Pathogenesis and the role of gastrinoma
Zollinger-Ellison syndrome develops due to the appearance of a gastrinoma—a hormonally active tumor most frequently localized in the pancreas. This tumor autonomously and uncontrollably secretes the hormone gastrin into the blood. The resulting hypergastrinemia powerfully stimulates the parietal cells of the gastric body. As a result, the most pronounced hydrochloric acid hypersecretion among all possible causes develops.
The excess acid critically shifts the balance on the so-called «Shay balance»—a pathological imbalance arises between aggressive factors (HCl, pepsin) and mucosal defense factors (mucus, bicarbonates, prostaglandins, adequate blood flow, and epithelial regeneration). The high acidity of gastric juice leads to constant pain, dyspepsia, and the formation of peptic ulcers. Unlike typical peptic ulcer disease, ulcer defects in gastrinoma have a progressive course and frequently recur.
Diagnostics and analysis of gastric secretion
To confirm the diagnosis, it is necessary to prove the presence of pathological hypersecretion and identify the tumor itself. Gastric contents are obtained using a thin tube and two key parameters are evaluated:
- Basal Acid Output (BAO): normally 0–12 mmol/h (average 2–3 mmol/h). In Zollinger-Ellison syndrome, this value is elevated multiple times.
- Maximal Acid Output (MAO): reflects the total functional mass of parietal cells after stimulation with pentagastrin or histamine.
A crucial differential diagnostic criterion for gastrinoma is the BAO/MAO ratio, which in this pathology approaches unity. This means the stomach is already working at its maximum capacity in the basal state.
For final verification of the diagnosis, the following are used:
- Radioimmunoassay — allows the detection of abnormally high blood gastrin levels.
- Abdominal ultrasound or CT — used for instrumental localization of the tumor in the pancreas.
Morphology and complications of chronic ulcer
The morphological manifestation of the disease is a persistent defect of the mucous membrane and submucosa, with the muscular layer forming its base. Ulcer defects have typical macroscopic features: a round or oval shape, as well as dense (callous) edges. Meanwhile, the edge facing the esophagus is usually undermined and overhanging, whereas the edge on the pyloric side appears sloping, resembling a terrace. A mandatory component of the pathogenesis is chronic inflammation of the mucous membrane.
The progressive course of the syndrome is associated with a high risk of ulcer complications:
- Hemorrhage — occurs from eroded blood vessels.
- Perforation — formation of a transmural hole.
- Penetration — a variant of perforation in which the base of the ulcer becomes the wall of a tightly adjoining adjacent organ.
- Gastric outlet stenosis — when decompensated, leads to chlorhydropenic uremia.
- Malignant transformation — malignant conversion of a callous ulcer (a precancerous condition requiring biopsy).
Differential diagnosis of hypersecretion
Pronounced hydrochloric acid hypersecretion and ulcerative lesions of the gastrointestinal tract occur not only in gastrinoma. During the diagnostic process, Zollinger-Ellison syndrome should be differentiated from other hypersecretory conditions detected during probing:
- Metabolic: hypercalcemia of any origin (calcium directly stimulates gastrin release and HCl production).
- Neurological: brain injuries leading to increased vagus nerve (n. vagus) tone, which enhances vagal stimulation of parietal cells.
- Surgical: conditions after small bowel resection, due to which intestinal factors that normally inhibit secretion are lost.
- Pancreatogenic: chronic pancreatitis or obstruction of the pancreatic ducts.
To remember the asymmetry of the edges of a chronic ulcer, use the «E–P» rule: Esophageal edge is Undermined, and Pyloric is Sloping.
Class and exam questions
Why does the BAO/MAO ratio tend to unity in gastrinoma?
The tumor continuously secretes huge doses of gastrin into the bloodstream, which is why the gastric parietal cells work at their maximum capacity even under basal conditions, without additional stimulation.
Which tests finally confirm the diagnosis?
It is necessary to laboratory-confirm high blood gastrin levels (using radioimmunoassay) and visualize the pancreatic tumor itself using ultrasound or CT methods.
What is the difference between ulcer perforation and penetration?
Perforation is the rupture of an organ wall into a free cavity. Penetration represents a specific variant of perforation in which the defect is covered, and the base of the ulcer becomes the wall of an adjacent organ.
What else to study on this topic
- Pathogenesis of peptic ulcer disease: the «Shay balance» and the role of defense factors
- Etiopathogenetic classification of ulcers (drug-induced, symptomatic, idiopathic)
- The role of Helicobacter pylori infection in the formation of chronic ulcer defects
- Differential diagnosis of pyloric channel peptic ulcer and ulcerated gastric cancer
- Chlorhydropenic uremia as a consequence of decompensated gastric outlet stenosis
- Evaluation of duodenal probing results: calculation of hydrochloric acid debit-hour
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