Gastrointestinal system

The mouth wets, breaks up and packages food, then hands it over in a one-second reflex that has to shut the nose, shut the larynx and open the top of the oesophagus in the right order. Saliva keeps the mouth alive and the teeth intact; the swallow keeps food out of the lungs. When either fails, the damage is fast — teeth rot in months, lungs get infected in days.

What it does

Three paired major glands, plus several hundred minor glands scattered through the lips, cheeks and palate, make 0.5 to 1.5 litres of saliva a day. At rest most of the volume comes from the submandibular glands (a mixed, sero-mucous, slightly stringy secretion); when you eat or smell food the parotids take over with a thin watery fluid rich in amylase. The minor glands add little volume but much of the mucin. Production is unusual in being driven almost entirely by the parasympathetic nervous system — acetylcholine on M3 muscarinic receptors on the acinar cells (via the chorda tympani from the facial nerve, relaying in the submandibular ganglion, to the submandibular and sublingual glands; and via the lesser petrosal nerve from the glossopharyngeal nerve, relaying in the otic ganglion, to the parotid). There is no meaningful sympathetic 'off switch' for volume: sympathetic firing adds protein and mucus but very little water, which is why a frightened mouth feels dry and sticky rather than simply empty. The acinus makes a plasma-like fluid; the duct then pulls sodium and chloride back out and adds potassium and bicarbonate, and because the duct wall will not let water follow, saliva arrives in the mouth dilute (hypotonic). Resting saliva sits close to neutral, around pH 6.5 to 7; as flow rises the duct has less time to strip it, bicarbonate climbs and saliva becomes alkaline — so buffering power is a function of flow rate. It carries mucins for lubrication, bicarbonate to neutralise acid, calcium and phosphate to rebuild enamel, and antimicrobials — IgA, lysozyme, lactoferrin.

The first phase of swallowing is voluntary and is mostly the tongue. Teeth and the muscles of mastication (trigeminal nerve, V3) cut and grind; the tongue (hypoglossal nerve, XII) mixes the food with saliva, gathers it into a single ball on its upper surface (the bolus) and holds it against the hard palate, sealed at the back by the tongue base against the soft palate. The lips and cheeks (facial nerve, VII) keep it in. Then the tongue strips backwards against the palate like a squeegee and throws the bolus into the oropharynx. Nothing further happens until sensation from the back of the mouth and pharynx reaches the brainstem and triggers the reflex.

The second phase is a reflex and takes about one second. Sensory fibres from the oropharynx and the entrance to the larynx (glossopharyngeal nerve, and the internal branch of the superior laryngeal nerve from the vagus) reach a pattern generator in the medulla (nucleus tractus solitarius feeding nucleus ambiguus), which fires a fixed motor sequence out through V, VII, IX, X and XII. Five things happen almost together: the soft palate lifts and shuts off the nose; the larynx is pulled upwards and forwards under the tongue base; the epiglottis tips backwards over the laryngeal inlet; the vocal cords close; and breathing stops for the duration (deglutitive apnoea, normally interrupting expiration, so the next breath out helps clear the entrance). The same forward-and-up movement of the larynx physically pulls open the upper oesophageal sphincter (cricopharyngeus), which relaxes at the same moment. If food does get past the cords, sensation from the larynx triggers a cough — the last line of defence.

What goes wrong

Dry mouth (xerostomia)Dental cariesOropharyngeal dysphagia (difficulty starting the swallow)Aspiration pneumonia and aspiration pneumonitisOral candidiasis (thrush)

What we give

Muscarinic agonists (salivary stimulants)Topical fluorideAntifungals for oral candidiasisBeta-lactam antibiotics for aspiration pneumonia

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 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.

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.

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.

What goes wrong

Gastro-oesophageal reflux disease (GORD)Barrett oesophagusAchalasiaOesophageal varices

What we give

Proton pump inhibitors (PPIs)Dihydropyridine calcium channel blocker (with nitrates as the alternative)Non-selective beta blockersVasopressin analogue (splanchnic vasoconstrictor)

The only organ that deliberately makes a strong acid and then has to survive it — so almost everything on this page is one of two stories: acid winning against a barrier that has been undermined, or decades of inflammation turning the lining into a cancer.

