Gastroesophageal Reflux Disease and Peptic Ulcer

10 Questions

What enzyme is responsible for the synthesis of HCl in the stomach?

H+, K+-ATPase (proton pump)

How do Proton Pump Inhibitors (PPIs) accumulate in the parietal cell acid secreting spaces?

As weak bases, they accumulate in acid compartments and are converted into reactive thiophilic sulfenamide.

What is the result of the reaction between thiophilic sulfenamide and H+,K+-ATPase enzyme?

Covalent bonds are formed, blocking both basal and stimulated acid formation.

What is the effect of Misoprostol (Cytotec) on gastric acid secretion?

It stimulates prostaglandin E1 receptors on parietal cells, reducing gastric acid secretion.

What is the therapeutic benefit of Misoprostol (Cytotec)?

It promotes mucosal protection and wound healing.

What is the mechanism of action of Sucralfate (Ulsanic) in ulcer treatment?

It coats the base of an ulcer, protecting it from pepsin and allowing healing to take place.

What is the effect of Bismuth subcitrate (Ulcerone) on the ulcer?

It protects the ulcer from gastric acid and pepsin.

What is a common unwanted effect of Misoprostol (Cytotec) therapy?

Abdominal pains and diarrhoea (which are self-limiting).

What is the contraindication for the use of Misoprostol (Cytotec)?

Pregnancy.

What is the unwanted effect of Sucralfate (Ulsanic) therapy?

Constipation.

Study Notes

Gastroesophageal Reflux Disease (GORD)

GORD results from an imbalance between defensive factors protecting the oesophagus and aggressive factors from the stomach content
Defensive factors: antireflux barriers (LES, crural diaphragm, costal diaphragm, and the angle of His)
Aggressive factors: gastric acidity, volume, and gastric/duodenal content

Anatomy of the Oesophagus and Lower Gastroesophageal Sphincter (LES)

The oesophagus is a flat muscular tube that starts at the pharynx and ends at the stomach
At the level of the diaphragm, it is surrounded by collagen and elastic fibres
The vagus nerve supplies only parasympathetic innervation to the oesophagus, but below the neck, it carries a mixture of sympathetic and parasympathetic nerve fibres

Substances that Affect LES Pressure

Substances that affect LES pressure include spicy foods, peppermint, chocolate, tomatoes, onions, and alcohol
Pregnancy, smoking, and late snacks/sleeping immediately after eating heavy meals can also affect LES pressure

Treatment of GORD

Alginic or sodium alginate suspension (Gaviscon) floats on gastric content to treat GORD
Antacids (e.g., Mucaine, Magnesium trisilicate, and Aluminium hydroxide) and H2 blockers (e.g., Cimetidine and Ranitidine) can also be used to treat GORD
Non-drug management of GORD includes self-directed learning and lifestyle changes

Acid Peptic Disorders

Peptic ulcer disease (PUD) affects millions of people worldwide and has several possible causes, including NSAID use, smoking, alcohol, stress, and diet
Clinical manifestations of PUD include abdominal pain, burning pain localized to the epigastrium, and ulcer complications such as bleeding, perforation, and pyloric stenosis

Acid Peptic Disorders - Acid Secretion

Basal acid secretion follows a circadian rhythm, with low secretion in the morning and high secretion at night
Cholinergic and histaminergic stimulation are the main determinants of HCl secretion
Food ingestion is the principal physiological stimulant of HCl secretion

Acid Peptic Disorders - Mucosal Defence and Repair

Prostaglandins, nitric oxide, mucous and bicarbonate (HCO3-), mucosal blood flow, and stabilisation of mucosal mast cells and lysosomes play a role in mucosal defence and repair
Somatostatin plays an inhibitory role in acid secretion

Treatment of Peptic Ulcers

Proton Pump Inhibitors (PPIs) block the activity of H+, K+-ATPase enzyme in parietal cells, thus reducing acid secretion
Other drugs used to treat peptic ulcers include Misoprostol, Sucralfate, and Bismuth subcitrate, which promote mucosal protection and healing