Stress-Induced Gastritis

Etiology

Altered pH can disrupt homeostatic digestion, resulting in dysregulation of gastric pH. In the clinical setting, this dysregulation is typically due to physiologic stress, leading to inflammation of the stomach, known as stress-induced gastritis. In the stressed state, elevate levels of ACH and histamine result in increased acid production, thus inducing gastritis.[4]

Patients are typically found in the surgical unit of the hospital or the medical or surgical intensive care unit. These critically ill patients have typically undergone physiologic stress related to severe trauma, severe burns, ventilator dependency, on intracranial trauma.

Physiologic stress leading to stress gastritis results in gastric erosions, known as curling ulcers. Erosions secondary to cranial etiology are named Cushing ulcers after the famous neurosurgeon Harvey Cushing. 

The first step in the development of stress-induced gastritis is decreased mucosa resistance from toxic radicals. The stress response of the body results in the decrease of gastric renewal, leading to atrophy of the gastric mucosa. Blood flow to the stomach decreases and makes the stomach more prone to acid-pepsin ulceration and hyperacid secretion.

Epidemiology

In 2002, Wuerth et al. reported the incidence of upper gastrointestinal hemorrhage to be approximately 81 cases per 100,000; this number decreased to 67 cases per 100,000 by 2012. The greatest decline was found to be in the gastritis and peptic ulcer disease population. Their decrease was 55% and 30% respectively and likely attributed to the institution and early use of proton pump inhibitors (PPI) or histamine blockers.[5] Estimates of the asymptomatic form of gastritis, in critically ill patients, who are not receiving prophylaxis are high (approximately >75 percent). Stress gastric ulcer with occult bleeding has an incidence rate of 15 to 50 percent, with overt bleeding is 1.5 to 8.5 percent, and of stress gastric ulceration with clinically significant bleeding is even low at 1 to 3 percent.

Pathophysiology

Increased acid secretion leads to the development of erosions that can lead to gastric hemorrhage. Although these bleeds may not be life-threatening initially, they may cause patient discomfort or melanotic stools in the early phase and severe hemorrhage 4 to 5 days later. 

Stress results in the release of angiotensin II, which decreases blood flow to the mucosa. This causes reactive oxygen species formation, which attacks DNA and results in 8-hydroxydeoxyguanosine (8-OHdG) formation. This results in an oxidative mutagenic byproduct and, subsequently, oxidative stress on the mucosa. On the other hand, naturally produced nitric oxide is believed to protect against stress gastritis because it promotes vasodilation. 

Initial symptoms may be persistent nausea associated with epigastric pain, but hemorrhage is typically the first symptom. For a patient in the intensive care unit, nasogastric tube output may become bloody. A patient may even develop hematemesis. 

Esophagogastroduodenoscopy (EGD) may show diffuse gastric inflammation and mild erosions in the stomach and duodenum. These ulcers tend to be shallow. Typically, acute gastric erosions in burn or severe trauma patients can be seen within 3 days of injury. 

The most common presenting symptom of stress-induced gastritis is a hemorrhage. Very rarely, approximately 10%, patients will develop perforation.

Histopathology

Gastritis is characterized by inflammation, mucosal edema, vascular dilation, smooth muscle proliferation in the lamina propria, and vascular congestion. The glands in the gastric mucosa may appear tortuous or take on a corkscrew appearance. There is neutrophilic infiltration and active granulation with mononuclear infiltration within mucosal layers. Fibrinoid necrosis may also be found. In chronic forms, lymphocytes, monocytes, and plasma cells infiltrate the mucosa and submucosa.

History and Physical

A patient presenting with stress-induced gastritis usually has undergone a recent stressful physiologic event, such as severe polytrauma from a significant motor vehicle collision or a fall resulting in multiple broken bones. Stress-induced gastritis also can be elicited by severe illness, like ventilator-dependent pneumonia or a massive myocardial infarction. Finally, patients may present with stress gastritis after major surgery. It is pertinent to mention that some forms of psychiatric stressors such as major, untreated depression can result in stress gastritis. 

The physical exam may demonstrate stable or unstable vitals, depending on the eliciting insult. If a patient has undergone major surgery, the vitals may be stable; however, the insult to the body may still be great. In a patient who experienced a massive myocardial infarction, one would expect more labile vitals. Lastly, a patient with polytrauma and hemodynamic instability would be expected to have very unstable vitals until resuscitated.The following signs and symptoms are present in typical cases.