What it does

Parietal cells, packed into the glands of the upper two-thirds of the stomach (body and fundus), pump hydrogen ions into the lumen against a millionfold gradient using the H+/K+-ATPase — the proton pump — sitting in the membrane of a deep infolding called the secretory canaliculus. Three signals switch it on: acetylcholine from the vagus (M3 receptors), gastrin from the antrum (CCK2 receptors), and histamine from neighbouring enterochromaffin-like (ECL) cells (H2 receptors). Their wiring is not the same: gastrin's effect on acid is largely indirect, acting mainly on ECL cells to release histamine, which is why histamine is the amplifier of the system; acetylcholine acts directly on M3 receptors on the parietal cell itself (as well as on ECL cells), and vagal fibres also release gastrin-releasing peptide onto antral G cells. Whatever the signal, the pump is the last step. The same cell also makes intrinsic factor, the only carrier that gets vitamin B12 absorbed in the terminal ileum.

Acid at pH 1-2 with pepsin would digest the stomach itself. What stops it is a stack of defences: a sticky mucus layer holding bicarbonate against the surface so the epithelial cell membrane sits near pH 7, tight junctions between cells, an epithelium that patches damage within minutes to hours, and generous mucosal blood flow to wash away any acid that gets through. Prostaglandins, made locally by cyclo-oxygenase-1 (COX-1), maintain nearly all of it — mucus, bicarbonate, blood flow, repair — and restrain the parietal cell as well.

The stomach is really two organs. The body makes acid; the antrum makes gastrin. G cells in the antral lining release gastrin into the blood when peptides and amino acids arrive and when the vagus fires; gastrin drives ECL and parietal cells and also keeps the acid-secreting mucosa growing (a trophic effect). The off switch is acid itself: once luminal pH drops below about 3, antral D cells release somatostatin, which silences the G cell beside them. Acid turns off its own signal — a negative feedback loop.

What goes wrong

Peptic ulcer diseaseHelicobacter pylori infectionNSAID and aspirin ulcerationGastric adenocarcinomaAutoimmune atrophic gastritis and pernicious anaemia

What we give

Proton pump inhibitor (PPI)Histamine H2 receptor antagonistH pylori eradication therapy — PPI plus two antibiotics (triple therapy)Prostaglandin E1 analogue — misoprostol

Six metres of thin-walled tube folded into roughly 30 square metres of absorbing surface: wreck the surface and the patient starves in the middle of a meal, block the tube and they lose litres into it.

What it does

The lining is folded three times over — circular folds, then finger-like projections (villi), then a fuzz of microvilli on every cell (the brush border) — turning a tube of a few metres into roughly 30 square metres of absorbing surface.

Digestion is finished on the membrane itself. Enzymes stud the microvilli (lactase, sucrase-isomaltase, peptidases) and transporters sit beside them — and each nutrient has its own postcode: iron, calcium and folate in the duodenum and upper jejunum; vitamin B12 (bound to intrinsic factor) and bile salts almost entirely in the last 60-100 cm (terminal ileum).

About 7-9 L of fluid enters the small bowel daily (roughly 2 L swallowed, the rest saliva, gastric juice, bile, pancreatic juice and its own secretion) and it reabsorbs roughly 80% of that, passing 1-2 L to the colon; the epithelium is leaky, so water follows solute in whichever direction the osmotic gradient points.

What goes wrong

Coeliac diseaseLactase deficiency (adult hypolactasia and secondary loss)Terminal ileal disease — B12 and bile salt lossSmall bowel obstruction

What we give

Oral iron (ferrous sulfate, ferrous fumarate)Bile acid sequestrant (colestyramine)Vitamin B12 replacement (hydroxocobalamin, intramuscular)5-HT3 antagonist (ondansetron) — and why metoclopramide is the wrong drug here

A drying machine with a fermentation vat inside it: about 1.5 litres of watery ileal effluent arrives each day and 100-200 mL of formed stool leaves, while 10^11 bacteria per gram feed the lining and hold pathogens out. Nearly everything on this page is that machine failing in one of three ways — it stops drying (diarrhoea), the barrier between bacteria and immune system breaks (inflammatory bowel disease), or the crypt stem cells that rebuild the lining every few days acquire the wrong mutations (colorectal cancer).

