The stomach is a muscular J-shaped sac sitting in the upper left abdomen, holding about 1-1.5 liters comfortably and up to 4 liters when distended. It runs at a pH of 1 to 2 — roughly the acidity of battery acid — and uses that environment plus enzymatic digestion plus mechanical churning to turn food into a semi-liquid slurry called chyme before sending it to the small intestine.
At a glance
What it does
Three things in parallel. It denatures protein using hydrochloric acid, which unfolds protein structure so pepsin (activated from pepsinogen by acid) can start breaking peptide bonds. It kills most incoming bacteria, viruses, and parasites through sheer acidity — a major but under-appreciated immune function. And it churns food mechanically to produce chyme of the right consistency to pass through the pylorus into the duodenum.
The stomach also produces intrinsic factor, which binds vitamin B12 so it can be absorbed in the distal ileum. Without intrinsic factor, B12 deficiency is inevitable. It produces ghrelin when empty, driving hunger. And it contains a surprisingly large fraction of the body's mast cells and immune tissue.
Gastric emptying is regulated by the contents of the duodenum — fats, acid, and osmolality all trigger feedback that slows emptying. This is part of why high-fat meals sit heavy, and part of why GLP-1 agonists cause early satiety and nausea.
How it works
The wall has five regions (cardia, fundus, body, antrum, pylorus) and several specialized cell types. Parietal cells secrete hydrochloric acid using the H+/K+ ATPase — the proton pump that proton pump inhibitors block. Chief cells secrete pepsinogen, which becomes pepsin in the acidic environment. G cells in the antrum secrete gastrin, which stimulates parietal cells to produce more acid. ECL cells secrete histamine, which also stimulates parietal cells (hence the use of H2 blockers like famotidine).
Mucus-producing surface cells secrete a thick bicarbonate-rich layer that protects the gastric lining from its own acid. Prostaglandins maintain this protective barrier, which is why NSAIDs — by inhibiting prostaglandin synthesis — cause gastric ulcers as a side effect.
Motor function includes slow tonic contractions of the proximal stomach (which store food) and phasic peristaltic waves starting at the pacemaker in the mid-body and sweeping toward the pylorus (which mix and empty). The interstitial cells of Cajal generate the pacemaker rhythm. Vagal input modulates both acid secretion and motility.
When it goes wrong
Helicobacter pylori changed the story of the stomach. Before the 1980s, peptic ulcers were blamed on stress and spicy food. We now know H. pylori is the main cause of peptic ulcer disease and a major risk factor for gastric cancer and MALT lymphoma. Test-and-treat with triple or quadruple therapy (PPI plus two or three antibiotics) is standard.
Gastroesophageal reflux disease is the common complaint driving a huge prescription volume. Acid refluxes through an incompetent lower esophageal sphincter, irritating or damaging the esophageal lining. Chronic reflux predisposes to Barrett's esophagus and esophageal adenocarcinoma. Treatment: weight loss, avoiding triggers, elevating the head of bed, and PPIs when needed.
PPIs are overused. They are excellent for erosive esophagitis, bleeding ulcers, and H. pylori eradication. They are frequently prescribed indefinitely for vague dyspepsia that should have been investigated or tried off therapy. Long-term PPI use has been linked to increased risk of C. difficile infection, pneumonia, hip fracture, B12 deficiency, and hypomagnesemia — effects are modest at the population level but real and under-appreciated by patients on decades of PPI therapy.
Gastric cancer is declining in developed countries but remains a major cancer globally, especially in East Asia. Risk factors include H. pylori, smoking, high salt intake, processed meat, and certain hereditary syndromes. Early-stage disease is often silent, which is why screening endoscopy is standard in high-incidence countries.
Gastroparesis — delayed gastric emptying without obstruction — causes nausea, early satiety, bloating, and vomiting of undigested food. Diabetes is the most common cause, plus idiopathic, post-surgical, and medication-induced (notably GLP-1 agonists cause functional slowing).
Interactions
Intrinsic factor dependence means chronic atrophic gastritis, long-term PPI use, and bariatric surgery that removes or bypasses the stomach all require B12 monitoring and often supplementation. Iron absorption also requires acid — PPIs can contribute to iron deficiency anemia.
NSAIDs and aspirin are the main drug-induced gastric injury culprits. Co-prescription with a PPI reduces ulcer risk substantially. Stress ulcers in critically ill patients are real and are one of the legitimate indications for prophylactic acid suppression.
Alcohol irritates the gastric mucosa and contributes to reflux by reducing LES tone. Smoking worsens reflux and ulcer healing.
Honest take
If you have reflux that has been going on for years, you owe yourself an endoscopy and an H. pylori test, not another year of over-the-counter omeprazole. PPIs are one of the better drugs in modern medicine when used appropriately, and one of the most overprescribed when not. The "acid reflux means you have low stomach acid" claim popular in functional medicine is almost always wrong — real hypochlorhydria is rare outside atrophic gastritis and surgical resection, and betaine HCl supplementation is not a substitute for actual diagnostic workup. On the other side: if you are on chronic daily PPIs without a documented indication, talk to your physician about a taper.
Sources
- Chey et al., American Journal of Gastroenterology — ACG guideline on H. pylori.
- Katz et al., American Journal of Gastroenterology — ACG guideline on GERD.
- Freedberg et al., Gastroenterology — AGA best practice advice on long-term PPI use.