GIS09 Gastroduodenal Secretions And Control

Question 1

Gastric secretions from the stomach

Answer 1

3 regions:
1. Fundus

2. Body
   - mucus
   - pepsinogen
   * **- HCl
3. Antrum
   - mucus
   - pepsinogen
   * **- gastrin

Other secretions:

• histamine
• HCO3
• intrinsic factor

Question 2

Secretory cells in stomach

Answer 2

1. Surface mucous cells:
   - mucus
   - HCO3
2. Mucous neck cells:
   - thin mucus
   - pepsinogen
3. **Chief / peptic cells:
   - **pepsinogen
4. ***Parietal / Oxyntic cells:
   - HCl
   - intrinsic factor
5. ***Enterochromaffin like (ECL) cells:
   - Histamine
6. ***G-cells (enteroendocrine cells; mainly in pyloric glands):
   - Gastrin
7. D-cells:
   - Somatostatin

Question 3

Gastric secretions in stomach

Answer 3

Proximal: Oxyntic gland mucosa

• **- Parietal cells —> HCl, intrinsic factor
• Chief cells —> pepsinogen
• Mucous neck cells —> mucus, pepsinogen

Distal: Pyloric gland mucosa

• **- NO parietal cells
• **- G-cells —> gastrin
• Chief cells —> small amount of pepsinogen
• Mucous cells —> mucus, HCO3

Question 4

Gastric acid content

Answer 4

Cations:
H (pH: 1.0), Na, K, Mg

Anions:
Cl, HPO4, SO4

Question 5

Gastric acid function

Answer 5

1. Provide optimal pH for pepsin
2. Convert pepsinogen to pepsin
3. Denature ingested protein
4. Break up CT (e.g. collagen) of meat
5. Kill bacteria

Question 6

Gastric acid secretion mechanism by Parietal cells

Answer 6

1. H/K-ATPase active transport: pump H+ into stomach lumen in exchange of K+
   —> ***H+ into lumen, K+ into cell
   —> K+ exit back into lumen down electrochemical gradient
2. Carbonic anhydrase: CO2 —> H2CO3 —> ***H+ (pump into stomach) and HCO3- (exchange for Cl-)
3. HCO3 enter capillary on opposite side in exchange of Cl- through antiporter
   —> ***HCO3 into capillary, Cl into cell
   —> Cl- exit into lumen down electrochemical gradient

Question 7

Ionic composition of gastric juice and secretion rate

Answer 7

• Gastric juice is ***isotonic to plasma at all rates (pH <1 to ~3)

***- Ionic composition varies with rate of gastric secretion

• Basal rate (low / non-stimulated rate): ***primarily NaCl with small amount of H and K
• Basal rate ***greater in evening, lowest in morning
• ***[H+], [Cl-] ↑ with ↑ secretion rate

Question 8

Control of gastrointestinal secretion

Answer 8

Neural regulation (Neurocrine: using neurotransmitter)
- Short reflex (Enteric NS)
- Long reflex (ANS)
—> Parasympathetic (Vagus: ↑ peristalsis, ↑ blood flow, ↑ absorption, ↑ secretion)
—> Sympathetic (↓ peristalsis, ↓ blood flow, ↓ absorption, ↓ secretion)

Chemical regulation

• Endocrine
• Paracrine

Question 9

***Control of HCl secretion by parietal cells

Answer 9

4 chemical factors regulating insertion of H/K-ATPase on apical membrane of parietal cells (more inserted, more H pumped into stomach —> acid secretion ↑)

1. Gastrin (hormone from G cell)
   - **↑ intracellular [Ca] of parietal cells
   - stimulate **histamine release from ECL cells
   - trophic effects: ***↑ size and no. of ECL cells
2. ACh (neurotransmitter from enteric NS) (bind with muscarinic ACh receptor)
   - **↑ intracellular [Ca] of parietal cells by generating second messenger IP3
   - stimulate **histamine release from ECL cells
3. Histamine (paracrine) (from ECL cells)
   - bind with **H2 receptor
   —> activate adenylate cyclase to **↑ cAMP
4. Somatostatin (paracrine)
   - ***Inhibitory

