Continuing Education Activity
Gastric acid production is necessary for the body to digest food and break down nutritional components into absorbable amino acids, carbohydrates, and fats. Most of the acid is produced when gastric pH stimulates the release of gastrointestinal using the release and activation of various digestive enzymes. The stomach is a relatively acidic environment with a pH of less than 4.0, which can drop to 2.0 with parietal cells. Parietal cells live in the fundus and the body of the stomach and secrete hydrogen ions. This activity explains when this condition should be considered on a differential diagnosis, articulates how to properly evaluate for this condition, and highlights the role of the interprofessional team in caring for patients with this condition.
Objectives:
Describe the etiology of stress-induced gastritis.
Review the pathophysiology of stress-induced gastritis.
Summarize the treatment options for stress-induced gastritis.
Outline the importance of enhancing care coordination among the interprofessional team to ensure proper evaluation and management of stress-induced gastritis.
Introduction
Gastric acid production is necessary for the body to digest food and break down nutritional components into absorbable amino acids, carbohydrates, and fats. Most of the acid is produced when gastric pH stimulates the release and activation of various digestive enzymes. The stomach is a relatively acidic environment with a pH of less than 4.0, which can drop to 2.0 with parietal cells. Parietal cells live in the fundus and the body of the stomach and secrete hydrogen ions. Three predominant substances stimulate hydrogen ion secretion.[1][2][3]
Neurotransmitter acetylcholine (ACH) stimulates parietal cells via the phospholipase pathway to secrete hydrogen. Phospholipase is stimulated on the cellular wall, cleaving PIP into IP3 and DAG, releasing calcium ions into the cytoplasm. These calcium ions bind calmodulin and stimulate protein kinase C (PKC). PKC leads to the phosphorylation and activation of the hydrogen/potassium ATPase (H/K ATPase), resulting in acid secretion. The source of ACH is from the vagus nerve (cranial nerve X).
Gastrin is a hormone known to stimulate hydrogen ion secretion via the same mechanism of ACH, resulting in the activation of the H/K ATPase. Gastrin is predominantly secreted via the G cells, located in the antrum of the stomach, which are stimulated by the presence of amino acids and ACH in the gastric lumen.
Histamine stimulates parietal cells to secrete hydrogen ions via the cAMP pathway via the activation of protein kinase A and activate the H/K ATPase. Histamine is predominantly secreted via the mast cells from the surrounding gastric tissues.
The dysregulation of the above-mentioned mechanisms can result in hemorrhagic or erosive gastropathy, also known as stress gastritis. The mucosal barrier is disrupted secondary to an acute illness. This article aims to discuss the etiology and methods of preventing and identifying stress gastritis.
Etiology
AlteredpH can disrupt homeostatic digestion, resulting in dysregulation of gastric pH.In the clinical setting,this dysregulation is typically due tophysiologicstress, leading to inflammation of the stomach, known as stress-induced gastritis.In the stressed state, elevate levels of ACH and histamineresult 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 decreasesand 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 careunit, nasogastric tube output may become bloody. A patient may even develop hematemesis.
Esophagogastroduodenoscopy (EGD) may showdiffuse 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 isa 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 isPPIadministration, and the second line is the use of histamine blockers.[3][6][7]
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 thePPI 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 secretioninhibitors in the form of PPIs and H2 blockersto 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 circ*mstances.
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
Consultations
Patients with stress-related gastritis are usually managed in intensive care units. Gastroenterology service should be consulted if there are any signs or symptoms related to ulcer development. Neurosurgery and general surgery teams should be consulted if stress gastritis arises in the setting of head injury or buns, respectively. Interprofessional teamwork improves mortality and morbidity outcomes in the setting of stress ulceration. Pharmacy services play a key role in determining the appropriate doses of medications, especially in patients with significant other comorbidities.