• Coffee ground vomitus
• Hematemesis
• Melena
• Abdominal pain
• Nausea
• Orthostasis in severe cases

Evaluation

If a nasogastric tube is placed after flushing with normal saline, the return may be blood-tinged. An upper gastrointestinal bleed often can be ruled out after nasogastric tube placement, and the gastric lavage returns bilious content. A fecal occult blood test (FOBT) is also performed. Endoscopy is used to make a definitive diagnosis. Stress gastritis is seen as small superficial mucosal erosions or erythematous lesions in the gastric body and fundus. Testing for H. pylori infection like urease breath test or stool antigen test can also be undertaken.

Treatment / Management

The onset of improved critical care has decreased the incidence of stress-induced gastritis. The mainstay of treatment is PPI administration, and the second line is the use of histamine blockers.[3][6][7](A1)

PPIs, such as omeprazole, and lansoprazole, are irreversible inhibitors of the H/K ATPase. This results in decreased hydrogen ion secretion regardless of the levels of acetylcholine and gastrin as the drug directly inhibits the enzyme. Patients placed on PPIs will develop a paradoxical elevation in gastrin. Because of this, if the PPI is stopped, this patient will develop an acute increase in acid production. This is secondary to the loss of inhibition of the H/K ATPase, with an artificially elevated level of gastrin.

H2 blockers, such as famotidine, do not affect the H/K ATPase of parietal cells directly. These function to inhibit the histamine-mediated stimulation of parietal cells, thus resulting in decreased phosphorylation and activation of H/K ATPase via protein kinase A.

For this, it is imperative for early administration of acid secretion inhibitors in the form of PPIs and H2 blockers to critically ill patients to prevent stress-induced gastritis. Since the etiology of gastric stress comes from angiotensin, studies are being conducted on how to reduce the effects of angiotensin on the gastric mucosa.

Differential Diagnosis

The following should also be considered in the differential diagnosis:

• Peptic ulcer disease
• Nonsteroidal anti-inflammatory drug (NSAID)–induced gastritis
• Alcoholic gastropathy
• Gastroesophageal reflux disease (GERD)
• Gastric or esophageal cancer
• Gastroparesis
• pancreatic cancer
• Biliary pain
• Uremic gastropathy
• Dyspepsia

Pertinent Studies and Ongoing Trials

Proton pump inhibitors (PPIs) have always been considered superior to histamine receptor-2 (H2) blockers to prevent stress-related gastritis in critically ill patients at risk. Recent studies have raised the concern of increased mortality in patients who receive PPIs for stress-ulcer prophylaxis. Large trials directly comparing the agents for stress ulcer prophylaxis are lacking, and further studies are needed to determine whether PPIs are harmful. Data also suggest the potential role of angiotensin on gastritis, and studies are being conducted on how to reduce the effects of angiotensin on the gastric mucosa.

Staging

Histopathologic based classification is given below:

• Lesion Ia
  • Focal intramucosal hemorrhage with or without submucosal hemorrhages. Hemorrhages into lamina propria are also seen, with separation of gastric glands.
• Lesion Ib
  • Focal submucosal hemorrhages are seen, with mucosal edema. No cellular response or necrosis.
• Lesion Ic
  • Focal intramucosal ulcer with or without submucosal hemorrhages along with the destruction of glandular mucosa is present.
• Lesion II
  • White mucosal plaques with metaplasia of gastric pit epithelium and gland tortuosity are seen.

Prognosis

Prognosis is predominantly dependent on the severity of the eliciting event. However, if the patient is otherwise hemodynamically stable and prophylaxis with PPI or histamine blocker is disregarded, life-threatening intestinal hemorrhage may occur, followed by perforation, resultant septic shock, and possible death. If aggressive prophylactic measures for the appropriate patient population at risk of developing stress ulceration are employed, prognosis usually remains favorable in most circumstances.

Complications

Stress ulceration can be associated with the following complications.

• Bleeding
• Anemia
• Strictures
• Perforation
• Peritonitis
• Gastrocolic fistula due to ulcer perforation
• Gastric outlet obstruction due to strictures
• Hemorrhagic shock
• Increased length of ICU stay
• Death