Oesophagus
A muscular tube with two jobs — push food down, keep acid out — and almost every oesophageal disease is a failure of the pump, the valve, the lining, or the veins underneath it.
What it normally does
Swallowing sets off a single wave of squeeze that travels top to bottom (peristalsis). The striated muscle of the upper oesophagus is driven directly by sequential vagal firing; in the smooth-muscle lower two-thirds, nerves in the wall (myenteric plexus) time it: excitatory neurons contract the segment behind the bolus, while inhibitory neurons using nitric oxide and VIP relax the segment ahead and open the valve at the bottom. The wave, not gravity, does the work — which is why you can swallow lying down or upside down.
Kill those inhibitory neurons and the wave disappears and the bottom valve never opens — achalasia.
The bottom of the tube is held shut by a ring of smooth muscle that is contracted at rest (lower oesophageal sphincter). Two mechanical extras help it: the crura of the diaphragm pinch around the same spot, and the tube meets the stomach at a sharp angle (angle of His) that acts as a flap valve.
When the sphincter relaxes at the wrong times, or a hiatus hernia slides it up away from the diaphragm, stomach contents come back up — reflux.
The lining is tough squamous epithelium built for friction, not acid. It has no thick adherent mucus-bicarbonate gel like the stomach's — submucosal glands secrete some mucus and bicarbonate, but far less protection. Its main defences against acid are gravity, the clearing peristaltic wave, and swallowed saliva, which is bicarbonate-rich and alkaline.
Repeated acid exposure injures the lining and eventually makes it change into a different tissue — oesophagitis, then Barrett.
Veins from the lowest few centimetres drain two ways at once: upward into the azygos vein (systemic circulation) and downward into the left gastric vein (portal circulation). This is one of the few places the two venous systems join (portosystemic anastomosis), and the connecting veins sit in the submucosa under very thin tissue.
If pressure in the portal system rises, blood is forced backwards through these veins and they balloon under a thin lining — varices.
What goes wrong
- Gastro-oesophageal reflux disease (GORD)← from “The bottom of the tube is held shut by a ring …”
The sphincter relaxes when it should not. Everyone has brief transient relaxations after a meal; in GORD there are more of them, and each one lets acidic stomach contents into a tube with no acid defences. A hiatus hernia makes it worse by sliding the sphincter up through the diaphragm, so the muscular ring and the crural pinch no longer sit at the same level and the flap-valve angle is lost. Anything that raises intra-abdominal pressure — central obesity, pregnancy — pushes harder against a valve that is already leaking.
About one in ten to one in seven Australian adults gets weekly heartburn. Diagnosis is clinical; scope for alarm features — dysphagia, weight loss, vomiting, anaemia or GI bleeding — or when symptoms do not settle on acid suppression.
You would find: Burning behind the sternum after meals, worse lying flat or bending forward, sometimes regurgitation of sour fluid into the mouth, or a sudden flood of watery saliva (waterbrash — reflex salivation, not refluxed acid). Symptoms respond to acid suppression. Can present instead as chronic cough, hoarseness or non-cardiac chest pain — exclude cardiac chest pain first.
- Barrett oesophagus← from “The lining is tough squamous epithelium built …”
Squamous lining that is repeatedly acid-burned is replaced by columnar lining with goblet cells (intestinal metaplasia) — a tissue that tolerates acid better. The trade-off is that this new tissue is genetically unstable. Some of it becomes dysplastic, and a small fraction of that becomes oesophageal adenocarcinoma.
Roughly 0.1–0.5% per year progress to adenocarcinoma (cohort estimates vary) — low for the individual, but oesophageal adenocarcinoma is rising in Australia and is usually found late. Management is surveillance endoscopy plus acid suppression, with endoscopic resection or ablation once dysplasia appears.
You would find: Found at endoscopy, not at the bedside: salmon-pink tongues of mucosa extending above the gastro-oesophageal junction, confirmed on biopsy showing intestinal metaplasia. Typically a man over fifty with years of reflux and central obesity. Reflux symptoms may settle even as the disease progresses — quieter symptoms are not less disease.