What it does

About 1.5 litres of liquid leaves the ileum and enters the caecum each day; 100-200 mL leaves as stool. The colon does this by pumping sodium out of the lumen — electroneutral NaCl absorption in the proximal colon, and epithelial sodium channels (ENaC) in the distal colon that aldosterone switches on — while potassium is secreted the other way. Water follows the sodium osmotically; it is never pumped. Push the colon and it can absorb around 4-5 litres a day, so there is real reserve — but only if contents stay in contact with the wall long enough [colonic fluid and electrolyte reabsorption].

The colon is a fermenter. Bacteria break down fibre and any carbohydrate the small bowel missed into short-chain fatty acids — butyrate, propionate, acetate. Butyrate is the colonocyte's main fuel, absorbed straight from the lumen, and its absorption itself drags sodium and water with it. The resident flora also occupy the niche so pathogens cannot (colonisation resistance), make vitamin K2 (menaquinones), and split drugs the small bowel could not absorb [colonic microbiome and fermentation].

Colonic movement is mostly slow churning (haustral segmentation) that holds contents against the wall for hours, punctuated by one to three mass movements a day that sweep a whole segment forward — often triggered after a meal (gastrocolic reflex). The enteric nervous system runs this locally; mu-opioid receptors on myenteric neurons increase resting tone and suppress propulsion, and 5-HT from enterochromaffin cells drives it. When stool reaches the rectum, distension relaxes the internal anal sphincter automatically (rectoanal inhibitory reflex) and you feel the urge; the external sphincter is the voluntary part [colonic motility and defecation].

What goes wrong

Acute infective diarrhoeaClostridioides difficile colitisInflammatory bowel diseaseConstipation, including opioid-induced constipationColorectal cancer

What we give

Oral rehydration solution (glucose-electrolyte solution)Oral vancomycin (glycopeptide antibiotic) — and fidaxomicinAminosalicylates (5-ASA)Osmotic laxatives

The last 15 cm of gut is a storage tank with a two-part valve on the end, and a line drawn across the canal — the dentate line — that decides whether a problem there bleeds silently or hurts like nothing else; almost every anorectal complaint, and every drug on this page, comes back to sphincter pressure, stool consistency, or which side of that line you are on.

What it does

The rectum is normally empty. Stool arriving stretches the wall, and that stretch does two jobs at once. It tells you something has arrived (rectal sensation, carried up the pelvic splanchnic nerves, S2-4), and it triggers a local enteric reflex that relaxes the internal sphincter for a few seconds (rectoanal inhibitory reflex, RAIR) so the exquisitely sensitive lining just below the dentate line can taste the contents and tell gas from liquid from solid (sampling). If the moment is wrong, the rectum relaxes to take the volume (accommodation), the urge fades, and you can wait.

Two sphincters, two nervous systems. The internal anal sphincter is the thickened continuation of the bowel's own circular smooth muscle: involuntary, contracted all day and all night, and responsible for most of the resting closure pressure (roughly 55-70% of a resting pressure of about 40-70 mmHg on manometry, with normal ranges varying by technique). The external anal sphincter is skeletal muscle supplied by the inferior rectal branch of the pudendal nerve (S2-4), and the puborectalis sling is skeletal muscle supplied by direct sacral branches (S3-4, the nerve to levator ani) with a variable pudendal contribution: you can consciously clamp them shut, but maximal squeeze fatigues within about a minute. Puborectalis also hooks the anorectal junction forwards into a bend (the anorectal angle), which is a mechanical barrier in its own right.

The dentate line sits about 2 cm inside the anal verge, where hindgut endoderm meets proctodeal ectoderm, and everything changes across it. Above: columnar (then transitional) lining, autonomic (visceral) innervation with no somatic pain fibres, venous drainage by the superior rectal vein into the portal system, lymph upwards to internal iliac nodes (and, from the rectum above, along the superior rectal vessels to inferior mesenteric nodes). Below: squamous anoderm, supplied by the inferior rectal branch of the pudendal nerve and as pain-sensitive as any skin on the body, venous drainage into systemic inferior rectal veins, lymph to the superficial inguinal nodes.

