Transcript for High Yield: Gastroesophageal reflux disease, gastritis, and peptic ulcers
High Yield: Gastroesophageal reflux disease, gastritis, and peptic ulcers
A 61-year-old man, named Shawn, comes to the emergency department because of substernal chest pain and heartburn.
He mentions that his symptoms worsen typically after coffee, heavy meals or during times of stress.
He also feels the pain at night when he is lying in bed and has previously been woken from sleep by discomfort.
He has not noticed any dyspnea, diaphoresis, or palpitations but is currently experiencing some nausea and a sour taste in his mouth.
Shawn also denies a history of previous cardiovascular conditions.
His ECG is normal.
Shawn has gastroesophageal reflux disease, or GERD.
GERD is a condition caused by a transient lower esophageal sphincter relaxation, which enables stomach contents and acid to re-enter esophagus and damage esophageal mucosa.
As a result, people with GERD present with symptoms such as retrosternal chest pain, heartburn, regurgitation, and dysphagia.
It’s important to note that GERD symptoms tend to worsen after eating, when lying down, or bending over.
Now, if stomach acid gets to the throat, it can cause laryngopharyngeal reflux, which has a different set of symptoms such as acidic taste in the mouth, sore throat, chronic cough, and hoarseness.
In the mouth, gastric acid can even damage tooth enamel.
GERD is commonly associated with conditions such as decreased esophageal motility, gastric outlet obstruction, and hiatal hernia.
Risk factors for GERD include lifestyle habits such as caffeine, alcohol, and smoking; use of some medications, such as antihistamines and calcium channel blockers; but also, obesity; pregnancy; and Zollinger-Ellison syndrome.
Now, a classic GERD presentation can be diagnosed based on clinical symptoms and history alone, but diagnostic methods such as endoscopy or x-ray with barium contrast can be useful in identifying GERD complications.
The treatment of gastroesophageal reflux disease is based on lifestyle changes, such as eating small servings and avoiding heavy food, coffee, alcohol, and smoking; and medical therapy, which includes the use of antacids, H2 receptor antagonists, and proton pump inhibitors.
Finally, surgical treatment can be an option in those individuals whose symptoms do not improve after medical therapy; or in individuals that have developed complications, such as esophageal strictures or Barrett's esophagus.
Now Barrett’s esophagus is a premalignant condition that develops when there’s chronic exposure of the lower part of the esophagus to stomach acid.
As mentioned, this is especially common in individuals with GERD.
The acid irritates the mucosa of the esophagus causing inflammation and subsequent necrosis.
Eventually, this results in metaplasia where the normal nonkeratinized stratified squamous epithelium of the lower esophagus is replaced with nonciliated columnar epithelium and goblet cells; a type of cell that’s better adapted to withstand the acidity.
Now you have to know that the intestinal metaplasia is a normal, adaptive response of the esophageal mucosa.
Like how you can get a tan when exposed to sunlight.
But if the irritation persists, metaplasia can progress to dysplasia and eventually esophageal adenocarcinoma.
Individuals with Barrett’s esophagus are often asymptomatic, but in some cases, they can present with symptoms typical of GERD, such as heartburn, regurgitation, and dysphagia.
Finally, Barrett's esophagus is diagnosed by esophagogastroduodenoscopy with biopsy; and it’s treated by endoscopic ablation or surgical resection.
Moving on to esophageal cancer.
The two main types of esophageal cancer are adenocarcinoma and squamous cell carcinoma.
Esophageal adenocarcinoma typically affects the lower third of the esophagus and it’s the most common type of esophageal cancer in the United States of America.
Risk factors for esophageal adenocarcinoma include obesity, smoking, achalasia, chronic GERD, and Barrett’s esophagus.
Moreover, individuals with Barrett’s esophagus have 30-40 times increased risk of developing esophageal adenocarcinoma.
On the other hand, esophageal squamous cell carcinoma typically affects the upper two-thirds of the esophagus and it’s the most common type of esophageal cancer worldwide.
Risk factors for esophageal squamous cell carcinoma include smoking, alcohol, hot liquids, caustic strictures, and achalasia.
Another risk factor is food containing N-nitroso, like betel nuts, which is chewed like tobacco in Asian countries.
