Gut histology
Gut histology from oesophagus to colon; liver, gallbladder and pancreas
Histology of the oesophagus, stomach, intestines, liver, gallbladder and pancreas for FCPS Part 1, with the features that identify each organ. Covers gastric cell products, liver zones, Kupffer and stellate cells, metaplasia and key biopsy findings.
The four-layer plan
- Mucosa: epithelium, lamina propria, muscularis mucosae.
- Submucosa: connective tissue, larger vessels, Meissner (submucosal) plexus controlling secretion and local blood flow; glands in the oesophagus and duodenum.
- Muscularis externa: inner circular and outer longitudinal layers with the Auerbach (myenteric) plexus between them controlling motility.
- Serosa on intraperitoneal parts, adventitia on the oesophagus and retroperitoneal parts.
The plan is the same everywhere; the epithelium and glands change to match each organ's job, which is how a slide is identified.
Organ by organ
| Organ | Epithelium | Identifying features |
|---|---|---|
| Oesophagus | Stratified squamous non-keratinised | Submucosal mucous glands; skeletal muscle above, smooth below; adventitia, no serosa |
| Stomach, fundus and body | Simple columnar mucous cells (no goblet cells) | Rugae; gastric pits leading to straight glands with parietal and chief cells; extra oblique muscle layer |
| Stomach, antrum | Simple columnar | Deep pits, mucous glands, G cells (gastrin), D cells (somatostatin) |
| Duodenum | Columnar with brush border and goblet cells | Brunner glands in the submucosa secreting alkaline mucus and bicarbonate |
| Jejunum | Same | Tall leaf-like villi, prominent plicae circulares, no Brunner glands or large Peyer patches |
| Ileum | Same, more goblet cells | Peyer patches in mucosa and submucosa, with M cells over them |
| Colon | Columnar with very many goblet cells | No villi, straight test-tube crypts; taeniae coli |
| Appendix | Colonic type | Ring of lymphoid follicles |
| Anal canal | Columnar above the pectinate line, stratified squamous below | Transition zone at the pectinate line |
Gastric gland cells
| Cell | Location | Product |
|---|---|---|
| Parietal (oxyntic) | Body and fundus, upper gland; pink, many mitochondria | HCl and intrinsic factor |
| Chief (zymogenic) | Body and fundus, gland base; basophilic | Pepsinogen, gastric lipase |
| Mucous neck cells | Gland neck | Soluble mucus; stem cells nearby |
| ECL cells | Body | Histamine (stimulates parietal cells) |
| G cells | Antrum | Gastrin |
- HCl activates pepsinogen to pepsin, kills swallowed microbes and frees iron and vitamin B12 from food. Autoimmune gastritis destroys parietal cells in the body and fundus, causing achlorhydria and pernicious anaemia (no intrinsic factor), with antral sparing and high gastrin.
- Zollinger–Ellison syndrome: a gastrinoma drives parietal cell hyperplasia and acid hypersecretion.
Small intestine cells
- Enterocytes with a microvillus brush border carrying disaccharidases (lactase).
- Goblet cells; Paneth cells at crypt bases (lysozyme, defensins); stem cells in crypts (renewal every 3–5 days).
- Enteroendocrine cells: I cells (CCK, duodenum and jejunum), S cells (secretin, duodenum), K cells (GIP).
Biopsy findings to know
| Condition | Histology |
|---|---|
| Barrett oesophagus | Squamous replaced by columnar epithelium with goblet cells (intestinal metaplasia) above the GE junction; adenocarcinoma risk |
| H. pylori gastritis | Antral inflammation, intestinal metaplasia; gastric cancer and MALT lymphoma risk |
| Coeliac disease | Villous atrophy, crypt hyperplasia, intraepithelial lymphocytes in duodenal biopsy |
| Whipple disease | PAS-positive foamy macrophages in the lamina propria |
| Collagenous colitis | Normal colonoscopy but a thickened subepithelial collagen band (over 10 micrometres); chronic watery diarrhoea in older women; linked to PPIs (lansoprazole), NSAIDs, SSRIs |
| Lymphocytic colitis | More than 20 intraepithelial lymphocytes per 100 epithelial cells, normal collagen band |
| Ulcerative colitis | Crypt abscesses, crypt distortion, mucosa only |
| Hirschsprung disease | No ganglion cells in either plexus |
Liver
- Classic lobule: hexagon around a central vein, with portal triads (portal vein branch, hepatic artery branch, bile ductule) at the corners. Blood flows from triad to central vein; bile flows the other way, from bile canaliculi between hepatocytes to canals of Hering and bile ducts.
- Acinus zones: zone 1 (periportal) gets the most oxygen and nutrients and is hit first by toxins arriving in portal blood (phosphorus) and in viral hepatitis; zone 3 (centrilobular) has the least oxygen and the most cytochrome P450, so it suffers first in ischaemia, right heart failure (nutmeg liver), paracetamol and alcohol.
