Page created on February 4, 2019. Last updated on May 15, 2020 at 20:45
Peptic ulcer disease is a condition where a person has one or more peptic ulcers in the stomach or duodenum. It’s associated with H. pylori infection, NSAID abuse, stress, Cushing syndrome and Zollinger-Ellison syndrome (rare).
The pain related to gastric ulcers is worsened after food intake while the pain related to duodenal ulcers is improved after food intake.
High cell turnover, bicarbonate secretion and a protective mucin layer are all important defense mechanisms against peptic ulcers. They depend on prostaglandins to work properly.
The gastric mucosa produces 1.5 – 2 litres of gastric juice every day. HCl and intrinsic factor are produced by the parietal cells, pepsinogen from the chief cells. The gastric juice also contains K+, Na+, Cl– and mucus.
The pepsin in the gastric juice helps digest the food, but it is not strictly necessary for the digestion as pancreatic trypsin can take over the role of pepsin. This means that low or absent gastric juice doesn’t directly impair digestion. The gastric juice is not useless however as it has important antibacterial properties.
During fasting is the gastric juice secretion 30-40 mL/hour and it contains 1 – 4 mEq of acid. This amount of acid is the basal acid output (BAO). The maximal acid output (MAO) is 5 – 10 times higher than the BAO and is evoked by a drug called pentagastrin.
The secreted HCl keeps the pH of the gastric content around 1.5 – 4.0 even after being mixed with food. The low pH is essential for the conversion of pepsinogen to pepsin. Acidic pH inhibits gastric secretion by negative feedback. HCl can be stimulated by histamine paracrinally, gastrin endocrinally or the neurotransmitter acetylcholine.
Hypersecretion and hyposecretion are conditions where the amount of gastric juice is higher or lower than normal, respectively. When there is no production of gastric juice is the condition called achylia gastrica. In hyperchlorhydria is the HCl content higher than normal, in hypochlorhydria is it lower, and in achlorhydria is HCl absent.
When the gastric mucosa atrophies will the HCl secretion be impaired first, then the pepsinogen secretion, and lastly the intrinsic factor.
A peptic ulcer is a tissue defect that reaches at least into the submucosa, but frequently even deeper. More superficial damage is called an erosion. Peptic ulcer disease is a relatively common disease with severe consequences. They frequently occur in the stomach but can also occur in the duodenum as well.
The stomach mucosa is protected from the stomach acid and pepsin by a multitude of factors:
- It has high turnover (the cells replicate quickly)
- A layer of mucin protects the mucosa
- It secretes bicarbonate which increases the pH in the vicinity of the mucosa
- Good blood flow
- Normal motility
When the balance between the aggressive factors (acid and pepsin) and the defensive factors is disturbed will an ulcer develop.
Good blood flow is essential as it “washes out” any acid that diffuses into the interstitium quickly. It also provides a steady supply of bicarbonate. Decreased perfusion is often seen in elderly, which contributes to the formation of “stress-ulcers” in that population.
The high cell turnover depends on the good perfusion. Prostaglandins increase the mucin production, perfusion, enhance bicarbonate secretion and inhibit acid secretion.
Restitution refers to the intact cells’ ability to spread to and cover an injured area to protect it from further injury. This depends on a good circulation and an intact basement membrane, so it is not possible in deeper injuries.
The following are risk factors for developing peptic ulcers:
- NSAIDs – these drugs inhibit COX, the enzyme that produces prostaglandins.
- Ethanol – causes vascular injury, increases HCl secretion and is cytotoxic in high concentrations
- Smoking – increases HCl secretion, decreases mucosal perfusion
- Corticosteroids – if combined with NSAIDs
- Coffee, tea, cola – increases HCl secretion
- Shock, trauma, burns, stress – decrease mucosal perfusion
- Helicobacter pylori
H. pylori is a bacterium that is famous for its ability to cause peptic ulcer. It produces the enzyme urease, which breaks down urea into NH3, which neutralizes the acid around it. It uses its flagella to dig into the mucus layer, where it’s protected from the stomach acid. It produces toxins that are cytotoxic to the mucosal cells.