bubble_chart Overview

Stress ulcer is an acute gastric mucosal lesion that occurs under severe stress reactions such as multiple trauma, severe systemic infection, large-area burns, shock, and multiple organ failure. It is one of the common causes of upper gastrointestinal bleeding. Stress ulcers have four main characteristics: ① They are acute lesions that occur under stress; ② They are multiple; ③ The lesions are scattered in the acid-secreting areas of the gastric body and fundus containing parietal cells, rarely involving the gastric antrum, which may occasionally be affected only when the condition progresses or worsens; ④ They are not accompanied by high gastric acid secretion.

bubble_chart Pathogenesis

Stress ulcers are caused by the digestion and destruction of gastric mucosal cells by gastric acid and pepsin. Gastric acid is a necessary condition for the formation of ulcers; without gastric acid, ulcers cannot occur. In normal individuals, the gastric mucosa is exposed to gastric acid and pepsin but is not digested because the gastric mucosa has its own protective mechanisms. The protective mechanisms of the gastric mucosa include the following three aspects:

(1) Gastric mucus barrier: The gastric mucosa secretes mucus. The mucus is thick and gelatinous, closely adhering to the surface of the gastric mucosa, separating the gastric lumen from the mucosal surface (luminal surface) of the gastric mucosal epithelial cells. Due to its unique molecular structure, the water within the mucus layer remains stationary and undisturbed, and the diffusion of H⁺ and pepsin within it is extremely slow. Therefore, the mucus barrier maintains a pH gradient between the epithelial cells and the gastric lumen.

(2) Gastric mucosal barrier: The luminal surface of the gastric mucosal epithelial cells is composed of a lipoprotein cell membrane. H⁺ in the gastric lumen cannot diffuse back into the cells against the concentration gradient through the cell membrane. The cell membrane forms an H⁺ barrier between the gastric lumen and the epithelial cells. The small amount of H⁺ that passes through the mucus barrier is also blocked by the epithelial cell membrane. The connections between gastric mucosal epithelial cells are very tight, preventing H⁺ from entering the cells.

(3) Neutralization by HCO₃^-: Gastric mucosal cells contain a large amount of carbonic anhydrase, which combines CO₂ and H₂O produced by oxidative metabolism in the cells and from the blood to form H₂CO₃, which then dissociates into HCO₃^- and H⁺. HCO₃^- enters the blood or interstitial fluid from the basal side (serosal side) of the cells or is transported into the gastric lumen from the mucosal side. In the mucus layer close to the mucosa, it neutralizes the small amount of H⁺ that penetrates the mucus layer. Even if a small amount of H⁺ enters the mucosal epithelial cells, it can be neutralized by HCO₃^- within the cells, maintaining the acid-base balance of the cells.

The gastric mucosa contains a large amount of prostaglandins, which stimulate the secretion of mucus and HCO₃^-, providing protection to the gastric mucosal cells. However, substances such as aspirin, indomethacin, phenylbutazone, bile salts, corticosteroids, and urea can damage the gastric mucosal barrier, leading to acute gastric mucosal lesions.

The maintenance of the normal function of the gastric mucosal barrier relies on the proper metabolism and continuous renewal of gastric mucosal epithelial cells. Metabolism requires oxygen and substrates. Under stress conditions such as shock, patients experience varying durations of hypotension and gastric microcirculation disorders, leading to gastric mucosal ischemia and hypoxia, which impair mitochondrial function, reduce ATP synthesis, and result in insufficient energy supply. Consequently, cellular dysfunction occurs, impairing the ability to produce and secrete mucus and HCO₃

^-. Both the mucus barrier and mucosal barrier functions are lost, allowing H⁺ to diffuse back into the cells, while the cells lack HCO₃^- to neutralize the incoming H⁺. This leads to cellular acidosis, lysosomal rupture, release of lysosomal enzymes, and ultimately cell autolysis, damage, and death. Additionally, due to energy deficiency, DNA synthesis is affected, preventing cell regeneration. Without replacement by regenerated cells, necrotic cells lead to ulcer formation. Gastric mucosal cells have minimal energy (glycogen) reserves and a relatively high metabolic rate, making them more susceptible to metabolic disruption from ischemia compared to other organs (e.g., liver, muscles). Among gastric mucosal epithelial cells, those in the gastric fundus have the highest metabolic rate, which explains why stress ulcers predominantly occur in the gastric fundus.