What goes wrong

HaemorrhoidsAnal fissureFaecal incontinence from sphincter or pudendal nerve injuryFaecal impaction with overflow incontinenceRectal cancer presenting as haemorrhoids

What we give

Osmotic laxatives and bulking agentsTopical nitrate (chemical sphincterotomy), with topical calcium channel blocker as the alternativeTopical anorectal preparations: local anaesthetic with or without corticosteroidLoperamide

One organ does the body's protein synthesis, its drug metabolism, its ammonia disposal and its bilirubin excretion, and it does all of it on blood that has already passed through the gut — so when it scars you get bleeding, confusion, jaundice and ascites at once, and most of the drugs that treat it act somewhere other than the liver.

What it does

The liver makes the proteins that hold water inside blood vessels and stop bleeding. It makes about 10-15 g of albumin a day, which generates most of the oncotic pressure in plasma (half-life about 20 days). Hepatocytes make every clotting factor except von Willebrand factor (endothelium and platelets) and factor VIII, which comes mainly from liver sinusoidal endothelial cells rather than hepatocytes and so stays normal or high in liver disease. Factors II, VII, IX and X and the anticoagulant proteins C and S need vitamin K to be finished off (gamma-carboxylation), and factor VII has the shortest half-life of the lot — about 4-6 hours [hepatic synthetic function].

Everything absorbed from the gut meets the liver before it meets the rest of the body (first pass). Hepatocytes deal with drugs and toxins in two steps: phase I, mostly cytochrome P450 oxidation, which often produces a more reactive intermediate; then phase II conjugation — glucuronidation, sulfation, or attachment of glutathione — which makes it water-soluble enough to leave in bile or urine. Phase II pathways are saturable [hepatic drug metabolism].

Old red cells are broken down and their haem becomes bilirubin — about 300 mg (roughly 500 micromol) a day. It starts fat-soluble (unconjugated), travels stuck to albumin and cannot be filtered by the kidney. The liver conjugates it with glucuronic acid using the enzyme UGT1A1, which makes it water-soluble, then actively pumps it into bile (MRP2). That pumping step is the slowest step in the whole chain. In the gut, bacteria turn it into urobilinogen and then stercobilin, which is what makes stool brown [bilirubin conjugation and excretion].

What goes wrong

Cirrhosis and portal hypertensionHepatic encephalopathyJaundice — sorting the three patternsViral hepatitis B and CParacetamol hepatotoxicity and acute liver failure

What we give

Acetylcysteine (glutathione precursor)Non-absorbable disaccharide (osmotic laxative)Aldosterone (mineralocorticoid receptor) antagonistDirect-acting antivirals for hepatitis C

Every drop of blood from gut and spleen goes through the liver before it goes anywhere else. Scar the liver and that blood forces open old back-doors — so the patient bleeds, swells and becomes confused.

What it does

All blood leaving stomach, intestine, pancreas and spleen goes to the liver first, not straight to the heart. The superior mesenteric and splenic veins join behind the neck of the pancreas to form the portal vein, carrying roughly 1000-1200 mL/min and about 75% of the liver's blood supply (but only about half its oxygen). Ammonia is fed into the urea cycle, gut bacteria are taken up by Kupffer cells, and absorbed drugs are metabolised here before anything reaches the systemic circulation (first-pass metabolism).

The normal liver is a low-resistance sponge. Portal pressure is 5-10 mmHg and the pressure difference across the liver (hepatic venous pressure gradient, HVPG) is under 5 mmHg. That small gradient is the only thing driving flow, and the portal system has no valves anywhere.

At four sites, portal tributaries touch systemic veins (portosystemic anastomoses): the lower oesophagus (left gastric to azygos), around the umbilicus (paraumbilical to superficial epigastric veins), the anorectum (superior rectal to middle and inferior rectal), and the bare area and retroperitoneum. In health these channels carry almost nothing.

What goes wrong

Portal hypertension (usually from cirrhosis)Oesophageal varices and variceal haemorrhageAscitesHepatic encephalopathySpontaneous bacterial peritonitis

What we give

Non-selective beta blocker (propranolol, carvedilol)Terlipressin (vasopressin analogue)Aldosterone antagonist (spironolactone), with a loop diuretic added if neededLactulose (non-absorbable disaccharide)

A drainage system with a side-pocket: hepatocytes secrete bile continuously into ducts that converge as right and left hepatic ducts, then the common hepatic duct; the cystic duct hangs off it leading to the gallbladder, which stores and concentrates bile between meals; below that junction it is the common bile duct, which runs behind the first part of duodenum and then in a groove on the back of the head of pancreas, meets the pancreatic duct at the ampulla and empties into the second part of the duodenum through the sphincter of Oddi. Almost every disease on this page is one thing — a stone stuck somewhere — and where it sticks decides which illness the patient gets.

