in HCO3- leads to osmotic movement of water through aquaporins - thins pancreatic secretions and passes enzymes into duodenum

Question 5

What are the consequences of cystic fibrosis?

Answer 5

• Reduced bicarbonate production and thicker pancreatic secretions
• Secretions blocked in pancreas, fewer enzymes reach duodenum and acid not neutralised effectively (any enzymes are denatured)
• Reduced absorption and digestion

Question 6

How does secretin affect the antral G and D cells?

Answer 6

• Inhibits gastrin secretion from G cells
• Stimulates somatostatin release from D cells

Question 7

Describe how CCK stimulates bile release from gall bladder.

Answer 7

• When released, CCK enters the circulation - Stimulates smooth muscle cells in gallbladder to contract
• Stimulates the contraction of gallbladder and bile release into duodenum

Question 8

How does secretin affect the gall bladder?

Answer 8

• Release bicarbonates into bile duct - protective function - protects cholangiocytes from bile acid induced damage
• Affected in CF - protective barrier lost

Question 9

CCK can act on the stomach to slow gastric emptying. Why might this be advantageous?

Answer 9

• Allows release of pancreatic enzymes into the duodenum in advance of the presence of nutrients

Question 10

How does CCK induce its appetite suppressive effect?

Answer 10

• Modulates sensitivity of vagus nerve to satiety hormones
• WHEN HUNGRY - vagus nerve expresses neuropeptides (to signal hunger to CNS) and receptors for hunger hormones
• WHEN FED - reduced expression.
• Transition from hungry to fed state mediated by CCK

Question 11

Describe GLP-1.

Answer 11

• Released by L-cells in response to carbohydrate, fat and protein ingestion, as well as vagal stimulation
• Incretion - stimulates insulin secretion
• Binds to GLP-1 receptors on pancreatic beta cells - causes rise in intracellular calcium. Induces insulin release

Question 12

There are some GLP-1 neurons in the NTS. How does this work?

Answer 12

• Receives inputs from visceral sensory neurons
• In response to certain signals, release GLP-1 to various regions of CNS

Question 13

What makes GLP-1 an ideal candidate as a drug target for obesity?

Answer 13

• Incretin effects
• Inhibits hunger
• Induces weight loss

Question 14

Describe ghrelin.

Answer 14

• ‘Hunger hormone’
• Released by X/A cells in fundus - likely in response to sympathetic stimulation
• Fluctuate during the day but peak before mealtimes

Question 15

What is the neural mechanism by which ghrelin increases food intake?

Answer 15

• Area of hypothalamus known as arcuate nucleus - regulator of feeding behaviour. Contains POMC and NPY neurons
• POMC neurons signals to PVN - induce satiety when active
• NPY neurons inhibit POMC neurons and induce hunger
• Ghrelin activates NPY neurons

Question 16

VSG is a surgical procedure in which a significant portion of the stomach is removed. This leads to significant weight loss in patients with obesity. Suggest why.

Answer 16

• Removal of fundus - removal of X/A ghrelin secreting hormones - reduction in ghrelin
• Smaller stomach volume