bubble_chart Pathological Changes

Within hours of a stressful event, fiberoptic gastroscopy reveals pale gastric mucosa with scattered red petechiae localized to the gastric fundus in nearly all patients. Microscopic examination shows mucosal edema, submucosal vascular congestion, and minimal inflammatory cell infiltration. Electron microscopy demonstrates disruption of epithelial cell membranes in multiple areas, with some regions showing complete epithelial cell sloughing, exposing the underlying lamina propria. Within 24 to 48 hours of the stressful event, the entire gastric body mucosa develops 1–2 mm diameter erosions. Microscopically, these erosions exhibit localized hemorrhage and coagulative necrosis. If the patient's condition improves with treatment, 90% of cases show signs of healing within 3 to 4 days, with complete healing typically occurring within 10 to 14 days. However, if the patient's condition continues to deteriorate, the erosions may coalesce and enlarge, leading to full-thickness mucosal sloughing and ulcer formation, extending into the muscularis mucosae and submucosa, exposing nutrient vessels. If these vessels erode and rupture, hemorrhage ensues.

bubble_chart Clinical Manifestations

The earliest manifestation is bleeding. Bleeding does not mark the onset of the disease, as the pathological changes have been present for some time prior. Initially, the mucosal lesions are shallow and few, not causing bleeding. Later, as the lesions increase in number and depth, bleeding may occur if preventive measures are not taken. Bleeding typically begins 5 to 10 days after the onset of stress. There is no pain accompanying the bleeding. The bleeding is intermittent, sometimes with intervals of several days between episodes, possibly due to the lesions appearing in batches, with old lesions healing while new ones form.

bubble_chart Diagnosis

Patients in the intensive care unit or those with shock, extensive burns, severe trauma or infection, organ failure (such as acute renal failure, adult respiratory distress syndrome, or liver failure) who develop upper gastrointestinal bleeding should first consider the possibility of stress-induced ulcers. Since the lesions are too shallow, barium meal X-ray examination has no diagnostic value. Fiberoptic gastroscopy can exclude other bleeding lesions and confirm the diagnosis. If the bleeding is heavy and unclear, selective angiography can be performed.

bubble_chart Treatment Measures

For massive bleeding caused by stress ulcers, due to the patient's poor overall condition and inability to tolerate surgery, coupled with the high postoperative rebleeding rate, medical treatment is generally attempted first, with surgical intervention considered only if medical treatment fails. The methods of medical treatment include:

(1) **Gastric tube suction** Continuous suction via a nasogastric tube can prevent gastric distension, remove gastric acid and accumulated blood, and monitor the bleeding status.

(2) **Gastric lavage with ice-cold saline or vasoconstrictors** Lavage with ice-cold saline (60ml per cycle) or instillation of vasoconstrictors (e.g., 8mg norepinephrine in 100ml glucose solution) can constrict mucosal blood vessels and achieve hemostasis.

(3) **Extragastrointestinal administration of vasoconstrictors** Instillation of 8mg norepinephrine in 250ml saline into the peritoneal cavity or selective arterial catheterization with an infusion of 0.2u/min of posterior pituitary vasopressin into the left gastric artery for 24 hours, gradually tapering the dose after bleeding stops.

(4) **Antacid therapy with intermittent gastric lavage** H₂ receptor antagonists (e.g., cimetidine) and prostaglandins may increase mucosal vascular congestion and bleeding, so some experts advise against their use in active bleeding cases.

(5) **Surgical treatment** Only about 10% of stress ulcer bleeding patients require surgery. Indications for surgery include: ① Massive bleeding from the outset, with persistent hypotension despite rapid blood transfusion; ② Continuous or intermittent minor bleeding requiring 2–3 units of blood transfusion within 24–48 hours. There is considerable debate regarding the choice of surgical approach. Initially, subtotal gastrectomy was performed, but postoperative rebleeding was common, indicating insufficient removal of bleeding mucosa or failure to prevent new bleeding sites in the remaining mucosa. While total gastrectomy has excellent hemostatic effects, stress ulcer patients are often in poor general condition, leading to high surgical mortality and numerous postoperative complications. Current approaches typically involve acid-reducing procedures and/or partial mucosal resection, as well as gastric devascularization. The former includes subtotal gastrectomy, vagotomy, and vagotomy with partial gastrectomy. Vagotomy not only reduces gastric acid secretion but also opens arteriovenous shunts in the stomach, decreasing mucosal blood flow. Some studies suggest that vagotomy has similar hemostatic efficacy to subtotal gastrectomy but with lower rebleeding and mortality rates, while vagotomy combined with partial gastrectomy yields better hemostasis and lower rebleeding rates than either method alone. Gastric devascularization involves ligating all gastric vessels (including the left and right gastric arteries and the left and right gastroepiploic arteries) except the short gastric arteries. Some reports indicate low rebleeding rates postoperatively, without gastric necrosis or complications associated with partial gastrectomy. Some advocate Roux-en-Y reconstruction after partial gastrectomy to prevent bile reflux and mucosal damage. For patients with postoperative rebleeding, early reoperation is recommended, preferably with near-total or total gastrectomy—procedures with reliable hemostatic effects—as these patients are unlikely to tolerate a second episode of postoperative bleeding or a third hemostatic surgery.

