GI Secretion

Question 1

List the functions of secreted gastric acid.

Answer 1

1. Kills bacteria (disinfects food at pH 1.0)
2. Begins protein digestion - denatures proteins and activates pepsinogen (active form = pepsin)
3. Acid producing parietal cells also secrete intrinsic factor when secreting acid (vitamin B12 absorption)
4. Energy consuming process – H+/K+ ATPASE pumps across the luminal surface against a significant gradient

Question 2

Describe the protective mechanisms in place to limit toxicity of gastric acid, including occasions where these processes might be disrupted.

Answer 2

• HCl secretion is risky, so the body has mechanisms in place to confine acidity to the stomach as much as possible
• Mucus layer and alkaline (HCO3-) layer at the cell surface (surface mucus cells) protects the stomach lining – prostaglandins can increase mucus production
• Tight junctions between cells prevent acid from infiltrating the layers of the wall
• Rapid cell turnover maintains surface integrity

Question 3

Discuss the modulation of gastric acid secretion throughout the day and night.

Answer 3

1. Basal Phase: follows circadian rhythm. Low acid secretion in the morning before awakening and highest in the evening.
2. Cephalic Phase: primarily mediated by the vagus nerve. Stimulation of the vagus nerve results in (1) release of ACh; (2) triggering of the histamine release from ECL cells; (3) release of gastrin-releasing peptide (GRP) from the vagal and enteric neurons (ENS); and (4) inhibition of somatostatin release from the delta cells (D cells) in the stomach. The cephalic phase accounts for 30% of total acid secretion.
3. Gastric Phase: Initiated by entry of food into stomach. The bolus of food distends gastric mucosa, activating the vagovagal reflex and local ENS reflexes. Additionally, partially digested protein stimulates release of gastrin from antral gastrin cells. Gastrin enters circulation and acts on parietal cells and ECL cells in the stomach to increase acid secretion.
4. Intestinal Phase: Partially digested peptides in the duodenum causes gastrin secretion from duodenal gastrin cells. Gastrin enters circulation and acts on parietal cells and ECL cells in the stomach to increase acid secretion.

Question 4

Describe the mechanism of gastric acid generation and secretion, including the role of K+, Cl‑/HCO3, carbonic anhydrase and H+-K+ ATPase.

(This answer is a long one…. feel free to shorten it)

Answer 4

Gastric acid production occurs in parietal cells of oxyntic glands. Protons are obtained from water, as it exists in equilibrium with H+ and OH ions. HCO3 production consumes OH ions, increasing the number of available hydrogen ions. Carbonic anhydrase (CA) is required for this to happen as CA uses CO2 from the blood and OH ions from water to form HCO3, with H+ ions as a byproduct. Hydrogen ions are actively transported across the apical (luminal) membrane by exchange for K ions via the H/K ATPase, a mechanism of primary active transport. Protons are pumped out of the cell against their concentration gradient, but loss of protons form parietal cells also causes HCO3 concentration to rise. HCO3 is transported down its concentration gradient at the basolaterla membrane in exchange for Cl ions moving into the cell against their electrochemical gradient. This is secondary active transport. The Cl which accumulates in the cell is transported across the apical membrane into the lumen by passive, facilitated diffusion.

The net reaction is that HCl is transported into the lumen and water follows for osmotic reasons, moving from blood into the stomach via transcellular mechanism. A secondary result of acid secretion is the venous blood leaving is high because increased HCO3 transport. This is called the alkaline tide.

Question 5

Describe the protective barrier of the gastric surface.

Answer 5

The mucosal barrier is composed of surface epithelial cells, mucous and HCO3. Mucous is secreted from specialized mucous neck cells (in the glands) and surface goblet cells in the epithelial layer. Mucous forms a gelatinous layer which traps water and HCO3 so acid that diffuses in is neutralized. This layer also prevents the dissipation of the pH gradient from the gastric lumen to the blood.

Question 6

Describe the role of the stomach, if any, on the gastric digestion of carbohydrates, proteins, and fats.

Answer 6

Carbodydrates: Amylase, secreted by salivary glands, digests starches in the mouth and stomach, producing polysaccharides

Proteins: Pepsin, secreted by the stomach, digests protein in the stomach, producing polypeptides

Fats: Lingual lipase secreted by serous glands of toungue digests fat in mouth and stomach, producing monoglycerides and fatty acids

Question 7

In general terms, describe how the three parietal cell secretagogues induce acid secretion.

Answer 7

1. Acetylcholine (ACh): bind muscarinic receptors on the basolateral membrane of parietal cells which activates a G protein coupled receptor (GPCR). This causes an increase in intracellular calcium.
2. Gastrin: causes a rise of intracellular calcium
3. Histamine: binds H2 receptors that activate a G protein which turns on adenylate cyclase that in turn synthesizes cAMP