The inhibitory nitric-oxide-releasing neurons of the myenteric plexus are progressively destroyed, probably by an immune process. Excitatory cholinergic input is left unopposed, so the sphincter stays tonically shut and never relaxes on swallowing, and the body of the oesophagus loses its coordinated wave. Food stacks up above a closed valve and the oesophagus dilates over years.
Rare (about 1 per 100,000 per year) but examined constantly. A tumour at the junction mimics it exactly (pseudoachalasia) — short history, older patient, marked weight loss — so everyone gets an endoscopy before being labelled achalasia.
You would find: Dysphagia to solids AND liquids from the beginning, over months to years. Regurgitation of undigested food with no acid taste, often onto the pillow at night, sometimes causing aspiration. Patients arch the neck or drink water to force food down. Barium swallow shows a dilated body tapering to a 'bird beak'; manometry is the diagnostic test — absent peristalsis with incomplete sphincter relaxation.
- Oesophageal varices← from “Veins from the lowest few centimetres drain tw…”
Cirrhosis makes the liver stiff, so portal venous pressure rises. Blood is forced backwards along the left gastric vein and up into the submucosal veins of the lower oesophagus, which dilate. By Laplace, wall tension climbs with diameter and pressure while the mucosa over them stays paper-thin, and eventually one ruptures into the lumen.
In Australia the usual causes are alcohol-related liver disease, chronic hepatitis B and C, and metabolic-associated fatty liver disease. Chronic liver disease falls disproportionately on Aboriginal and Torres Strait Islander communities — higher chronic hepatitis B prevalence, higher alcohol-related liver disease, and substantially higher death rates — so variceal bleeding is a real presentation, and hepatitis B screening and treatment is prevention of this exact event.
You would find: Large-volume vomiting of fresh blood, or black tarry stool, in a patient with signs of chronic liver disease — jaundice, spider naevi, palmar erythema, ascites, splenomegaly. No warning pain. Can exsanguinate: resuscitate first, endoscopy for band ligation within hours.
What we give, and how it works
Open a drug to see what it binds, what that does to the cell, and what you then see in the patient.
- Binds
- The H+/K+ ATPase (the proton pump) on the secreting surface of the gastric parietal cell — the final common step of acid secretion, whatever stimulated it.
- Which does
- A prodrug that only turns into its active form in strong acid, so it concentrates exactly where acid is being made — the parietal cell canaliculus — and binds the pump covalently. That pump is out of action for good; secretion returns only as the cell builds new pumps. This is why the effect outlasts the drug, which is cleared from blood in a couple of hours.
- So you see
- Acid output falls sharply — enough to hold intragastric pH above about 4 for most of the day, though not to abolish acid altogether. Reflux still happens — the valve is untouched — but what comes up is far less corrosive, so heartburn settles in days and erosive oesophagitis heals over about eight weeks.
- And the same mechanism causes
- Stomach acid is a sterilising barrier for everything you swallow. Blunt the acid and organisms that would have been killed are more likely to survive into the bowel — the basis for the observed association between long-term PPI use and Clostridioides difficile and other enteric infections.
- Handling
- The prodrug needs pumps that are actively working, so it does most of its job taken 30–60 minutes before a meal. Swallowed at random after eating, it underperforms — a common reason a patient is labelled 'PPI-resistant'.
Catches people out: PPIs treat the acid, not the valve and not the metaplasia. In Barrett oesophagus they control symptoms but the management is surveillance endoscopy looking for dysplasia. An H2 receptor antagonist (famotidine) blocks only the histamine arm of acid secretion, so it is weaker, and tolerance (tachyphylaxis) develops within days to weeks, so it is not a substitute for a PPI in erosive disease. New dysphagia, weight loss, vomiting or anaemia means endoscopy, not a bigger dose.
- Binds
- L-type voltage-gated calcium channels in the sphincter's smooth muscle membrane.
- Which does
- Blocking the channel cuts calcium entry, so less calcium binds calmodulin, so myosin light chain kinase is less active and fewer cross-bridges form. Resting tone falls.