bubble_chart Prevention

Patients in stressful conditions are highly likely to develop stress ulcers. Therefore, such patients should be promptly treated by replenishing blood volume, correcting circulatory disorders, improving tissue perfusion, ensuring ventilation, administering oxygen, and using antibiotics to prevent infection. Although gastric acid secretion may not necessarily be excessive in patients with stress ulcers, gastric acid is a necessary condition for the development of stress ulcers. Thus, for patients in severe stress conditions, it is best to insert a gastric tube for continuous suction of gastric fluid—firstly to maintain an acid-deficient stomach and secondly to prevent gastric wall ischemia from worsening due to gastric distension. However, the gastric mucosa is fragile and prone to bleeding, so the suction force should not be too strong. Simultaneously, intravenous H₂ receptor antagonists (cimetidine) should be administered to inhibit gastric acid secretion, and antacids (magnesium milk or aluminum hydroxide) should be intermittently introduced through the gastric tube for gastric lavage to neutralize gastric acid. If conditions permit, 30ml of antacid can be instilled into the stomach via the gastric tube every hour, followed by clamping the tube for 45 minutes. The gastric fluid is then aspirated, and after 15 minutes of suction, the pH of the gastric contents is measured. If the pH is <5, 60ml is instilled in the second hour to maintain the pH of the gastric contents >5. Some do not advocate the use of H₂ receptor antagonists because when parietal cells produce gastric acid, each secretion of H⁺ is accompanied by the production of HCO₃^- (alkaline tide) secreted into the gastric lumen. H₂ receptor antagonists inhibit gastric acid secretion while also affecting the production of HCO₃^-, unlike antacids, which neutralize gastric acid without affecting HCO₃^- secretion.

bubble_chart Differentiation

Stress ulcers differ from other gastric mucosal lesions or ulcers:

(1) Acute mucosal lesions caused by alcohol, hormones, and non-hormonal anti-inflammatory agents (such as aspirin, indomethacin, etc.) are not accompanied by severe stress conditions like infection or trauma. The lesions are multiple superficial erosions, occurring in similar locations as stress ulcers but limited to the mucosa without invading the muscle layer, and heal without scarring. They generally do not cause massive bleeding, and any bleeding stops spontaneously without requiring surgical treatment.

(2) Curling ulcers caused by burns are also acute ulcers, but they occur during the convalescence stage of burns, whereas stress ulcers caused by burns appear 3–5 days after the burn. Curling ulcers are single, located in the duodenum, deeper, and often penetrate the intestinal wall, leading to perforation.

(3) Cushing ulcers caused by brain trauma, brain tumors, or intracranial neurosurgery occur in the esophagus, stomach, or duodenum and can penetrate the gastrointestinal wall. There is excessive secretion of gastric acid and pepsin (due to overstimulation of the vagus nerve), and elevated serum gastrin levels. In contrast, stress ulcers do not involve excessive secretion of gastric acid or pepsin.

Stress ulcers may not present clinical symptoms unless they cause massive bleeding, or even if symptoms exist, they may be masked by the symptoms of the stress condition and go undiagnosed. Additionally, because stress ulcers are relatively superficial, they often cannot be detected by barium meal contrast studies. As a result, they are frequently discovered only after massive bleeding through surgical exploration or postmortem autopsy, leading to many missed diagnoses. Previously reported incidence rates were not high. Although the clinical incidence has increased since the advent of fiber endoscopy, since not all patients under stress conditions undergo routine endoscopic examinations, the statistical incidence may still be much lower than the actual numbers.

Patients who develop stress ulcers due to burns generally have burn areas exceeding 35%. For burns covering less than 50% of the body, the incidence of stress ulcers is only 2% if not complicated by sepsis, but rises to 19% if sepsis occurs. Severe infections following trauma or surgery increase the likelihood of stress ulcers. Combined thoracoabdominal injuries are more likely to cause stress ulcers than isolated chest, soft tissue, or limb injuries. Chronic gastroduodenal ulcers or shock caused by bleeding from esophageal varices in cirrhosis also frequently lead to stress ulcers.