Colon

What it normally 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].

  Explains why diarrhoea needs one of three things — small bowel delivery beyond the colon's roughly 5 L reserve, a damaged colonic wall, or transit so fast that absorption has no time to happen — why diarrhoea costs you potassium as well as water, and why every oral rehydration and laxative decision is really a decision about osmotic gradients.

• 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].

  Explains why an antibiotic course can be followed by diarrhoea and by Clostridioides difficile, why undigested lactose gives gas and cramps rather than just loose stool, and why some colonic drugs are activated by bacteria in the lumen.

• 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].

  Explains why transit time sets stool water content, why opioids constipate whoever takes them, why the urge comes after breakfast, and why an inflamed rectum produces urgency and tenesmus rather than volume.

• A single layer of columnar epithelium, a double layer of mucus (the inner one normally kept nearly free of bacteria), tight junctions and a dense mat of immune tissue underneath hold the largest bacterial population in the body away from the bloodstream. That epithelium is rebuilt continuously: stem cells at the base of each crypt divide and the surface is completely replaced every three to five days [colonic mucosal barrier and crypt turnover].

  Explains inflammatory bowel disease as a barrier-plus-immune failure against normal flora, and colorectal cancer as a stepwise mutation problem in the fastest-dividing cell population in the gut.

What goes wrong

• Acute infective diarrhoea← from “About 1.5 litres of liquid leaves the ileum an…”

  Two routes, both defeating the drying machine of physiology fact 0. Either the small bowel secretes more than the colon can ever absorb — cholera toxin and rotavirus NSP4 drive chloride, and therefore sodium and water, into the lumen at rates well beyond 5 L a day (secretory) — or the colonic mucosa itself is invaded and damaged, so it cannot absorb and it leaks blood and pus (inflammatory: Campylobacter, Salmonella, Shigella, enteroinvasive and Shiga-toxin-producing E. coli, Entamoeba). Osmotic diarrhoea is the third pattern: unabsorbed solute (lactose, a poorly absorbed laxative) holds water in the lumen and stops when the patient stops ingesting it.

  Diarrhoea is a volume-versus-capacity problem. Watery and huge and it keeps going when fasting means the small bowel is secreting; bloody and small and febrile means the colonic wall is invaded; stopping when the patient stops eating means osmotic.

  You would find: Secretory: large-volume watery stool, no blood, continues while fasting, patient is dry — tachycardic, sunken eyes, prolonged capillary refill, and often hypokalaemic with a normal anion gap metabolic acidosis from lost potassium and bicarbonate. Inflammatory (dysentery): smaller-volume bloody stool with fever, cramps and tenesmus. Australian context matters here: rotavirus vaccine is on the National Immunisation Program, but hospitalisation rates for gastroenteritis and dehydration in Aboriginal and Torres Strait Islander children in remote communities remain several times the national rate, with shigellosis, cryptosporidiosis and strongyloidiasis all over-represented — a housing, water and crowding problem presenting as a gut problem.

• Clostridioides difficile colitis← from “The colon is a fermenter. Bacteria break down …”

  Straight out of physiology fact 1. A broad-spectrum antibiotic — cephalosporins, clindamycin, fluoroquinolones, amoxicillin-clavulanate are the usual culprits — flattens the resident flora and with it colonisation resistance. C. difficile spores that were harmless passengers, or newly swallowed from a ward surface, germinate into the empty niche and release toxins A and B. These are glucosyltransferases: they inactivate Rho-family GTPases inside colonocytes, which collapses the actin cytoskeleton. Tight junctions fail, cells die, and a fibrinopurulent pseudomembrane forms over the ulcerated mucosa. The colon now neither absorbs nor holds a barrier.

  The antibiotic does not cause the infection directly — it clears the competition. That is why treatment is another antibiotic, why about one in four relapse, and why replacing the flora (faecal microbiota transplant) cures the ones antibiotics cannot.

  You would find: Watery, often foul, diarrhoea starting days to weeks after antibiotics (up to about eight weeks), with cramps, fever and a raised white cell count. Diagnosis is a stool assay — in Australia usually a two-step algorithm (a sensitive screen such as GDH or NAAT, then a toxin immunoassay) — and only on unformed stool, because up to about 1 in 20 healthy adults and far more inpatients are simply colonised, so a positive test on formed stool means nothing. Severe disease turns into toxic megacolon: the patient stops passing stool, the abdomen distends, colonic diameter exceeds 6 cm on abdominal X-ray, and they look septic. Falling diarrhoea in a sicker patient is a bad sign, not a good one.