- So you see
- Sphincter pressure drops and food drains through under gravity. Dysphagia eases somewhat — the relief is modest, inconsistent, and tends to fade with continued use.
- And the same mechanism causes
- The same L-type channel holds tone in arteriolar smooth muscle everywhere else. Relax those and arterioles dilate: throbbing headache, facial flushing, dizziness on standing, and ankle oedema as raised capillary hydrostatic pressure pushes fluid into the tissue.
- Handling
- Nitrates do the same job from the other direction — they supply the nitric oxide the lost inhibitory neurons can no longer release, raising cGMP in the sphincter. Same vasodilator headache. Both are taken shortly before meals.
Catches people out: Drugs are the weakest option in achalasia. Definitive treatment is mechanical: pneumatic dilatation, Heller myotomy, or peroral endoscopic myotomy (POEM). Botulinum toxin injected into the sphincter cleaves SNAP-25 so acetylcholine vesicles cannot fuse, dropping tone — but the effect typically wears off within 6–12 months, and repeated injections scar the plane a surgeon later needs.
- Binds
- Beta-1 adrenoceptors on cardiac myocytes and beta-2 adrenoceptors on splanchnic arteriolar smooth muscle — the point is that the drug is non-selective; a cardioselective beta blocker does not work here.
- Which does
- Beta-1 blockade lowers heart rate and cardiac output, so less blood reaches the gut. Beta-2 blockade removes the vasodilator arm in mesenteric arterioles, leaving alpha-mediated constriction unopposed. Both reduce inflow into the portal system.
- So you see
- Portal pressure falls, variceal wall tension falls, and the chance of rupture drops. Carvedilol adds alpha-1 blockade, which also lowers resistance inside the cirrhotic liver, and is now the preferred agent in most guidelines.
- And the same mechanism causes
- Beta-2 receptors also relax bronchial smooth muscle. Block them and the airway narrows — a genuine hazard in asthma, and the reason the non-selectivity that makes the drug work is also what makes it dangerous.
- Handling
- The same beta-1 blockade blunts the tachycardic response to blood loss, so a bleeding patient on propranolol may look deceptively stable. Judge them on blood pressure, perfusion and haemoglobin, not pulse.
Catches people out: The drug buys risk reduction, not cure. Endoscopic band ligation removes the varix; TIPS decompresses the portal system; treating the cause — alcohol, hepatitis B or C, metabolic liver disease — is the only thing that changes the trajectory.
- Binds
- V1 vasopressin receptors on splanchnic arteriolar smooth muscle.
- Which does
- V1 is a Gq-coupled receptor: phospholipase C makes IP3, IP3 releases intracellular calcium, the arteriole constricts. Less arterial blood enters the gut, so less blood enters the portal vein.
- So you see
- Portal pressure falls within minutes and bleeding slows or stops, buying time for endoscopic band ligation.
- And the same mechanism causes
- V1 receptors sit on vessels everywhere and the drug cannot pick. Constrict them all and any territory with a thin margin turns ischaemic — angina and chest pain, dusky cold fingers and toes, patchy skin ischaemia. Ask about ischaemic heart disease and peripheral vascular disease before giving it.
- Handling
- Terlipressin has some V2 activity as well, which drives free water reabsorption in the collecting duct and can drop the sodium sharply — watch for confusion and check the sodium.
Catches people out: Octreotide is the alternative, but it is a somatostatin analogue, not a vasopressin analogue — it acts on somatostatin receptors and lowers splanchnic flow indirectly, largely by suppressing vasodilator gut peptides such as glucagon. Do not file it under V1. Neither drug is definitive: band ligation controls the bleed, and prophylactic antibiotics (ceftriaxone) on admission improve survival in variceal bleeding as much as anything else you do.
Dysphagia to solids AND liquids from the outset points to a motility problem, achalasia being the classic one. Solids first, then liquids, progressing over a few months, in an older patient losing weight, is cancer until endoscopy proves otherwise. Same word — dysphagia — opposite urgency.
Now test whether it stuck
Reading this through is not the same as being able to reconstruct it. Every question in the bank is free, with a full debrief on each option.