Deterrence and Patient Education
Stress gastritis is defined as sores in the digestive tract that can cause stomach upset and lead to bleeding. Symptoms include upper abdominal pain, nausea, vomiting, or blood in the stool. In stressful situations, there is excess acid in the system, and the protective layer of mucus on the lining is broken down, which makes it more susceptible to damage. Prophylactic treatment in intensive care units leads to the decreased recurrence of stress ulcers. Healthcare providers are the best source of information for concerns related to stress-related ulcer formation.
Pearls and Other Issues
Early use of PPIs and H2 blockers in patients can be beneficial to prevent stress gastritis.
PPIs work to inhibit hydrogen ion secretion by blocking the H/K ATPase of parietal cells.
Parietal cells are stimulated by acetylcholine, gastrin, and histamine to secrete hydrogen ions.
Acetylcholine and gastrin via phospholipase and PKC to stimulate hydrogen ion secretion.
Histamine works through cAMP and PKA to stimulate hydrogen ion secretion.
Themost common presenting symptom is bleeding (bloody nasogastric tube, melena).
Enhancing Healthcare Team Outcomes
Stress-induced gastritis is commonly encountered in clinical practice by the primary care provider, nurse practitioner, emergency department physician, pharmacist, and internist. The diagnosis is initially suspected based on the history and treated empirically with PPIs. If the symptoms resolve, the patient is urged to undertake stress-relieving measures, discontinue smoking, caffeinated beverages, alcohol, and NSAIDs.[8]
Unfortunately, most patients remain non-compliant with preventive methods and have a recurrence of symptoms regularly. Some of these patients may benefit from upper endoscopy to rule out an organic disorder. Long-term PPI therapy for more than 12 months is not recommended. Instead, one may use antihistamines.[9]
References
- 1.
Siddiqui AH, Farooq U, Siddiqui F. StatPearls [Internet]. StatPearls Publishing; Treasure Island (FL): Apr 16, 2023. Curling Ulcer. [PubMed: 29493972]
- 2.
Saavedra JM, Benicky J. Brain and peripheral angiotensin II play a major role in stress. Stress. 2007 Jun;10(2):185-93. [PubMed: 17514587]
- 3.
Tryba M, May B. Conservative treatment of stress ulcer bleeding: a new approach. Scand J Gastroenterol Suppl. 1992;191:16-24. [PubMed: 1411292]
- 4.
Auguste LJ, Lackner R, Ratner L, Stein TA, Bailey B. Prevention of stress-induced erosive gastritis by parenteral administration of arachidonic acid. JPEN J Parenter Enteral Nutr. 1990 Nov-Dec;14(6):615-7. [PubMed: 2125645]
- 5.
Dahshan A, Patel H, Delaney J, Wuerth A, Thomas R, Tolia V. Gastroesophageal reflux disease and dental erosion in children. J Pediatr. 2002 Apr;140(4):474-8. [PubMed: 12006966]
- 6.
Knodell RG, Garjian PL, Schreiber JB. Newer agents available for treatment of stress-related upper gastrointestinal tract mucosal damage. Am J Med. 1987 Dec 18;83(6A):36-40. [PubMed: 3321977]
- 7.
Peura DA, Johnson LF. Cimetidine for prevention and treatment of gastroduodenal mucosal lesions in patients in an intensive care unit. Ann Intern Med. 1985 Aug;103(2):173-7. [PubMed: 3874573]
- 8.
Laudanno OM. Cytoprotective effect of S-adenosylmethionine compared with that of misoprostol against ethanol-, aspirin-, and stress-induced gastric damage. Am J Med. 1987 Nov 20;83(5A):43-7. [PubMed: 3120585]
- 9.
MacDonald AS, Steele BJ, Bottomley MG. Treatment of stress-induced upper gastrointestinal/hemorrhage with metiamide. Lancet. 1976 Jan 10;1(7950):68-70. [PubMed: 54585]
Disclosure: Rishi Megha declares no relevant financial relationships with ineligible companies.
Disclosure: Umer Farooq declares no relevant financial relationships with ineligible companies.
Disclosure: Peter Lopez declares no relevant financial relationships with ineligible companies.