• Inflammatory bowel disease← from “A single layer of columnar epithelium, a doubl…”

  The barrier of physiology fact 3 fails and the immune tissue underneath mounts a sustained response against normal luminal flora in a genetically susceptible person. In ulcerative colitis the inflammation is mucosal, starts at the rectum and spreads continuously and proximally, and is confined to the colon — the one exception being mild backwash ileitis in extensive pancolitis. In Crohn disease it is transmural and patchy, anywhere from mouth to anus, so it burrows: strictures, fistulas and abscesses. Ulcerated mucosa cannot absorb sodium and water, and a stiff inflamed rectum cannot store stool.

  UC is continuous, mucosal, rectum upwards, colon only (backwash ileitis aside). Crohn is patchy, transmural, mouth to anus, and complicates by burrowing. Bloody diarrhoea plus urgency plus a raised calprotectin in a 25-year-old is IBD until proven otherwise.

  You would find: Ulcerative colitis: bloody diarrhoea with urgency and tenesmus, worse at night, often for weeks before presentation. Crohn: right iliac fossa pain, weight loss, mouth ulcers, perianal fistulas or tags, and diarrhoea that may not be bloody. Both: young adult, extraintestinal signs (erythema nodosum, episcleritis, large-joint arthritis, and primary sclerosing cholangitis with UC). Faecal calprotectin is raised — the practical test that separates IBD from irritable bowel syndrome before scoping. Australia has one of the higher prevalences in the world, roughly 1 in 250 people. Acute severe colitis can go on to toxic megacolon (physiology fact 2 gone: the inflamed colon stops contracting and dilates).

• Constipation, including opioid-induced constipation← from “Colonic movement is mostly slow churning (haus…”

  Physiology fact 2 slowed down. Fewer or weaker mass movements mean stool spends longer against an absorptive surface that is still working perfectly, so more water is pulled out and the stool hardens. Anything that slows transit does it: low fibre and low fluid (less bulk to distend the wall and trigger propulsion), immobility, hypothyroidism, hypercalcaemia, hypokalaemia, anticholinergic drugs, and above all opioids acting on myenteric mu receptors — raising resting tone while suppressing propulsion, and increasing anal sphincter tone as well. Ignoring the call to stool repeatedly lets the rectum accommodate and blunts the urge.

  Constipation is a transit problem, not an absorption problem: the colon is doing its job for too long. Tolerance does not develop to opioid constipation the way it does to nausea and sedation, so a laxative is planned from the start of an opioid, not added later.

  You would find: Hard, infrequent, difficult stool with straining and incomplete evacuation; a palpable loaded left colon; hard stool in the rectum on examination — or an empty rectum, which points higher. In the frail or elderly, overflow diarrhoea around a faecal impaction masquerades as diarrhoea; treating that with loperamide makes it worse. New constipation in an adult over 50, especially with rectal bleeding, weight loss or iron deficiency, is not constipation until the colon has been looked at.

• Colorectal cancer← from “A single layer of columnar epithelium, a doubl…”

  The crypt stem cells of physiology fact 3 divide for a lifetime, and mutations accumulate in sequence: loss of APC starts an adenoma, KRAS drives it bigger, then further hits including 18q loss and p53 loss turn a dysplastic adenoma into an invasive carcinoma over roughly ten years (the adenoma-carcinoma sequence). A separate serrated pathway (BRAF, microsatellite instability) accounts for a minority, more often right-sided. The tumour bleeds slowly into the lumen and eventually narrows it. Where it sits decides how it presents: the right colon is wide and its contents liquid, so tumours there grow large and bleed silently; the left colon and rectum are narrower with formed stool, so they obstruct and bleed visibly.

  Ten years from adenoma to carcinoma is the whole basis of screening. Right colon bleeds and makes you anaemic; left colon obstructs and bleeds visibly.

  You would find: Right-sided: iron deficiency anaemia, fatigue, weight loss, sometimes a mass — an older adult with unexplained iron deficiency needs a colonoscopy. Left-sided and rectal: change in bowel habit, rectal bleeding, tenesmus, obstruction. Australia has among the highest incidence rates in the world and colorectal cancer is the second most common cause of cancer death here. The National Bowel Cancer Screening Program mails a free immunochemical faecal occult blood test (iFOBT) every two years to people aged 50-74, and since July 2024 people aged 45-49 can request one — screening works because it catches adenomas during that decade-long window. Incidence in people under 50 is rising, so age alone does not exclude it.

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.