Initially, individuals with esophageal cancer are asymptomatic; but as cancer obstructs the esophageal lumen it causes problems, such as dysphagia, initially for solids and then for liquids.
This can also lead to weight loss.
Esophageal cancer has an aggressive course because there’s no serosa in the esophageal wall to serve as a barrier between the esophagus and surrounding structures.
Furthermore, individuals with esophageal cancer have a poor prognosis because they usually present late, in advanced stages of esophageal cancer.
Diagnosis is made by esophagogastroduodenoscopy, which is an imaging study that allows direct visualization and biopsy of esophageal cancer.
Finally, treatment options for this condition include endoscopic mucosal resection or mucosal ablation, esophagectomy, and chemoradiation.
Okay, let’s move down to the stomach and look at gastritis, which is an inflammation of the gastric mucosa.
There are two types of gastritis, acute and chronic gastritis.
Remember that acute gastritis is characterized by neutrophil infiltration; whereas chronic gastritis is characterized by lymphocyte and plasma cell infiltration.
First, let’s start with acute gastritis, which is caused by an imbalance between mucosal defenses and the acidic environment of the stomach.
Acute gastritis starts with gastric erosions, which are mucosal lesions that are limited to the mucosal layer only.
Gastric erosions should not be confused with gastric ulcers because ulcers can penetrate into the submucosa and or deeper.
Now, gastric erosions can be caused by excessive drinking of alcohol or long-term use of NSAIDs.
NSAIDs work by blocking an enzyme called cyclooxygenase, thereby inhibiting the production of prostaglandin E2 that normally increase the production of gastric mucus and decrease the production of gastric acid.
In other words, decreased production of prostaglandins impairs mucosal defense, eventually causing gastric erosions.
Also, acute gastric mucosal lesions can be caused by extreme physiological stress, such as sepsis, shock, and trauma.
These lessons can range from superficial erosions to full-thickness ulcers, which are called stress ulcers.
Now, you shouldn’t confuse stress ulcers with Curling’s ulcers or Cushing’s ulcers!
On the other hand, Cushing’s ulcers are seen in individuals with brain injuries, when there’s an overstimulation of the vagus nerve, which results in an increased production of ACh and gastric acid.
Now, here’s an easy way to distinguish the two: think of curling iron for Curling’s ulcers and burns; and on the other hand, think of the brain and how it needs to be cushioned for Cushing’s ulcers.
Once the causative stressors are eliminated, stress ulcers spontaneously heal over the next few weeks.
Individuals with acute gastritis typically present with epigastric pain, nausea, and vomiting; but in rare cases, they can present with life-threatening upper gastrointestinal bleeding that leads to melena.
On the other hand, in chronic gastritis, chronic inflammation leads to gastric atrophy, which is further followed by metaplasia.
If the inflammation persists, metaplasia can progress to dysplasia and eventually gastric adenocarcinoma.
Now, there are two types of chronic gastritis: chronic autoimmune gastritis and Helicobacter pylori-associated gastritis.
Chronic autoimmune gastritis, also known as type A gastritis, affects the body and fundus of the stomach; and it represents an example of a type IV hypersensitivity.
In chronic autoimmune gastritis, there are autoantibodies against H+/K+ ATPase on parietal cells and intrinsic factor.
Autoantibodies against H+/K+ ATPase decrease gastric acid secretion, thereby causing hypochlorhydria, which is associated with impaired iron absorption and hyperplasia of gastrin cells or short G-cells.
As a result, there’s an increased secretion of gastrin, hypergastrinemia, which is a hormone that has a trophic effect on enterochromaffin-like cells, or ECL cells; therefore, these individuals are at risk for developing neuroendocrine tumors.
Autoantibodies against intrinsic factor lead to decreased absorption of vitamin B12, resulting in pernicious anemia.
Finally, in chronic autoimmune gastritis chief cells are also lost and this results in decreased levels of serum pepsinogen.
Diagnosis of chronic autoimmune gastritis includes endoscopic biopsy, but also detection of anti-parietal cell antibodies, anti-IF antibodies; and levels of serum gastrin and pepsinogen.
