Gastro- refers to the stomach, esophageal stands for esophagus, and reflux means “to
flow back”.
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.
This is called Barrett’s esophagus - or Barrett’s metaplasia, and the cylindrical
epithelium has a greater risk of degenerating into a particular type of esophageal cancer,
called adenocarcinoma.
Another complication is when the reflux goes all the way back up to the pharynx, and then
into the larynx, in which case it can cause laryngitis or even asthma.
Risk factors for developing GERD are factors that weaken the lower esophageal sphincter
- like obesity, a fat-rich diet, caffeine, alcohol, and smoking.
There’s also medications like antihistamines, calcium channel blockers, antidepressants,
benzodiazepines, and glucocorticoids.
Medical conditions that increase the risk for GERD include hiatal hernia, scleroderma,
and Zollinger-Ellison syndrome.
In hiatal hernia, the stomach and lower part of the esophagus slide up through the esophageal
hiatus, which is an orifice in the diaphragm, and this decreases the pressure of the lower
esophageal sphincter.
In scleroderma, the muscle of the lower esophageal sphincter is replaced by connective tissue,
so it can’t contract properly.
In Zollinger-Ellison syndrome, a tumor called gastrinoma secretes large amount of gastrin,
that stimulates hydrochloric acid secretion in excess, and makes reflux even worse.
Ok, now the most common symptom of chronic gastroesophageal reflux disease is pyrosis,
also called heartburn, which is a burning pain in the chest, just behind behind the
breastbone.
Another common symptom is regurgitation, where undigested food and a bit of gastric acid
go back up into the mouth, and can cause acidic taste, or even damage of the enamel layer
of teeth.
With stenosis, there may be dysphagia, which is a fancy way to say difficulty swallowing.
And if reflux goes into the respiratory tract, GERD might also present with chronic cough
or hoarseness.
All these symptoms, especially heartburn and regurgitation, worsen when lying down.
Most commonly, GERD is diagnosed based on the clinical symptoms, and a therapeutic challenge
is done.
This means proton pump inhibitors, which are medications that inhibit acid secretion, are
given, and with GERD, symptoms improve.
However, the most accurate study to diagnose GERD is a 24-hour pH monitoring in lower esophagus;
where a thin tube with an electrode attached is placed inside the esophagus in order to
detect how long the acid reflux stays in there.
X-rays with barium contrast of the upper GI tract can be useful to identify complications,
like ulcers or esophageal stenosis..
Also, an endoscopy - which is when a tube with a camera at the end is placed into the
esophagus - and a biopsy, are essential to diagnose Barrett’s esophagus and to evaluate
the risk of cancer.
If the biopsy shows normal intestinal cells under the microscope, and there are signs
of inflammation, this is called non-dysplastic Barrett's, and the risk of developing esophageal
cancer is very low.
However, if the cells look abnormal, that's called dysplasia, and there’s a higher risk
of developing adenocarcinoma.
Lifestyle changes, antacids, and proton pump inhibitors are the first line treatment for
GERD.
Lifestyle changes include losing weight in overweight individuals and avoiding spicy,
fatty foods, chocolate, coffee, and alcohol.
Additionally, keeping the head elevated during sleep and not lying down immediately after
a meal are recommended.
Medications include antacids, which neutralise acidity of gastric secretions, and proton
pump inhibitors, as well as H2 receptor blockers, which decrease hydrochloric acid production
in the first place.
Other choices include prokinetic medications, which increase the tone of the lower esophageal
sphincter, and the GABA agonist baclofen, which inhibits transient LES relaxations,
especially after meals.
Surgery can be done when pharmacological treatment is not effective, and the most common procedure
is Nissen fundoplication, where the gastric fundus is wrapped around the lower esophageal
sphincter in order to make it tighter.
Finally, for Barrett’s metaplasia, there’s different treatments depending on the stage.
Non-dysplastic can be followed up with an endoscopy every three years.
In case of dysplasia there’s options like surgery, endoscopic resection, or laser treatments.
All right, as a quick recap... gastroesophageal reflux disease, or GERD, is a condition where
a decreased tone of the lower esophageal sphincter causes an excessive amount of stomach acid
to flow back into the esophagus.
This causes the epithelium of the lower esophagus to constantly renew, and when it’s replaced
by columnar epithelium, that’s called Barrett’s esophagus.
Risk factors for GERD including obesity, a fat-rich diet, caffeine, alcohol, and smoking.
Symptoms include heartburn, regurgitation, or dysphagia.
Mucosal damage can cause inflammation, or esophagitis, which can lead to complications
like stenosis and Barrett’s esophagus.
Diagnosis can be done based on clinical symptoms, but the gold standard is 24 hour PH-monitoring.
An endoscopy and biopsy can be done to diagnose Barrett’s esophagus.
Treatment includes lifestyle changes, and medications like antacids and proton pump
inhibitors.
For Barrett’s esophagus, treatment depends on the stage of
the metaplasia.