The most common mechanisms to protect against reflux are the anti-reflux physical barrier, the esophageal clearance, and the esophageal mucosal resistance.
The anti-reflux barrier is made of the lower esophageal sphincter (LES), the angle of His, the crural diaphragm, and the phrenoesophageal ligament. On resting conditions, LES maintains a high-pressure zone that is 15-30 mmHg above intragastric pressures, which is about 3mmHg. This depends on individual variability. One of the most common mechanisms of GERD is the excess of transient relaxation of the LES (TRLES) which occurs in absence of pharyngeal swallow or oesophageal peristalsis and lasting approximately 10 to 45 seconds. This is a physiological process that occurs postprandially to help evacuating excess of gas, but it occurs too frequent in individuals with GERD and it is the most common mechanism. The second most common cause of GERD is the inadequately low tone of the LES due to disruption of the physical barrier (hiatal hernia) or the overcoming gastric pressure over a hypotensive LES (increasing gastric or intraabdominal pressure such as high gastric volume, obesity, gastroparesis or pregnancy.
Reduced mucosal clearance can happen in cases of ineffective primary peristalsis (weak or absent oesophageal contractions) or abnormal decreased secondary peristalsis that both should be helping anterograde clearance.
Regarding the oesophageal mucosal resistance, we know there are factors such as saliva that contain bicarbonate and can help buffering the acid content and growth factors, such as epidermal growth factor, which promote mucosal repair and defenses hence preventing mucosal injury. Also GERD is associated with dilated intercellular spaces and increase of permeability leading to a loss of physical barrier. Histologically can associate basal cell hyperplasia, elongation of the lamina propria papillae and inflammatory infiltrates, however this is likely an effect of acid damage rather than a cause. Pepsin is one of the enzymes than can damage the oesophageal lining, but it needs the acidity caused by hydrochloric acid when gastric content ascend up the oesophageal lumen to be active. The submucosal plexus contains sensitive neural fibres that can transmit the painful signalling to the CNS regardless of mucosal macroscopic inflammation. That is individual dependent and it is influence by many factors including individual visceral sensitivity, therefore there will be a big spectrum of symptoms with some patients having clear reflux mediated mucosal damage (erosions or ulcers) but no symptoms and inversely, painful or symptomatic non erosive reflux disease (NERD)
| LES | Crural diaphragm | Angle of His |
|---|---|---|
|
Myogenic smooth muscle fibres Predominantly innervated by inhibitory neurons located in the body of the esophagus. When peristalsis occurs , this send inhibitory signal that relaxes the LES for approximately 5-10 seconds |
Considered the “external sphincter” of the LES Functions to increase pressure at the distal esophagus.
|
Acute angle between the stomach and the esophagus. It is created by the collar sling fibres and the circular muscles around the gastroesophageal junction |
Regarding the oesophageal mucosal resistance, we know there are factors such as saliva that contain bicarbonate and can help buffering the acid content. Also growth factors, such as epidermal growth factor, which promote mucosal repair and defences hence preventing mucosal injury. Also GERD is associated with dilated intercellular spaces and increase of permeability leading to a loss of physical barrier. Histologically can associate basal cell hyperplasia, elongation of the lamina propria papillae and inflammatory infiltrates, however this is likely an effect of acid damage rather than a cause.
Pepsin is one of the enzymes than can damage the oesophageal lining, but it needs the acidity caused by hydrochloric acid when gastric content ascend up the oesophageal lumen to be active. The submucosal plexus (Meissner) contains sensitive neural fibres that can transmit the painful signalling to the CNS regardless of mucosal macroscopic inflammation. That is individual dependent and it is influence by many factors including individual visceral sensitivity, therefore there will be a big spectrum of symptoms with some patients having clear reflux mediated mucosal damage (erosions or ulcers) but no symptoms and inversely, painful or symptomatic non erosive reflux disease (NERD)
Other clinical pictures can be mistaken for reflux
- Supragastric belching ( air ingested or injected into the oesophagus does not reach the stomach before eructation, this can happen many times during the day and it is different from aerophagia (swallowing too much air that usually reaches the stomach)-
- Gastric belching (where air in the proximal stomach is vented during a transient LES relaxation)
- Rumiation: Subconsciously learnt postprandial behaviour, effortless regurgitation of most meals following consumption, due to the involuntary contraction of the muscles around the abdomen. In this syndrome there is no no retching, nausea, heartburn, or abdominal pain associated with the regurgitation as there is with typical vomiting, and the regurgitated food is undigested. It is though to be due to increased pressure of the abdominal muscles. Rumination is treated with behavioural therapy.
- Globus: Constant or intermittent sensation of a lump or a presence stuck in the throat. It is not painful and usually located between the sternal notch and thyroid cartilage. It is not associated with dysphagia odynophagia . It is NOT asscociated with GERD.
- Chronic cough and wheezing: The association of GERD with both entities is not as common as it is thought, and despite the frequent consultation from respiratory and ENT team, chronic cough may represent hyper-responsive behaviour, where reflux is one of several triggers for coughing bouts, such as abrupt changes in temperature or humidity, prolonged talking or voice use, strong odours or scents, food triggers and postnasal drips. This is proved in the low rates of response to treatment in patient who deny typical GERD symptoms. One easy way to prove this theory is initiating PPI to the patient and assess if lanryngeal/respiratory symptoms improve, or assess with PhMetry in cases with doubts.