Adult physiology
Healthy vs. Unhealthy Digestion
The stomach and oesophagus are situated within the upper gastrointestinal (GI) tract. Between them, at the gastroesophageal junction, lies a smooth circular muscle layer called the lower oesophageal sphincter (LOS).(1)
The LOS prevents the retrograde flow of the stomach contents into the oesophagus, also known as gastro-oesophageal reflux.(2) Its function is particularly important after meals when the stomach is full.(3)
Physiological transient relaxations of the LOS can lead to reflux events.(2) These often occur post-prandially where the increased stomach size causes a relaxation reflex called gastric accommodation to prevent increased intragastric pressure during food intake.(2) In most individuals, these reflux events do not cause symptoms.(2,3)
However, some individuals experience reflux symptoms such as heartburn.(2,3) These patients may have:(4)
- weak baseline sphincter strength
- a low sphincteric response to increased intra-abdominal pressure
- mechanical impairment of the LOS
Acid secretion
Gastric acid in the stomach mixes with food as it is ingested and becomes neutralised.(5) This stimulates further gastric acid production and secretion.(5)
Several cells in the stomach are involved in this process:(6,7)
Cells | Function |
---|---|
Parietal cells |
Secrete hydrochloric acid (HCl) into the stomach through proton pumps |
Enterochromaffin-like cells |
Secrete histamine to stimulate HCl secretion |
Gastrin cells |
Secrete gastrin to stimulate HCl secretion |
Delta cells |
Secrete somatostatin to inhibit HCl secretion |
Mucous cells |
Secrete mucus to protect the stomach lining |
After meals, newly secreted gastric acid accumulates, causing an acid pocket to form.(5,8) Sitting above the stomach contents, this acid pocket can be detected within 15 minutes of eating at the gastro-oesophageal junction and can persist for up to 2 hours. (5,8) This coincides with reflux events that happen within 3 hours after food intake.(9)
The highly acidic nature (pH<2)(5) and the close proximity to the LOS makes the acid pocket a contributor to postprandial reflux.(8) During reflux events, the acid pocket rises and comes into contact with oesophageal tissue,(5) leading to reflux symptoms and potential tissue damage.(10)
Pepsin and Bile
Acid is not the only substance associated with heartburn. Other substances such as pepsin and bile, present in the refluxate, can also seep into the oesophagus.(11-13)
Contact of pepsin and bile alongside gastric acid, with the oesophagus mucosa can impair its integrity, contributing to the likelihood of symptomatic reflux.(14)
Therefore, treatments that target gastric acid alongside bile and pepsin, may be the most effective way to treat heartburn.(13)
Factors associated with reflux
Several risk factors are associated with symptoms of reflux in patients. These include:(15,16)
- ≥ 50 years of age
- Hiatus hernia
- Obesity
- Pregnancy
- Tobacco smoking
Medications
- Non-steroidal anti-inflammatory drugs
- Antibiotics (e.g. tetracyclines and clindamycin)
- Statins
- Angiotensin-converting enzyme inhibitors
- Bisphosphonates
- Clomipramine
- Quinidine
- Anticholinergics
- Tricyclic antidepressants
- Corticosteroids (oral and inhaled)
- β-agonists
- Nitroglycerines
- Aminophylline
- Benzodiazepines
- Warfarin
- Cyproterone
- Ethinyl oestradiol
- Calcium channel blockers
Consumption of triggering foods and drinks
- Carbonated drinks
- Alcohol
- Chocolate
- Onion
- Coffee
- Tomato-based products
- Citrus juices
- Peppermints
- High-fat foods
- Spicy foods
- Boeckxstaens GE. The lower oesophageal sphincter. Neurogastroenterol Motil 2005;17 Suppl 1:13–21
- Pauwels A, Altan E, Tack J. The gastric accommodation response to meal intake determines the occurrence of transient lower esophageal sphincter relaxations and reflux events in patients with gastro-esophageal reflux disease. Neurogastroenterol Motil 2014;26(4):581–88
- Kahrilas PJ. GERD pathogenesis, pathophysiology, and clinical manifestations. Cleve Clin J Med 2003;70 Suppl 5:S4–S19
- Boeckxstaens G, El-Serag HB, Smout AJPM, et al. Symptomatic reflux disease: the present, the past and the future. Gut 2014;63(7):1185–93
- Fletcher J, Wirz A, Young J, et al. Unbuffered highly acidic gastric juice exists at the gastroesophageal junction after a meal. Gastroenterology 2001;121(4):775–83
- Kopic C, Murek M, Geibel JP. Revisiting the parietal cell. Am J Physiol Cell Physiol 2010;298(1):C1–C10
- Liu Y, Vosmaer GDC, Tytgat GNJ, et al. Gastrin (G) cells and somatostatin (D) cells in patients with dyspeptic symptoms: Helicobacter pylori associated and non-associated gastritis. J Clin Pathol 2005;58(9):927–31
- Kahrilas PJ, McColl K, Fox M, et al. The acid pocket: a target for treatment in reflux disease? Am J Gastroenterol 2013;108(7):1058–64
- Shoeman MN, Tippet MD, Akkermans LM, et al. Mechanisms of Gastroesophageal Reflux in Ambulant Healthy Human Subjects. Gastroenterology 1995;108(1):83–91
- Orlando RC. The Integrity of the Esophageal Mucosa. Balance Between Offensive and Defensive Mechanisms. Best Pract Res Clin Gastroenterol 2010;24(6):873–82
- Johnston N, Dettmar PW, Bishwokarma B, et al. Activity/stability of human pepsin: implications for reflux attributed laryngeal disease. Laryngoscope 2007;117(6):1036–9
- Nehra D, Howell P, Williams CP, et al. Toxic bile acids in gastro-oesophageal reflux disease: influence of gastric acidity. Gut 1999;44(5):598–602
- Strugala V, Avis J, Jolliffe IG, et al. The role of an alginate suspension on pepsin and bile acids - key aggressors in the gastric refluxate. Does this have implications for the treatment of gastro-oesophageal reflux disease? J Pharm Pharmacol 2009;61(8):1021–8
- Farre R, Fornari F, Blondeau K, et al. Acid and weakly acidic solutions impair mucosal integrity of distal exposed and proximal non-exposed human oesophagus. Gut 2010;59(2):164–69
- Eusebi LH, Ratnakumaran R, Yuan Y, et al. Global prevalence of, and risk factors for, gastro-oesophageal reflux symptoms: a meta-analysis. Gut 2018;67(3):430–40
- MacFarlane B. Management of gastroesophageal reflux disease in adults: a pharmacist’s perspective. Integr Pharm Res Pract 2018;7:41–52