Zollinger-Ellison syndrome

Definitions & Key takeaways

Zollinger-Ellison syndrome is a rare endocrine disorder characterized by a triad of one or more gastrinomas, increased gastric acid secretion, and peptic ulcers. The main symptom is epigastric pain from peptic ulcers, but also includes steatorrhea, weight loss, gastrointestinal bleeding, and diarrhea due to incomplete digestion and absorption. Zollinger-Ellison syndrome can be treated with acid-lowering medications and surgery to remove solitary tumors. Treatment involves reducing the production of stomach acid with medications, removing the tumor through surgery.

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Introduction0:00–0:30

Zollinger-Ellison syndrome, named after Dr. Zollinger and Dr.
Ellison - the two surgeons who first described it, is a rare endocrine disorder where there’s actually three interrelated pathologies.
First, there’s a gastrinoma, which is a gastrin-secreting tumor. Second, the gastrinoma leads to increased gastric acid secretion from parietal cells.
Third, the excess gastric acid causes peptic ulcers. Normally, the inner wall of the entire gastrointestinal tract is lined with mucosa, which consists of three cell layers.

Physiology0:30–3:24

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.
The outermost layer of the mucosa is the muscularis mucosa, and it is a layer of smooth muscle that contracts and helps with the breakdown of food.
In the stomach, there are four regions - the cardia, the fundus, the body, and the pyloric antrum. There’s also a pyloric sphincter, or valve, at the end of the stomach which closes while eating, keeping food inside for the stomach to digest.
The epithelial layer in different parts of the stomach contains different proportions of gastric glands which secrete a variety of substances.
Having said that, the cardia contains mostly foveolar cells that secrete mucus which is mostly made up 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 also stimulates the growth of glands in the epithelial layer.
In addition, the duodenum contains Brunner glands which secrete mucus rich in bicarbonate ions into the lumen. 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.
Since the stomach walls are constantly exposed to the acid, they have a thicker mucus layer when compared to the duodenum which is only momentarily exposed to the acid.
In addition, the blood flowing to the stomach and duodenum brings in even more bicarbonate which helps neutralize the hydrochloric acid.
Finally, small signalling molecules called prostaglandins get secreted in the stomach and duodenum and they stimulate mucus and bicarbonate secretion, vasodilate the nearby blood vessels allowing more blood to flow to the area, promoting new epithelial cell growth, and also inhibit acid secretion.
All the neutralizing mechanisms help in making the lumen of the small intestine basic. The basic environment is needed to activate the pancreatic digestive enzymes, like pancreatic lipase which breaks down fat.

Pathology3:24–5:28

In Zollinger-Ellison syndrome, G cells in the pancreas or duodenum develop a mutation which makes them divide uncontrollably and develop into gastrinomas.
These can be benign tumors which means that they don’t invade nearby tissues, or malignant tumors meaning that they do invade surrounding tissues and even spread through the lymph to distant ones.
In either scenario, the gastrinomas secrete large amounts of gastrin, which results in excess hydrochloric acid secretion.
That ends up overwhelming the protective bicarbonate and erodes the mucosa, resulting in peptic ulcers. The thin mucus layer of the duodenum is unable to protect it from the hydrochloric acid, so ulcers usually form in the duodenum rather than in the stomach.
Deep ulcers cause perforations, which means they erode all the way through the walls of the stomach or duodenum, allowing undigested food and gastric secretions to get into the peritoneal space - which is usually sterile.
Very deep ulcers can also erode into blood vessels running along the walls of the stomach or duodenum, and cause bleeding.
Also, increased hydrochloric acid makes food entering the duodenum really acidic, inactivating the pancreatic digestive enzymes.
Increased gastrin also stimulates so much growth of glands in the epithelial layer, that there’s thickening of the mucosal layer.
Gastrinomas can arise sporadically or they can be a part of an inherited syndrome. Sporadic gastrinomas are more common and usually occur as solitary tumors.
On the other hand, inherited syndromes that cause gastrinomas, like multiple endocrine neoplasia, or MEN, type I, are less common and usually cause multiple tumors.
Multiple endocrine neoplasia type I is an autosomal dominant disorder where a mutation in a tumor suppressor gene leads to adenomas or malignant tumors in the parathyroid gland, pituitary gland, and pancreas.

Symptoms5:28–6:10

Most of the symptoms of Zollinger Ellison syndrome are due to the peptic ulcers. This includes epigastric pain, which is an aching or burning in the upper abdomen, as well as bloating, belching, and vomiting.
Gastric ulcer pain typically increases while eating, because the food can irritate the ulcer and there’s more hydrochloric acid produced while eating.
In contrast, duodenal ulcer pain typically decreases while eating, because the closed pyloric sphincter doesn’t allow hydrochloric acid into the duodenum.
Another symptom is diarrhea due to incomplete digestion and absorption of food, and in some cases steatorrhea, which is when there’s undigested fat in the feces.

Diagnosis6:10–6:32

The diagnosis of Zollinger Ellison syndrome usually begins with the detection of peptic ulcers during endoscopy, and is confirmed by detecting high levels of gastrin in the blood, especially if they’re still elevated after giving secretin, which normally inhibits gastrin release.
An abdominal ultrasound can be done to detect tumors. Treatment for Zollinger Ellison syndrome includes medications which lower the gastric acid secretion and surgery may be done to remove solitary tumors.

Treatment6:32–6:43

All right, as a quick recap, Zollinger Ellison syndrome is a rare endocrine disorder characterized by a triad of one or more gastrinomas, increased gastric acid secretion, and peptic ulcers.

Review6:43–7:11

The main symptoms is epigastric pain from peptic ulcers, but also includes steatorrhea and diarrhea may also develop due to incomplete digestion and absorption.
Zollinger Ellison syndrome can be treated with acid-lowering medications and surgery to remove solitary tumors.