Question 10

***3 phases of control of HCl secretion

Answer 10

1. Cephalic phase (20%)
   - **Chewing, swallowing, taste, smell —> Neural control from brain —> via **Vagus excite ***Enteric NS —> stimulate Parietal, G cell, ECL cell
2. Gastric phase (70%)
   - **Gastric distension —> **Local Enteric + ***Vagovagal reflex —> stimulate Parietal, G cell, ECL cell
   - Peptides and amino acids —> stimulate G cell
3. Intestinal phase (10%, due to some G cell extend from antrum to duodenum)
   - **Duodenal distension —> **Local Enteric + **Vagovagal reflex —> stimulate Parietal, G cell, ECL cell
   - Peptides and amino acids in **blood—> stimulate G cell in **stomach
   - Protein digestion products in **duodenum —> stimulate G cell in ***intestine

記:

• Distension —> Nervous system (Local enteric + Vagovagal reflex) —> stimulate ALL cells
• Amino acids —> stimulate G cell

Question 11

***Inhibition of acid secretion

Answer 11

Gastric phase:
- ***Acid in antrum
—> stimulate D-cells
—> release Somatostatin
—> 1. inhibit G-cells / 2. directly on Parietal cells
—> 1. inhibit meal-stimulated gastrin secretion / 2. inhibit acid secretion

Intestinal phase:
- **Acid, **fat, amino acids, hypertonicity, distension in duodenum

1. Short neural reflex via local enteric neurons —> ↓ gastric emptying
2. Long neural reflex via ANS —> ↓ parasympathetic + ↑ sympathetic efferent —> ↓ gastric emptying
3. ↑ Hormonal secretion of enterogastrones (**Secretin, **CCK, GIP) from duodenum into blood —> ↓ gastric emptying

Question 12

Relationship between gastric pH, volume of gastric contents and secretion rate

Answer 12

• gastric pH ↑ with ↑ volume of gastric contents (protein in meal act as buffer to counter H+ to ↑ pH)
• volume ↑ then after a while secretion rate ↑ —> maximal secretion of acid ~ 1 hour after meal
• secretion rate ↑ —> gastric pH ↓

Question 13

***Secretion of pepsinogen by Chief cells

Answer 13

By Chief cells
—> pepsinogen (to prevent damage by active enzyme) converted to pepsin by HCl
—> pepsin digest **protein to peptides (break internal peptide bond)
—> **acid secretion by parietal cells ↑ —> pepsinogen secretion by chief cells ↑
—> pepsin **accelerate protein digestion (but is **not necessary)

Stimulated by (acid secretion ↑ —> pepsinogen ↑):

• ACh from Vagus / Enteric nerve plexus
• Acid in stomach through Local nerve reflex
• Gastrin
• ***Secretin, CCK (strange)

When gastric acidity <3:
- feedback inhibition:
—> ↓ gastrin production
—> ↓ acid secretion
—> ↓ pepsinogen secretion

Question 14

Secretion of mucus and HCO3

Answer 14

Mucus:

• Mucous neck cells of gastric glands
• Surface mucous (epithelial) cells of stomach + duodenum

HCO3:

• Surface mucous cells ONLY
• ***Adrenergic agonist ↓ HCO3 secretion —> stress ulcer —> acid corrosive action + pepsin digestion

Mucus + HCO3 function:
- physical + alkaline barrier to protect against friction from food, acidic, proteolytic gastric secretion

Question 15

Pharmacological suppression of HCl secretion

Answer 15

H2 receptor blocker

• Cimetidine
• Ranitidine
• Famotidine

PPI
- Omeprazole

Question 16

Secretion of intrinsic factor by Parietal cells

Answer 16

Glycoprotein (Regulation same as acid)
- required for absorption of vitamin B12 at **ileal mucosa —> DNA synthesis and RBC maturation
- absence of intrinsic factor lead to megaloblastic anaemia (RBC larger than normal)
- Pernicious anaemia (autoimmune Ab destruction of parietal cells) / Total gastrectomy
—> lack of intrinsic factor
—> megaloblastic anaemia
—> patient require lifetime injection of B12
- **ONLY gastric function essential for human life

Question 17

Secretion from small intestine

Answer 17

1. Enzymes for digestion of disaccharides, small peptides, lipids
2. Mucus + HCO3 from ***Brunner’s gland of duodenum
3. NaCl into lumen —> water movement by osmosis —> fluid secretion (>1.5L per day) important for nutrient absorption, lubrication of surface to reduce damage by enzymes

Question 18

Secretion from large intestine

Answer 18

1. Mucus: protect intestinal wall, adherent medium for holding faecal matter together
2. ***NO enzyme

Question 19

Summary

Answer 19

G-cell: Gastrin
D-cell: Somatostatin
ECL cell: Histamine
Enterchromaffin cell: 5HT
Duodenum S cells: Secretin
Duodenum I cells: CCK

Parietal cell: Acid
Chief cell: Pepsinogen