What it does

Bile is mostly water, with bile salts, phospholipid (mainly phosphatidylcholine), cholesterol, conjugated bilirubin and electrolytes. Cholesterol does not dissolve in water. It stays in solution only because bile salts and phospholipid wrap it into mixed micelles and vesicles, so what keeps bile liquid is a ratio, not a concentration: enough bile salt and phospholipid for the cholesterol present. Bile salts are also the osmotic engine that pulls water into the canaliculus (bile salt-dependent flow), so bile secretion is driven by the same molecules that keep it stable.

Between meals the sphincter of Oddi is tonically contracted, so most bile backs up the cystic duct into the gallbladder (the gallbladder still empties partially with each migrating motor complex, so filling between meals is not absolute). The gallbladder holds only about 30-50 mL, but it actively absorbs sodium out of the bile with water following, concentrating it five- to tenfold. It is a muscular bag with one narrow outlet — the cystic duct, roughly 3 mm wide with a spiral mucosal fold (valve of Heister) — and a dependent pouch at the neck (Hartmann pouch) where a stone naturally comes to rest.

Fat and amino acids arriving in the duodenum release cholecystokinin (CCK) from I cells. CCK contracts gallbladder smooth muscle through CCK1 receptors and relaxes the sphincter of Oddi, with vagal reinforcement, so concentrated bile squirts into the duodenum through the ampulla — which the pancreatic duct also drains into, a shared final common channel. Bile salts emulsify fat and carry the products, plus the fat-soluble vitamins A, D, E and K, to the brush border in micelles. About 95% of bile salts are then recaptured in the terminal ileum by a specific transporter (ASBT) and returned to the liver in the portal vein; the pool cycles about two to three times per meal, six to ten times a day (enterohepatic circulation).

What goes wrong

Gallstones (cholelithiasis) and biliary colicAcute cholecystitisCholedocholithiasis and obstructive (post-hepatic) jaundiceAscending cholangitisGallstone pancreatitis

What we give

Ursodeoxycholic acid (a hydrophilic bile acid)NSAIDs for biliary pain (with opioids as the step up)Antibiotics for biliary sepsisBile acid sequestrants for cholestatic itch

A gland that makes enough enzyme to digest a meal, or itself — so almost everything about it is a safety catch, and almost every disease here is a safety catch failing.

What it does

Acinar cells build the digestive enzymes and ship the protein-cutters out switched off (as zymogens, chiefly trypsinogen). They sit sealed in granules, are normally activated only in the duodenum by enteropeptidase (enterokinase) on the brush border, and any trypsin that fires early is mopped up by a built-in blocker (SPINK1) and by trypsin's own habit of cutting itself up.

Duct cells pour out a watery alkaline juice. CFTR in the apical membrane conducts both chloride and bicarbonate, and the chloride it recycles into the lumen drives SLC26 chloride/bicarbonate exchangers, so bicarbonate ends up in the duct with water dragged osmotically behind it. This neutralises stomach acid and flushes the enzymes downstream before they can settle.

The duodenum runs the gland by hormone. Acid arriving triggers secretin from S cells, which calls for the bicarbonate juice. Fat and protein arriving trigger cholecystokinin (CCK) from I cells, which calls for the enzyme-rich juice — largely through vagal reflexes — and squeezes the gallbladder.

What goes wrong

Acute pancreatitisChronic pancreatitisExocrine pancreatic insufficiencyCystic fibrosis pancreatic destruction

What we give

Pancreatic enzyme replacement therapy (pancrelipase / pancreatin, porcine)Proton pump inhibitorOpioid analgesics (mu receptor agonists)CFTR modulators (correctors plus a potentiator)

A two-layered serous membrane with two completely different nerve supplies — which is why the same disease produces vague central pain one hour and a rigid, finger-pointing abdomen the next.

