Regulation and Disorders of Gastric Acid Secretion

Question 1

The stomach is composed of the fundus, the body and the antrum. List the components secreted by the antrum and the body of the stomach.

Answer 1

Body: mucus, pepsinogen and HCl
Antrum: mucus, gastrin, pepsinogen (some HCl, but not as much as that secreted by the body of the stomach

Question 2

As part of the formation of hydrochloric acid (HCl) within the stomach lumen, there is secondary active transport which exchanges HCO3- for Cl- (i.e., Cl- comes into the parietal cell while HCO3- leaves it). The Cl- later leaves the parietal cell into the stomach lumen via Cl- channel and this Cl- later binds with H+ (pumped by the K+/H+ ATPase pump) to form HCl. Which of the following best describe the active transport which exchanges Cl- for HCO3-?

Answer 2

Cl- shift

Question 3

From the previous question (Q2), it is clear that parietal cells form the components of HCl separately. What is the reason for this?

Answer 3

HCl serves a useful purpose in the cell, but it has damaging effects; this is why its components (H+ and Cl-) are produced separately and transported to the gastric gland.

Question 4

How does the activity of K+/H+ ATPase pump contribute to the formation of HCl?

Answer 4

It actively exchanges K+ for H+. This means that K+ goes in and H+ goes out into the gastric glands. This H+ is then able to react with Cl- to form HCl, as Cl- is already being extruded via the Cl- channel into the gastric lumen.

Question 5

Acid secretion is finely controlled in the stomach. List 3 regulators of acid secretion in the stomach and briefly describe the mechanism of control exhibited by each regulator.

Answer 5

Cephalic phase: sight smell, etc.; stimulation of parasympathetic activity – ACh secretion; ACh→ histamine release from ECL; histamine +H2 receptor → acid secretion
Gastric phase: presence of food/food components in the stomach (distension → provocation of vago-vagal and local reflexes → amplification of secretion). Presence of peptide→ gastrin release (gastrin has both histaminergic effects (i.e. stimulates histamine release) and also has direct effects on parietal cells) both effects cause HCl secretion form parietal cells –parietal cells are highly specialised to secrete concentrated HCl.
Intestinal phase: balances acid secretion with digestion and absorption of nutrients: ↑ acidity causes inhibits acid secretion – if acid secretion is not inhibited, the digestive enzymes will not work. Therefore, there is reflex inhibition of acid secretion as soon as chyme enters the duodenum to allow enzyme to act on the chyme → digestion and absorption of micronutrients

Question 6

Which of the following is the most important promoter for the conversion of pepsinogen to pepsin?

Answer 6

HCl

Question 7

Mrs Jyamundi presented with painful arthritis which she says bothers her every winter for the last 10-15 years. Her GP often proscribes her 2x300mg aspirin to be taken with food. The Dr advised her to be careful of the side effects of aspirin. Which of the following does not adequately explain the mode of action of aspirin and or its side effects?

Answer 7

It inhibits the lipoxygenase pathway which can increase the levels of leukotrienes which can cause severe asthmatic attacks

Question 8

Which of the following is secreted by parietal cells and important for the absorption of Vitamin B12?

Answer 8

Intrinsic factor

Question 9

The figure below depicts the factors that influence HCl secretion in the stomach at the gastric phase. Identify the following depicted in the diagram.

Substance 1:
Substance 2:
Substance 3:
Substance 4:
Substance 5:

(ref to diagram on canvas)

Answer 9

Substance 1: peptide, amino acids

Substance 2: gastrin

Substance 3: histamine

Substance 4: acetylcholine (ACh)

Substance 5: somatostatin

Question 10

Which of the following best describes the 3 stages of acid secretion by parietal cells?

Answer 10

cephalic
gastric
intestinal

Question 11

Name 3 principal stimuli (triggers) of HCl (gastric acid) secretion

Answer 11

Mention of any of the following is correct:

Acetylcholine due to increased parasympathetic activity of nerves to stomach
Gastrin - due to increased parasympathetic activity of nerves to stomach
Histamine - due to increased parasympathetic activity of nerves to stomach
Food components, e.g. proteins and peptides

Question 12

Which of the following is the most likely inactivator of pepsin?

