Gastric secretion

Question 1

Stomach - function of:

1. Fundus
2. Body
3. Antrum

Answer 1

1. Storage
2. storage, mucus, HCL, pepsinogen, intrinsic factor
3. mixing/grinding & gastrin

Question 2

What is the cellular composition of gastric glands?

Answer 2

Mucus neck cells: mucus
Chief cells: pepsinogen
Parietal cells: HCL & intrinsic factor
Also gastric pits (just above gastric glands) contain surface mucus cells.

Question 3

How is the acidic pH of stomach created?

Answer 3

CO2 from blood goes into parietal cell where Carbonic anhydrase combines it with H2O to form unstable intermediate carbonic acid which dissociate to form H+ & bicarbonate (HCO3). 1 H+ is transported into stomach lumen by H+/K ATPase (1 K+ transported into the cell). At basolateral membrane, bicarbonate transported into blood in exchange for Cl- ion by HCO3/Cl exchange transporter which then through chloride channel transported into stomach lumen. Accumulation of osmotically-active hydrogen ion in the canaliculus generates an osmotic gradient across the membrane that results in outward diffusion of water. H+ & Cl- combine to form HCL. pH of stomach <2. Due to bicarbonate blood pH >7.4 there (slightly elevated to maintain parietal cell pH.
Canaliculus = deep infolding or channel that increases surface area for secretion in gastric parietal cells.

Question 4

What controls gastric acid secretion?

Answer 4

Neurocrine: Vagus/local refluxes
Endocrine: gastrin
Paracrine: histamine

Question 5

Explain the mechanism behind gastric acid secretion before you have even swallowed food.

Answer 5

Cephalic phase: Sight, smell, taste of food stimulate vagus nerve which releases ACh that then binds to muscarinic cholinergic receptors on parietal cells. These increase intracellular Ca levels which activates protein kinase C. Vagus nerve also stimulates G cells (found in antrum) to produce gastrin which binds to it receptor on basolateral surface of parietal cell & do what ACh does.
Gastrin/ACh stimulate enterochromaffin-like cells (ECL) to produce histamine which enters cell through H2 receptor. There it activates adenylate cyclase that increases AMP conc intracellularly which leads to PKA activation. PKA phosphorylates cytoskeletal proteins involved in transport of the H+/K+ ATPase from cytoplasm to plasma membrane.

Question 6

What effect prostaglandins have on gastric acid secretion?

Answer 6

Decreases it. It receptor on parietal cell is coupled to inhibitory G protein that switches off adenylate cyclase thus reducing AMP & proton pump activity.

Question 7

Explain the mechanism behind gastric acid secretion after you have swallowed food.

Answer 7

Gastric phase: Distension of stomach on arrival of food stimulates vagal/enteric reflexes that release ACh which activates parietal cells. Peptides in lumen act on G cell that release gastrin which also activates parietal cells. Gastrin/ACh then stimulates ECL cells to release histamine which also activates Parietal cells.

Question 8

Describe the mechanism behind inhibiting gastric acid secretion.

Answer 8

• Cephalic phase: stopping eating decreases vagal activity.
• Gastric phase: decrease in pH (increase in HCl conc) decreases gastrin.
• Intestinal phase: acid in duodenum activates enterogastric (splanchnic) reflex & stimulates secretin release. Both of these decreases gastrin secretion & effect of gastrin stimulation of parietal cells. Fat/CHO in duodenum stimulate GIP (gastric inhibitory peptide - hormone) release which decreases gastrin secretion & parietal HCl secretion.

Question 9

What are enterogastrones and what is their purpose?

Answer 9

Hormones released in response to acid, hypertonic solutions, fatty acids or monoglycerides in duodenum from gland cells in duodenal mucosa - secretin, cholecystokinin (CCK), GIP.
Act collectively to prevent further acid build up in duodenum via 2 strategies:
- inhibit gastric acid secretion
- reduce gastric emptying (inhibit motility/contract pyloric sphincter).

Question 10

1. Define zymogen.

2. What is the function of zymogen?

Answer 10

1. Inactive precursor of active enzyme.

2. Zymogen storage prevents cellular digestion.

Question 11

1. What is pepsinogen and where is it secreted from?

2. Name the active form of pepsinogen & the conditions under its released?

Answer 11

1. A zymogen secreted by Chief cells.
2. Pepsin. Pepsinogen is converted to pepsin when low pH (< 3). Pepsin inactivated at neutral pH (can be converted back to pepsinogen).

Question 12

Gastric mucus is produced by which cells?

Answer 12

Surface epithelial & mucus neck cells.

Question 13

What is the role of mucus?

Answer 13

Cytoprotective role: protects mucosal surface from mechanical injury. Mucus has bicarbonate component which neutralises pH: protects against gastric acid corrosion & pepsin digestion (pepsin would digest stomach protein etc but at neutral pH it is inactivated.

Question 14

Intrinsic factor:

1. is produced by?
2. required for?
3. where is it absorbed from?
4. What happens if you have any defect?

Answer 14

1. Parietal cells
2. vitamin B12 absorption
3. intrinsic factor/B12 complex absorbed from ileum
4. Pernicious Anaemia results (failure of erythrocyte maturation).