What it does

The inner layer wrapping the organs (visceral peritoneum) is supplied by autonomic afferents that travel back with the sympathetics to the spinal cord. It cannot sense cutting or burning — its adequate stimuli are stretch, distension, traction, ischaemia and chemical or inflammatory irritation — and the brain can only localise it to the midline at the level of the embryonic gut segment: foregut to the epigastrium, midgut to the umbilicus, hindgut to the suprapubic region.

The outer layer lining the abdominal wall (parietal peritoneum) is supplied by the same segmental somatic nerves as the overlying skin and muscle — T7 to L1 for the wall, and the phrenic nerve (C3, C4, C5) for the central diaphragm. Somatic means sharp, precisely localised, and wired to a reflex arc back to the muscle of that same segment.

The cavity between the two layers is only a potential space holding a small volume of lubricating fluid — usually well under 50 mL — but the membrane itself has a very large surface area, classically quoted as roughly that of the skin (about 1.7 square metres), though direct anatomical measurements give a smaller figure. It exchanges water and solutes in both directions across the capillaries of the tissues it covers, and drains via one-way lymphatic gaps (stomata) in the diaphragm.

What goes wrong

Appendicitis and the migrating painPerforated viscus and generalised peritonitisAscites and spontaneous bacterial peritonitisAdhesions and small bowel obstruction

What we give

Antibiotics for secondary peritonitis (broad-spectrum beta-lactam, with or without a beta-lactamase inhibitor)Aldosterone antagonist (potassium-sparing diuretic)Intravenous albumin (colloid volume expander)Opioid analgesic (mu agonist)

The bowel runs itself on two nerve nets buried in its own wall — and when those nets are silenced by drugs and surgery, missing from birth, or no longer sweeping between meals, the gut behaves exactly as though it were blocked with nothing blocking it.

What it does

The gut wall carries its own nervous system, with roughly as many neurons as the spinal cord, arranged in two nets [enteric nervous system]. The outer net sits between the circular and longitudinal muscle layers and runs movement [myenteric plexus, or Auerbach plexus]; the inner net sits under the lining and runs secretion and local blood flow [submucosal plexus, or Meissner plexus]. Cut every nerve coming from the brain and the bowel still propels a bolus — sensory neurons in the wall detect stretch, interneurons relay, motor neurons act, all without leaving the gut [peristaltic reflex].

Peristalsis needs a push and a permission. Behind the bolus, excitatory motor neurons release acetylcholine and substance P and the circular muscle contracts. Ahead of it, inhibitory motor neurons release nitric oxide, vasoactive intestinal peptide (VIP) and ATP, and the muscle relaxes so the bolus has somewhere to go. Relaxation is an active nerve signal, not simply the absence of contraction.

The brain only modulates what the gut already does. Vagal cholinergic input speeds things up; sympathetic noradrenaline acting on presynaptic alpha-2 adrenoceptors, and mu-opioid receptors sitting on the same myenteric neurons, slow things down by cutting how much acetylcholine those neurons release. Whatever the input, acetylcholine acting on M3 muscarinic receptors of smooth muscle is the final common push, and dopamine acting on D2 receptors of the myenteric neurons is a standing brake on it.

What goes wrong

Postoperative ileusAcute colonic pseudo-obstruction (Ogilvie syndrome)Hirschsprung diseaseDiabetic gastroparesisSmall intestinal bacterial overgrowth

What we give

Dopamine D2 antagonist prokineticsMotilin receptor agonist — erythromycinAcetylcholinesterase inhibitor — neostigminePeripherally acting mu-opioid receptor antagonists (PAMORA)

Three unpaired arteries off the front of the aorta feed the entire gut in developmental blocks joined end to end by collaterals, and take about a quarter of the resting cardiac output: bowel dies where those territories meet, when one of them is suddenly plugged, or when the body decides the gut is the organ it can most afford to lose.

What it does

Three unpaired arteries leave the front of the aorta and divide the gut between them in developmental order. The coeliac trunk (about T12) supplies the foregut: lower oesophagus to the second part of the duodenum, plus liver, gallbladder, spleen and most of the pancreas. The superior mesenteric artery (SMA, about L1) supplies the midgut: duodenum beyond the bile duct opening, the whole small bowel, caecum, ascending colon and the proximal two thirds of the transverse colon. The inferior mesenteric artery (IMA, about L3) supplies the hindgut: distal transverse colon, descending and sigmoid colon and the upper rectum. The territories are joined end to end by collateral channels - pancreaticoduodenal arcades between coeliac and SMA, and along the colon the marginal artery of Drummond with the more central arc of Riolan between SMA and IMA. The joins are at their thinnest and most variable at the splenic flexure (Griffiths point) and the rectosigmoid junction (Sudeck point). The lower rectum has a second supply altogether, middle and inferior rectal arteries from the internal iliac.

