AssessmentsGastroesophageal reflux disease (GERD)
Gastroesophageal reflux disease (GERD)
USMLE® Step 1 style questions USMLE
USMLE® Step 2 style questions USMLE
A 60-year-old man comes to the emergency department because of sub-sternal chest pain for an hour. He has experienced this pain before, typically after heavy meals, during times of stress, and when he goes running in the park. 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. Medical history is non-contributory. ECG shows normal sinus rhythm. Which of the following is the most likely diagnosis?
Content Reviewers:Viviana Popa
Contributors:Will Wei, Evan Debevec-McKenney, Elizabeth Nixon-Shapiro, MSMI, CMI, Victoria Silvia Recalde
So gastroesophageal reflux disease, or GERD, is when stomach acid flows back into the esophagus.
The presence of acid in the esophagus can lead to Barrett’s esophagus, a serious complication of GERD where the normal mucosa of the esophagus is replaced by one that’s similar to that of the intestines.
Barrett’s esophagus poses a higher risk of developing esophageal adenocarcinoma.
Normally, the wall of the entire gastrointestinal tract is made of 4 layers: the inner mucosa, the submucosa, a muscular layer, and an outer layer called the adventitia.
The mucosa is further divided into three layers - an innermost epithelial layer, a middle layer called the lamina propria, and an outermost layer, in contact with the submucosa, called the muscularis mucosae, which is made up of smooth muscle that contracts and helps with the breakdown of food.
Now, the stomach mucosa is different from the esophageal mucosa.
Inside the stomach, the epithelial layer is made up of cylindrical cells, which dive into the lamina propria, forming pits.
These pits are the gastric glands, and there are many of them scattered throughout the stomach.
Distributed among the cylindrical gland cells, there’s different types of secretory cells.
First, there’s G cells, which are a type of neuroendocrine cells that secrete a hormone called gastrin in response to food entering the stomach.
Gastrin stimulates another type of cells, the parietal cells, to release hydrochloric acid.
And then, there’s chief cells, which secrete an enzyme called pepsinogen.
Hydrochloric acid and pepsinogen are useful for digestion, but they can be quite aggressive for the delicate mucosa.
Luckily though, the stomach also has some defense mechanism in place.
First, the gastric glands also have foveolar cells, also called surface mucus cells, because they are closer to the surface of the stomach, and they secrete mucus.
Mucus is mostly made up of water and glycoproteins, and also bicarbonate ions which are also secreted by foveolar cells.
This bicarbonate-rich mucus protects the gastric mucosa from our own gastric acid, so it won’t get digested along with food.
Lastly the gastric mucosa is highly vascularized, which helps deliver oxygen and bicarbonate and carry away acid that makes it through into the lamina propria.
The esophagus, on the other hand, is better adapted for the passage of food. So its mucosa is made up of stratified squamous epithelium, which is better equipped to resist abrasion from food going down.
The downside is that this kind of epithelium doesn’t have defense mechanisms, like the stomach - so it’s more susceptible to acid damage.
So to protect the esophageal mucosa, at the lower end of the esophagus there's the lower esophageal sphincter - or LES, which is a circular muscle that relaxes when we swallow, to allow the passage of food, and closes between meals to prevent acid reflux.
The lower esophageal sphincter has a resting pressure of 10 to 45 millimeters of mercury. When the pressure is lower than normal, which means the sphincter becomes looser, gastric acid reaches the esophagus and the pH of the esophagus drops from to around 4 - which is called acid reflux.
Some esophageal defense mechanisms against acid reflux are the primary and secondary peristaltic waves.
Some degree of acid reflux is normal, especially after meals, but it doesn’t last long, since secondary peristaltic waves, which are contractions of the esophageal muscular layer that happen a while after we’ve already swallowed, push the gastric acid back into the stomach.
Finally, saliva also helps neutralize the acidic gastric content.
Now, when the pressure of the lower esophageal gets lower for some reason, reflux persists for longer, becoming pathological.
Persistent acid reflux damages the esophageal mucosa, causing local inflammation, or esophagitis.
Esophagitis, in turn, causes edema and erosion of the mucosa, which leads to more complications.
First off, every time the epithelium and the underlying tissue is damaged, it’s replaced by a scar.
Since this is continuously happening, the scar becomes bigger and bigger, and together with the edema, they turn the wall thicker, and the lumen through which the food passes becomes smaller - which is called esophageal stenosis.
Also, when the epithelium is continuously damaged and replaced, the new epithelium of the lower esophagus is gradually replaced by a single layer of columnar cells, similar to intestinal cells, that are more adapted to withstand the reflux.
- "Robbins Basic Pathology" Elsevier (2017)
- "Harrison's Principles of Internal Medicine, Twentieth Edition (Vol.1 & Vol.2)" McGraw-Hill Education / Medical (2018)
- "Pathophysiology of Disease: An Introduction to Clinical Medicine 8E" McGraw-Hill Education / Medical (2018)
- "CURRENT Medical Diagnosis and Treatment 2020" McGraw-Hill Education / Medical (2019)
- "Objective Documentation of the Link between Gastroesophageal Reflux Disease and Obesity" American Journal of Gastroenterology (2007)
- "Guidelines for the Diagnosis and Management of Gastroesophageal Reflux Disease" American Journal of Gastroenterology (2013)
- "Overprescribing proton pump inhibitors" BMJ (2008)