Answer 12

Food in the stomach

Question 13

Which of the following is an enterogasterone?

Answer 13

CCK

Question 14

Which one of the following cells is thought to be a major target for the damaging effects of Helicobacter pylori and is implicated in the pathogenesis of duodenal ulceration?

Answer 14

D- and G-cells

Question 15

Some thoughts on the effects of H. pylori of the cells listed in the previous question (Q14)

Answer 15

Accelerates the proliferation of acinar cells
Decreases crypt cell density
G (increased) and D cells (decreased)
G cells (decreased) D cells (increased)
Negatively regulates oxyntic cell

Question 16

A man presents with burning feeling in the throat and chest, with difficulty of swallowing. Investigations have shown that he suffers with gastro-oesophageal reflux disease for which he was prescribed an H2-receptor antagonist. Which of the following is a H2 receptor antagonist?

Answer 16

Cimetidine

Question 17

The stomach contents are exposed to the high concentration of hydrochloric acid (~150mM), which has the potential to damage the gut mucosa. List and provide brief descriptions of the factors that prevent the stomach from digesting itself?

Answer 17

Secretion of HCO3-: This helps to increase pH (neutralises HCl); pepsin become less active →decreased degradation of mucus
Mucus – forms a thick slimy layer over luminal surface; mucus (thick and sticky – forms water-insoluble gel on epithelial surface of gut lumen →↓H+ flow) forms a barrier against the damaging effects of HCl.
Surface membrane of mucosal cells have tight junctions between epithelial cells lining the stomach helps to restrict the diffusion of H+ into the underlying tissue
The damaged epithelial cells are replaced by new cells every few days
PGE2 and PGI2 can inhibit acid secretion by enhancing blood flow to mucosa – this encourages mucus production- see above for beneficial effects of mucus
Protein content of the food will neutralise the acid
Trefoil proteins – a family of proteins synthesised by goblet cells and secreted on apical gastrointestinal mucosa → protection and healing if damage occurs

Question 18

What is the main function of lipase?

Answer 18

Acts on triglycerides → fatty acids and glycerol

Question 19

Mr Phatty went to see his GP complaining of severe heart burn, epigastric pain, and vomiting blood. He explained to his Dr that all of his symptoms not relieved by regular doses of the H2 receptor antagonist, ranitidine and the antacid gaviscone liquid. Following a urea breath test, he was diagnosed as having Helicobacter pylori. His GP put him on triple therapy to help clear the infection and explained to him that he must comply with the treatment as the bacteria have many virulence factors which can help it to survive in the gut. The following are virulence factors of pylori, except

Answer 19

Acidity regulator (claspase A1)

Question 20

List 3 important aggravators of ulcers

Answer 20

H. pylori infection
Large meals, regurgitated bile acids
NSAIDs, e.g., aspirin
Chronic gastritis
Genetics (blood group O, having close family with ulcer); being male)
Smoking, alcohol, spicy foods

Question 21

List two mechanisms that can cause peptic ulcer to form and provide a very brief description of each

Answer 21

Breakage of mucosal barrier – This results in an imbalance between protective and damaging factors. If there is a greater presence of the damaging factors – the damaging factors will expose the epithelial cells membrane. When this is exposed, pepsin and HCl will directly be able to access the epithelial membrane (as there no now thick mucus gel acting as a barrier) → a crater will be created in the gut → ulcer (bleeding, haemorrhage will occur). NSAIDs (e.g. aspirin), less production of PGE2 and PGI2 can affect the restitution (aspirin) of the gut, mucosal blood flow and mucus secretion (PGE2 and PGI2 effects). H. pylori will damage the gut mucosa, causing direct exposure of the epithelial cells
Exposure of tissues to the erosive effects of HCl and pepsin: HCl and pepsin have very damaging effects on the gut; if the gut tissue is exposed to it for long enough, especially in a situation where there is breakage of mucosal barrier and less HCO3- and mucus secretion, this will lead to ulcer.

Question 22

H. pylori is an important risk factor for ulcers. Which of the following tests can be used to diagnose an individual who is suspected of having the H. pylori?

Answer 22

Urease test