On the other hand, Helicobacter pylori-associated chronic gastritis, also known as type B gastritis, is the most common type of gastritis.
Usually, it affects the antrum but it can spread to the body of the stomach.
Moreover. when the gastritis is mostly confined to the antrum, gastric acid levels are normal or elevated.
Now, for your exam, it’s important to know that Helicobacter pylori inflammation decreases the number of somatostatin-secreting cells, also known as delta cells.
Delta cells produce hormone somatostatin, which inhibits gastrin.
In type B gastritis, decreased somatostatin leads to high levels of gastrin, so there’s increased hydrogen ion secretion by parietal cells.
As a result, pH of the gastric fluid decreases, and the risk for developing duodenal ulcers and duodenal gastric metaplasia increases.
On the other hand, in extensive Helicobacter pylori-associated chronic gastritis, when inflammation spreads to the body of the stomach, level of gastric acid is typically low; therefore, there’s an increased risk of developing neuroendocrine tumors just like in chronic autoimmune gastritis.
Also, people with Helicobacter pylori-associated chronic gastritis have an increased risk of developing gastric MALT lymphoma.
Individuals with chronic gastritis can be asymptomatic, but in some cases, they can present with epigastric pain, nausea, and vomiting.
Diagnosis of Helicobacter pylori-associated chronic gastritis includes endoscopic biopsy, but also detection of Helicobacter pylori using serology, stool antigen test, and urease breath test.
Generally, chronic gastritis treatment is aimed at the underlying cause.
It usually involves antacids or antibiotics, because eradication of Helicobacter pylori improves symptoms and decreases the risk of malignancy.
Next, we have Ménétrier disease which is also called giant hypertrophic gastritis.
This is a form of gastritis which features hyperplasia of gastric mucosa and subsequent hypertrophy of gastric folds, also known as gastric rugae.
Hypertrophic rugae look like brain gyri, giving the stomach mucosa brain-like appearance.
In Ménétrier disease, there’s an excess production of mucus, which is further followed by protein loss and finally parietal cell atrophy.
As a result, there’s also decreased acid production.
For your exam, it’s important to remember that Ménétrier disease is a precancerous condition.
These individuals typically present with weight loss, anorexia, vomiting, epigastric pain, and edema, due to protein loss. You can remember the clinical presentation by the acronym WAVEE.
Now let’s focus on Peptic ulcers which are chronic lesions in areas exposed to excess gastric acid and peptic juices.
Based on their location, there are two types of peptic ulcers: gastric ulcers, which are most commonly located in the antrum and gastroesophageal junction; and duodenal ulcers, which are typically found in the proximal part of the duodenum, called duodenal bulb.
In 70% of cases, gastric ulcers are caused by Helicobacter pylori infection, the same ones that cause chronic gastritis.
Helicobacter pylori is a gram-negative, non-invasive bacteria.
This bacteria is actually sensitive to the acidic environment of the stomach, but in the stomach, it attaches to gastric mucosa or hides deep in the mucus that overlies gastric mucosa which protects it.
- "Robbins Basic Pathology"Elsevier(2017)
- "Harrison's Principles of Internal Medicine, Twentieth Edition (Vol.1 & Vol.2)"McGraw-Hill Education / Medical(2018)
- "Gastroesophageal Reflux Disease"New England Journal of Medicine(2008)
- "Gastroesophageal Reflux Disease"New England Journal of Medicine(2008)
- "Barrett's oesophagus"The Lancet(2009)
- "Barrett's oesophagus and oesophageal adenocarcinoma: time for a new synthesis"Nature Reviews Cancer(2010)
- "Barrett's oesophagus: from metaplasia to dysplasia and cancer"Gut(2005)
- "Inflammation, atrophy, and gastric cancer"Journal of Clinical Investigation(2007)
- "Ménétrier disease and gastrointestinal stromal tumors: hyperproliferative disorders of the stomach"Journal of Clinical Investigation(2007)
- "MANAGEMENT OF PATIENTS WITH ZOLLINGER-ELLISON SYNDROME"Annual Review of Medicine(1995)
- "Guide to the Use of Proton Pump Inhibitors in Adult Patients"Drugs(2008)