The gut takes roughly 25 per cent of resting cardiac output, and SMA flow doubles or more within half an hour of a meal. Inside each villus the arteriole and venule run side by side as a hairpin, so oxygen short-circuits from artery to vein at the base and the oxygen tension falls progressively towards the tip (countercurrent exchange), leaving the tip the least well oxygenated tissue in the villus. The mucosa is also the hungriest layer of the bowel wall - it does the absorbing and turns its cells over every few days.

The splanchnic bed is also the body's blood reservoir and its first sacrifice. It holds about 20 to 25 per cent of the circulating volume in its veins, and its arterioles are packed with alpha-1 adrenoceptors and are unusually sensitive to angiotensin II and vasopressin. When blood pressure falls, sympathetic outflow clamps the gut down hard to defend the brain and heart.

What goes wrong

Acute mesenteric ischaemia (SMA embolus or thrombosis)Chronic mesenteric ischaemia (intestinal angina)Ischaemic colitisNon-occlusive mesenteric ischaemiaPortal hypertension and variceal bleeding

What we give

Systemic anticoagulation (unfractionated heparin infusion)Antiplatelet therapy (low-dose aspirin), alongside a statin and smoking cessationSplanchnic vasoconstrictorsNon-selective beta blockers

The gut does not absorb everything everywhere: sugars and amino acids along the length of the small bowel, iron in the duodenum, folate in the jejunum, fat wherever bile and lipase reach, and vitamin B12 only in the last stretch of ileum after a four-step relay that begins in the stomach — so a deficiency pattern is a map, and it points straight at the lesion.

What it does

Carbohydrate and protein are finished off and absorbed at the surface of the small bowel. The lining is folded, then villous, then carpeted in microvilli (brush border), giving roughly 30 m² of working surface. Enzymes sit on that brush border — lactase, sucrase-isomaltase, maltase-glucoamylase, peptidases — and hand the products straight to transporters beside them: glucose and galactose on a sodium-coupled carrier (SGLT1), fructose on a facilitated one (GLUT5), amino acids and di- and tripeptides on their own carriers (including PepT1). Most of this is done by mid-jejunum, so the distal small bowel is spare capacity (reserve length).

Fat will not dissolve in water, so it needs two things made outside the bowel wall. Pancreatic lipase (with colipase) splits triglyceride into fatty acids and monoglyceride; bile salts from the liver wrap those into tiny water-soluble parcels (micelles) that ferry them to the duodenal and jejunal brush border. Vitamins A, D, E and K ride in those same parcels. Absorbed long-chain fat is repackaged into chylomicrons and leaves in lymph, not portal blood — medium-chain fatty acids are the exception and go straight into portal blood without needing micelles. The bile salts themselves are reclaimed further down, in the terminal ileum, and recycled through the liver several times a day (enterohepatic circulation).

Iron is absorbed in one short stretch — the duodenum and the very top of the jejunum — and essentially nowhere else. Only the ferrous form (Fe2+) crosses on the apical carrier DMT1, and dietary ferric iron needs stomach acid and a brush border reductase (duodenal cytochrome b) to get there; haem iron from meat crosses by a separate route, still not fully worked out, and is absorbed several times more efficiently. The body has no regulated way of excreting iron — it leaks only through shed cells and bleeding — so absorption is the only control point. The liver hormone hepcidin binds and closes ferroportin, the exit door on the far side of the enterocyte, trapping iron in a cell that is shed into the stool a few days later. Inflammation drives hepcidin up.

What goes wrong

Coeliac diseaseExocrine pancreatic insufficiencyTerminal ileal disease or resection (Crohn disease)Pernicious anaemia and the loss of intrinsic factorIron deficiency anaemia — reading it back to the duodenum

What we give

Pancreatic enzyme replacementVitamin B12 replacementOral iron saltsBile acid sequestrant