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A 52-year-old man comes to the emergency department because of severe abdominal pain. He has felt this pain for months, but it has become intolerable over the last 7 hours. He has a history of gastroesophageal reflux disease (GERD), hypertension, and diabetes. He says that eating exacerbates the pain. He thought he was just having some indigestion and would take some antacids for relief. However, since the pain worsened, he is now having trouble moving. His temperature is 39.1°C (102.5°F), pulse is 115/min, and blood pressure is 135/75 mm Hg. He appears to be in severe distress, secondary to pain, and refuses to straighten his legs because it hurts too much. He has diffuse guarding and rebound tenderness. An upright chest radiograph shows free air under the right diaphragm. Which of the following is the most likely cause of the patient’s symptoms?
Content Reviewers:Rishi Desai, MD, MPH
Peptic refers to the stomach, and an ulcer is a sore or break in a membrane, so peptic ulcer disease describes having one or more sores in the stomach - called gastric ulcers - or duodenum - called duodenal ulcers- which are actually more common.
Normally, the inner wall of the entire gastrointestinal tract is lined with mucosa, which has three cell layers.
The innermost layer is the epithelial layer and it absorbs and secretes mucus and digestive enzymes.
The middle layer is the lamina propria and it contains blood and lymph vessels.
Then there’s the outermost layer which is the muscularis mucosa, and it’s a layer of smooth muscle that contracts and helps break down food.
In the stomach, there are four regions - the cardia, the fundus, the body, and the antrum.
So the epithelial layer in different parts of the stomach contains different proportions of gastric glands which secrete various substances.
Having said that, the cardia contains mostly foveolar cells that secrete mucus which is a mix of water and glycoproteins.
The fundus and the body have mostly parietal cells that secrete hydrochloric acid and chief cells that secrete pepsinogen, an enzyme that digests protein.
Finally, the antrum has mostly G cells that secrete gastrin in response to food entering the stomach. These G cells are also found in the duodenum and the pancreas, which is an accessory organ of the gastrointestinal tract.
Gastrin stimulates the parietal cells to secrete hydrochloric acid, and more broadly stimulates the growth of glands throughout the stomach.
In addition, the duodenum contains Brunner glands which secrete mucus rich in bicarbonate ions.
In fact, with all of the digestive enzymes and hydrochloric acid floating around, the stomach and duodenal mucosa would get digested if not for the mucus coating the walls and bicarbonate ions secreted by the duodenum which neutralizes the acid.
In addition, the blood flowing to the stomach and duodenum brings in even more bicarbonate which helps neutralize the hydrochloric acid.
Finally, the stomach and duodenum secrete small signalling molecules called prostaglandins.
Prostaglandins stimulate mucus and bicarbonate secretion, vasodilate the nearby blood vessels allowing more blood to flow to the area, promote new epithelial cell growth, and also inhibit acid secretion.
The main cause of gastric and duodenal ulcers is infection with H. pylori bacteria, especially in low-income countries and settings.
H. pylori are gram-negative bacteria that colonize the gastric mucosa and release adhesins that help them adhere to gastric foveolar cells as well as proteases that cause damage to mucosal cells.
The majority of individuals with H. pylori don’t develop any problems, but sometimes it causes a patchy pattern of damage that starts in the antrum, and then spreads to the rest of the stomach and eventually into the duodenum. Over time the damage erodes deeper and deeper into the mucosa, eventually causing ulcers.
NSAIDs inhibit the enzyme cyclooxygenase which is involved in the synthesis of inflammatory prostaglandins.
Reducing the level of prostaglandins over a prolonged period of time, however, leaves the gastric mucosa susceptible to damage, and over time ulcers can begin to develop.
A rare cause of peptic ulcer disease is Zollinger Ellison syndrome, which is due to a tumor called a gastrinoma.
A gastrinoma is a neuroendocrine tumor that is typically located in the duodenal wall or pancreas, and secretes abnormal amounts of gastrin.
Excess gastrin stimulates parietal cells to release excess hydrochloric acid, overwhelming normal defense mechanisms and allowing ulcers to develop in the first portion of the duodenum or even in the distal duodenum or jejunum.
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