Stress-Induced Gastritis


Article Author:
Rishi Megha


Article Editor:
Peter Lopez


Editors In Chief:
Silvio de Melo Jr.
Vittorio Giuliano
Truptesh Kothari


Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Frank Smeeks
Kristina Soman-Faulkner
Trevor Nezwek
Radia Jamil
Patrick Le
Sobhan Daneshfar
Anoosh Zafar Gondal
Saad Nazir
William Gossman
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Hassam Zulfiqar
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John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Mark Pellegrini
James Hughes
Beata Beatty
Nazia Sadiq
Hajira Basit
Phillip Hynes
Tehmina Warsi


Updated:
4/9/2019 7:17:34 PM

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 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, and this can drop to 2.0 with the presence of parietal cells. Parietal cells live in the fundus and the body of the stomach and secrete hydrogen ions. Hydrogen ion secretion is stimulated by three predominant substances.[1][2][3]

  1. Neurotransmitter acetylcholine (ACH) stimulates parietal cells via the phospholipase pathway to secrete hydrogen. Phospholipase is stimulated on the cellular wall, which then cleaves 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).
  2. 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.
  3. 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. The aim of this article is to discuss the etiology, and methods of preventing and identifying stress 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, which can lead 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 patient 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 as well as 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 declines we found to be in gastritis and peptic ulcer disease population. Their decrease was 55% and 30% respectively and likely attributed the institution and early use of proton pump inhibitors (PPI) or histamine blockers. [5]

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. 

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 a 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.

A patient may have a review of systems positive for coffee ground emesis or melena. Abdominal pain is not always present.

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. 

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]

PPIs, the "azole" drugs 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.

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. 

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 with via phospholipase and PKC to stimulate hydrogen ion secretion
  • Histamine works through cAMP and PKA to stimulate hydrogen ion secretion
  • The most 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 the 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]


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Stress-Induced Gastritis - References

References

Siddiqui AH,Siddiqui F, Curling Ulcer (Stress-induced Gastric) 2019 Jan;     [PubMed]
Saavedra JM,Benicky J, Brain and peripheral angiotensin II play a major role in stress. Stress (Amsterdam, Netherlands). 2007 Jun;     [PubMed]
Tryba M,May B, Conservative treatment of stress ulcer bleeding: a new approach. Scandinavian journal of gastroenterology. Supplement. 1992;     [PubMed]
Auguste LJ,Lackner R,Ratner L,Stein TA,Bailey B, Prevention of stress-induced erosive gastritis by parenteral administration of arachidonic acid. JPEN. Journal of parenteral and enteral nutrition. 1990 Nov-Dec;     [PubMed]
Dahshan A,Patel H,Delaney J,Wuerth A,Thomas R,Tolia V, Gastroesophageal reflux disease and dental erosion in children. The Journal of pediatrics. 2002 Apr;     [PubMed]
Knodell RG,Garjian PL,Schreiber JB, Newer agents available for treatment of stress-related upper gastrointestinal tract mucosal damage. The American journal of medicine. 1987 Dec 18;     [PubMed]
Peura DA,Johnson LF, Cimetidine for prevention and treatment of gastroduodenal mucosal lesions in patients in an intensive care unit. Annals of internal medicine. 1985 Aug;     [PubMed]
Laudanno OM, Cytoprotective effect of S-adenosylmethionine compared with that of misoprostol against ethanol-, aspirin-, and stress-induced gastric damage. The American journal of medicine. 1987 Nov 20;     [PubMed]
MacDonald AS,Steele BJ,Bottomley MG, Treatment of stress-induced upper gastrointestinal/hemorrhage with metiamide. Lancet (London, England). 1976 Jan 10;     [PubMed]

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