Small intestine

What it normally 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.

  Explains coeliac disease: flatten the villi and a large part of that surface goes with them, along with the brush border enzymes and transporters sitting on it — so nutrients that were digested perfectly well are never absorbed.

• 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).

  Explains why the pattern of deficiency names the diseased segment, and why lactase — expressed most at the exposed tip of the villus — is the first thing lost after any injury.

• 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.

  Explains osmotic diarrhoea when sugar is left undigested, and the litres that vanish into a blocked bowel.

• Interstitial cells of Cajal are the pacemakers: they set the slow-wave rhythm that the enteric nervous system uses to drive segmentation (mixing) and slow peristalsis (propulsion). The tube is narrow — normally under about 3 cm — and its wall is thin.

  Explains obstruction: a narrow thin-walled tube distends fast, and once stretched the wall secretes instead of absorbing.

What goes wrong

• Coeliac disease← from “The lining is folded three times over — circul…”

  Gluten peptides (gliadin) survive digestion largely intact, reach the lamina propria and are deamidated there by tissue transglutaminase, which adds negative charge and makes them fit tightly into HLA-DQ2 or DQ8 on antigen-presenting cells. CD4 T cells respond and the mucosa is destroyed: villous atrophy, crypt hyperplasia, lymphocytes packed between the surface cells. The damage is worst proximally, in the duodenum — the exact stretch that absorbs iron, calcium and folate — and fades further down.

  Proximal disease equals proximal deficiencies: iron, folate, calcium (and so bone density). tTG IgA plus total IgA, biopsy on gluten, gluten-free diet for life; symptoms that persist usually mean hidden gluten, not refractory disease.

  You would find: A young adult with iron deficiency anaemia that will not correct on oral iron. Bloating, loose stool, weight that will not go on — or nothing at all. IgA tissue transglutaminase antibody is raised; always order total IgA with it, because selective IgA deficiency is over-represented in coeliac and gives a false negative. Both the serology and the duodenal biopsy must be done while the patient is still eating gluten, or both can be falsely normal. An intensely itchy blistering rash on elbows, knees and buttocks (dermatitis herpetiformis) is the same disease in the skin. About 1 in 70 Australians have it and most do not know.

• Lactase deficiency (adult hypolactasia and secondary loss)← from “Digestion is finished on the membrane itself. …”

  Lactase is expressed most at the tip of the villus, the most exposed part of the brush border. Most humans switch the gene down after weaning. On top of that, any mucosal injury — viral gastroenteritis, giardia, coeliac — shears the villus tips off and takes lactase with them. Undigested lactose is osmotically active and drags water into the lumen, then colonic bacteria ferment it into gas and short-chain fatty acids.

  Osmotic diarrhoea stops when the patient fasts; secretory diarrhoea does not. Lactase is the first enzyme lost after any small bowel insult and the last to come back — secondary lactase deficiency is temporary and does not mean lifelong dairy avoidance.

  You would find: Bloating, audible gurgling, wind and watery acidic stool 30 minutes to 2 hours after milk, settling when dairy stops and when the patient fasts. Stool pH low, stool osmotic gap high. Keeping lactase into adulthood is the northern European exception, not the rule: hypolactasia is usual in Aboriginal and Torres Strait Islander, Asian and Pacific Islander Australians, so lactose is a common and easily missed cause of diarrhoea dragging on in a child recovering from gastroenteritis.

• Terminal ileal disease — B12 and bile salt loss← from “Digestion is finished on the membrane itself. …”

  Crohn disease or a surgical resection takes out the last 60-100 cm of ileum. Two absorbing systems live there and effectively nowhere else. Lose the receptor for the intrinsic-factor-B12 complex and the liver's 3-5 year store of B12 slowly drains to a macrocytic anaemia and, if ignored, spinal cord damage. Lose the transporter that recycles bile salts and they spill into the colon, where they drive secretion — watery diarrhoea. After a longer resection (over about 100 cm) the whole bile salt pool falls, fat is no longer emulsified, and fat plus the fat-soluble vitamins are lost in the stool.

  Terminal ileum equals B12 plus bile salts. Short resection gives bile acid diarrhoea that a sequestrant fixes; long resection gives steatorrhoea that a sequestrant makes worse.

  You would find: Right iliac fossa pain and diarrhoea in a young adult. Pale, bulky, greasy stool that floats and will not flush (steatorrhoea). MCV high with hypersegmented neutrophils — though coexisting iron deficiency in Crohn can keep the MCV normal, so check B12 rather than relying on the index. Later, tingling feet and lost vibration and joint position sense (subacute combined degeneration of the cord). Where fat is malabsorbed and the colon is still in circuit, unabsorbed fat binds calcium in the lumen, which leaves oxalate free to be absorbed — hence the calcium oxalate kidney stones.

• Small bowel obstruction← from “Interstitial cells of Cajal are the pacemakers…”

  Adhesions from previous abdominal surgery are the commonest cause in Australia, then hernias, then tumour. Above the block the bowel distends with swallowed air and its own secretion. Stretch switches the wall from absorbing to secreting, so litres shift out of the circulation into the lumen and into the oedematous wall (third-spacing), and vomiting adds to the loss. As wall tension climbs past venous and then arterial pressure the segment becomes ischaemic, perforates and the patient goes septic. A closed loop — both ends blocked, as in a strangulated hernia or a volvulus — does this quickly.

  Colic, vomiting, distension, constipation. Drip and suck — nil by mouth, nasogastric tube, IV fluid with potassium — settles most adhesional obstruction. Pain that stops being colicky and becomes constant, with fever, tachycardia, rising lactate and tenderness, means strangulated bowel and a theatre call.

  You would find: Colicky central abdominal pain in waves, vomiting (early and bilious if proximal, later and faeculent if distal), distension and no flatus passed. Bowel sounds high-pitched and tinkling, then silent. Look for a surgical scar and put a hand on every hernia orifice. CT is the investigation of choice — it shows the transition point, the cause and any sign of ischaemia; plain films show dilated loops over 3 cm with fluid levels but do not exclude obstruction. Large-volume vomiting from a proximal obstruction strips hydrogen and chloride and gives a hypochloraemic, hypokalaemic metabolic alkalosis; a raised-anion-gap lactic acidosis instead is a red flag for ischaemic bowel, not the expected picture.

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.