- Sinusoids have fenestrated, discontinuous endothelium with no basement membrane.
- Kupffer cells are resident macrophages (monocyte lineage) in sinusoids that clear particles, bacteria and old red cells.
- Space of Disse lies between endothelium and hepatocytes; its stellate (Ito) cells store vitamin A and, when activated by injury, become myofibroblasts that lay down collagen, causing fibrosis and cirrhosis.
- Hepatocytes have abundant smooth ER (drug metabolism, lipoprotein assembly with the Golgi) and rough ER (albumin, clotting factors).
| Finding | Meaning |
|---|---|
| Ground-glass hepatocytes | Finely granular, pale pink cytoplasm full of HBsAg in smooth ER: chronic hepatitis B |
| Mallory–Denk bodies | Clumped keratin in ballooned hepatocytes: alcoholic and non-alcoholic steatohepatitis |
| Clear cytoplasmic spaces | Fat droplets (steatosis), alcohol or metabolic |
| Councilman bodies | Apoptotic hepatocytes in acute viral hepatitis |
| Fibrosis and portal inflammation | Mark chronicity in chronic hepatitis |
Gallbladder
- Simple tall columnar epithelium with microvilli, thrown into folds; no goblet cells, no muscularis mucosae and no submucosa; a layer of smooth muscle and adventitia or serosa.
- Distinguishing it from colon: the colon has crypts packed with goblet cells, a muscularis mucosae and submucosa.
- It concentrates bile by absorbing sodium and water. Rokitansky–Aschoff sinuses are mucosal outpouchings in chronic cholecystitis; gastric or intestinal metaplasia may appear.
Pancreas
- Exocrine acini: serous cells with apical eosinophilic zymogen granules and a basophilic base; pale centroacinar cells (start of the intercalated duct) secrete bicarbonate; no myoepithelial cells, no striated ducts.
- Islets of Langerhans: pale endocrine clusters, most numerous in the tail. β cells (insulin, about 70%, central), α cells (glucagon, peripheral), δ cells (somatostatin), PP cells (pancreatic polypeptide, mainly in the head).
- Told apart from the parotid by its islets and centroacinar cells; the parotid has striated ducts.
Remember Brunner in the duodenum, plicae in the jejunum, Peyer in the ileum, goblet cells and no villi in the colon.
Exam trap Zone 3 of the liver acinus is damaged first by ischaemia and paracetamol; zone 1 by toxins in portal blood.
Exam trap The gallbladder has no submucosa, no muscularis mucosae and no goblet cells.
How FCPS asks about this
- Submucosal glands identifying the duodenum: Brunner glands, secreting alkaline mucus.
- Parietal cell products and site of loss in pernicious anaemia: HCl and intrinsic factor; body and fundus.
- Nature of Kupffer cells: resident macrophages of the sinusoids; stellate cells store vitamin A and cause fibrosis.
- Pale granular hepatocytes in chronic hepatitis B: ground-glass cells full of HBsAg.
- Part of pancreas with most islets: tail.
- Chronic watery diarrhoea on PPI and NSAID with normal colonoscopy: collagenous colitis; thick subepithelial collagen band.
- Gallbladder versus colon on a slide: gallbladder lacks goblet cells, crypts and submucosa.
Test yourself on this topic
5 of the 24 questions in our bank on this topic. Choose an answer to see why every option is right or wrong.
Which part of the stomach contains most of the G cells that secrete gastrin?
Answer: Antrum
The body and fundus contain oxyntic glands with parietal cells (HCl and intrinsic factor), chief cells (pepsinogen) and ECL cells (histamine). The antrum contains pyloric glands with G cells (gastrin) and D cells (somatostatin). Gastrin stimulates ECL cells to release histamine and parietal cells to secrete acid; it is released by peptides, vagal stimulation (via GRP) and gastric distension, and inhibited by low antral pH. Antrectomy removes the gastrin source; retained antrum after Billroth II causes high gastrin.
Gastric glands
- Body/fundus: parietal (HCl, IF), chief (pepsinogen), ECL
- Antrum: G cells (gastrin), D cells
- Gastrin → ECL histamine → acid
Remember G cells guard the gate (antrum).
Why the other options are wrong
- Fundus Parietal and chief cells.
- Body Parietal and chief cells.
- Cardia Mucous glands.
- Lesser curvature of the body only Not correct.
On histology, the gallbladder wall differs from the rest of the gut tube because it lacks which layers?
Answer: Muscularis mucosae, submucosa
The gallbladder has a tall columnar mucosa thrown into folds, a lamina propria, a layer of smooth muscle and a perimuscular connective tissue, but no muscularis mucosae and no submucosa. Outpouchings of mucosa into the muscle are called Rokitansky–Aschoff sinuses and increase in chronic cholecystitis. It concentrates bile by absorbing water and salt.
