Gastric Acid Secretion: Regulation and Disorders

Question 1

Describe the structure of the stomach and its secretions

What are the contents of Gastric acid?

Answer 1

• • Thin-walled fundus and body - mucous, HCl, Pepsinogen
  • Body has Tubular glands - parietal cells secrete HCl and Intrinsic factor
  • Thick-walled antrum - Less HCl and more Gastrin

- Has a fasting PH of 3.0 as it contains:
• Cations: Na, K, Mg, H
• Anions: Cl, Phosphate, Sulphate
• Pepsins - Protein breakdown
• Lipases - TG breakdown
• Intrinsic factor - Vit B12 absorption
• Mucous

Question 2

How is Gastric acid made?

LOOK AT DIAGRAM!

Answer 2

• HCO3/Cl- exchanger on basolateral membrane of stomach cells - decreases acidity of venous blood from stomach
• Excess Cl- moves into the stomach via Cl- channels and K/H ATPase moves H+ out on luminal membrane - H+ binds with Cl- = HCl
• Stomach secretes lots of HCl daily

Question 3

How is gastric acid production regulated?

Answer 3

HCl secretion is regulated by neuronal pathways and duodenal hormones:
o Directly acting on Parietal cells = ↑acid secretion
o Indirectly affecting Gastrin and Histamine secretion = ↑acid secretion

Question 4

Phases involved in the regulation of gastric acid secretion:
1. CEPHALIC Phase

LOOK AT DIAGRAM!

Answer 4

Taste, smell, seeing food - via vagus nerve

Ach release = ↑acid secretion:
• Stimulates Histamine release from ECL cells
• Direct action on Parietal cells for HCl secretion

Question 5

2. GASTRIC Phase

LOOK AT DIAGRAM!

Answer 5

Distension of stomach - via vagus nerve

• Food/Proteins buffer acid, inhibiting Somatostatin release from D-cells
• Peptides stimulate Gastrin release
• Neuronal reflexes = ACh release

Question 6

3. INTESTINAL Phase

LOOK AT DIAGRAM!

Answer 6

Chyme composition/volume

• High acidity of duodenal contents causes reflex inhibition of gastric acid secretion
• Distension of duodenum, Hypertonicity, AA, FA, monosaccharides inhibit acid secretion
• CCK/Secretin, Somatostatin inhibits Histamine secretion from ECL cells

Question 7

What are the functions of Gastric acid?

Answer 7

• Defence against pathogens
• Protein digestion - activates pepsinogen to pepsin
• Stimulation of bile and pancreatic secretion

Question 8

What is a Peptic Ulcer?

Where does it commonly form?

What factors cause damage to lining from acid secretion?

Answer 8

• Breakage of the mucosal barrier - regurgitated bile acids
• Oesophagus, Stomach, Duodenum
• Smoking, Alcohol, NSAIDs, H.Pylori infection

Question 9

What is H. Pylori Infection?

How does it cause mucosal damage?

LOOK AT PICTURE!

Answer 9

• • Major risk factor of peptic ulcer, and is acquired in childhood
  • Highly pathogenic, Gram negative helix aerobic bacterium
• Penetrates gastric mucosa and can withstand the high acidity of the stomach
  o Motility - moves close to epithelium, which has a higher PH
  o Urease activity - converts urea into ammonia and CO2
  o Virulence factors enable the H. Pylori to adhere and colonise at the gastric epithelium - dysregulates gastrin secretion to increase its secretion

Question 10

What is the role of NSAIDs with H.Pylori?

Answer 10

In normal cells, PROSTOGLANDINS INHIBIT GASTRIC ACID SECRETION!!
o Suppression of prostaglandin production by NSAIDs = ↑HCl secretion

Question 11

Discuss the common sites and causes of peptic ulcers and what they’re called

Answer 11

• Duodenal Cap - first part of duodenum
• Stomach - juncture of antrum and body
• Distal Oesophagus - Barrett’s oesophagus
• Ileum - Meckel’s Diverticulum
• After Gastroenterostomy - connect stomach and jejunum

Question 12

How are peptic ulcers diagnosed?

Answer 12

• Endoscopy - camera into stomach
• Histological examination and staining of a Biopsy
• Test for H. Pylori - Stool antigen test, Urea breath test

Question 13

What are the 2 types of peptic ulcers? Where do they occur? What are they caused by? What is their healing outcome?

Answer 13

Acute Peptic ulcer:
• Occurs in areas of corrosive gastritis, and severe stress/shock (burn, trauma)
• Caused by ACUTE HYPOXIA of surface epithelium - e.g. gastric mucosa ischaemia
• Outcome - Haemorrhage, Complete healing with no scarring, Chronic peptic ulcer

Chronic Peptic ulcer:
• Occurs in Upper GIT - Asymptomatic in most people
• Caused by Hyperacidity, H. Pylori infection, Duodenal reflux, NSAIDs
• Outcome - Complete healing and replacement of tissue with some scarring

Question 14

What are the complications of a peptic ulcer?

Answer 14

• Haemorrhage (GI bleeding)
• Perforation (Peritonitis) and Penetration (liver and pancreas may be affected) - leakage of luminal contents into peritoneal cavity
• Narrowing of Pyloric canal - Pyloric and Oesophageal stricture
• Malignancy - especially in H. Pylori infection

Question 15

What are the 3 Anti-secretory agents used? Give an example

Answer 15

1. H2 Antagonists (Antihistamines) - e.g. Ranitidine
   • Inhibits histamine action at H2 receptors on Parietal cells
   • Reduce Gastric acid secretion → reduce Pepsin secretion
   • Can decrease acid secretion by 90%
   • Side effects - Diarrhoea, cramps, rashes, hypergastrinemia, gynaecomastia
2. Proton Pump Inhibitors (PPI) - e.g. Lansoprazole
   • Are the drugs of choice if hypersecretion occurs e.g. Zollinger-Ellison syndrome
   • Inactive at neutral PH and irreversibly inhibit H/K ATPase pumps
   • Decreases gastric acid secretion
   • Side effects - Diarrhoea, headache, rashes, dizziness, gynaecomastia
3. Prostaglandins - e.g. PGE1 analogue, called Misoprostol
   • Inhibition of Gastric acid secretion by acting on Parietal cells
   • Increases mucosal blood flow and Bicarbonate secretion