Gallbladder histology
- No muscularis mucosae
- No submucosa
- Tall columnar epithelium
- Rokitansky–Aschoff sinuses in cholecystitis
Remember Gallbladder skips two gut layers.
Exam trap Lack of submucosa lets inflammation and cancer reach the liver early.
Why the other options are wrong
- Mucosa and serosa It has both mucosa and (on its free surface) serosa.
- Muscle layer (externa) It has a muscle layer.
- Lamina propria and glands It has a lamina propria.
- Columnar epithelium It has a columnar epithelium.
A newborn has not passed meconium by 48 hours and has abdominal distension; rectal examination releases a gush of stool. A rectal suction biopsy is taken, sampling mucosa and submucosa only. Absence of ganglion cells in which structure confirms the diagnosis?
Answer: Submucosal (Meissner) plexus
Hirschsprung disease results from failed migration of neural crest cells to the distal bowel, so the affected segment lacks ganglion cells in both the submucosal and myenteric plexuses and cannot relax. Suction biopsy samples only mucosa and submucosa, so the diagnosis rests on absent ganglion cells in the submucosal plexus. Hypertrophied nerve trunks and increased acetylcholinesterase staining support it. The myenteric plexus can only be assessed on full-thickness biopsy.
Hirschsprung biopsy
- Neural crest fails to reach distal bowel
- Suction biopsy: mucosa + submucosa
- Look for absent submucosal ganglia
- Raised acetylcholinesterase fibres
Remember Suction biopsy sees the submucosal plexus.
Exam trap The dilated bowel is normal; the narrow distal segment is the diseased part.
Why the other options are wrong
- Myenteric (Auerbach) plexus Also aganglionic, but lies between muscle layers, beyond a suction biopsy.
- Lamina propria Contains no ganglion cells normally.
- Muscularis mucosae A thin muscle layer, not a nerve plexus.
- Serosal nerve fibres Not sampled and not diagnostic.
A 68-year-old woman taking lansoprazole and regular naproxen has had 3 months of watery, non-bloody diarrhoea 6–8 times a day, including at night. Colonoscopy looks normal, but biopsies are taken. Which of the following findings would confirm the most likely diagnosis?
Answer: Thickened subepithelial collagen band
Chronic watery diarrhoea in an older woman with a normal-looking colon suggests microscopic colitis, which is diagnosed only on biopsy. In collagenous colitis the band of collagen under the surface epithelium is thickened to more than 10 µm, with raised lamina propria inflammation; in lymphocytic colitis there are more than 20 intraepithelial lymphocytes per 100 epithelial cells. Drugs such as PPIs, NSAIDs and SSRIs are recognised triggers. Treatment is to stop the drug and give budesonide.
Microscopic colitis
- Watery diarrhoea, normal colonoscopy
- Collagenous: band > 10 µm
- Lymphocytic: IELs > 20/100
- Triggers: PPI, NSAID, SSRI; treat with budesonide
Remember Normal-looking colon with watery diarrhoea: always biopsy.
Exam trap Do not label chronic watery diarrhoea as irritable bowel in an older patient before colonic biopsies are taken.
Why the other options are wrong
- Crypt abscesses with goblet cell loss That is ulcerative colitis, which looks inflamed at colonoscopy.
- Transmural non-caseating granulomas That is Crohn disease, which usually shows ulcers.
- Villous atrophy with crypt hyperplasia That is coeliac disease, seen in duodenal, not colonic, biopsies.
- Flask-shaped ulcers with trophozoites That is amoebic colitis, which gives bloody stools and visible ulcers.
What is the main function of Brunner's glands in the duodenal submucosa?
Answer: Secrete alkaline mucus
Brunner's glands lie in the submucosa of the duodenum (a feature that identifies it on histology) and secrete bicarbonate-rich mucus that neutralises acid chyme and protects the mucosa. Their output rises with vagal stimulation and secretin, and falls with sympathetic activity, which may help explain ulcers in stress. Secretin itself comes from S cells.
Brunner's glands
- Duodenal submucosa
- Secrete alkaline mucus
- Neutralise acid
- Identify the duodenum
Remember Brunner buffers the acid.
Exam trap Brunner's glands lie in the submucosa; most gut glands are mucosal.
Why the other options are wrong
- Secrete pepsinogen Chief cells of the stomach.
- Absorb dietary iron Duodenal enterocytes do this.
- Produce the hormone secretin S cells.
- Secrete lysozyme and defensins Paneth cells.
Where this sits in the CPSP syllabus
- Paper 1: General and special histology, Gut histology: oesophagus to colon; liver, gallbladder, pancreas
- Surgery & Allied, Paper 2: Histology for surgery, Gut histology: oesophagus to colon; liver, gallbladder, pancreas
- Medicine & Allied, Paper 2: Histology: liver, pancreas, spleen, kidney, brain, gut, Gut histology: oesophagus to colon; liver, gallbladder, pancreas
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