GI Physiology
1. What this chapter covers, and how NEET PG actually tests it
Gastrointestinal physiology is tested through three recurring question shapes.
A secretion is abnormal, and you are asked which cell or hormone is responsible. A segment of gut is removed or diseased, and you are asked what the patient will become deficient in. Motility fails, and you are asked which neurons are missing.
All three are answered by knowing where things happen rather than by knowing lists.
The absorption map is the clearest example. Iron is absorbed in the duodenum and vitamin B12 in the terminal ileum, so a duodenal disease and an ileal resection produce entirely different deficiencies from the same-looking clinical picture of malabsorption.
This chapter covers gastric acid secretion, pancreatic and biliary secretion, motility, and absorption with bilirubin metabolism.
| In scope here | Deliberately out of scope |
|---|---|
| Parietal cell control, gut hormones, Zollinger-Ellison physiology | Endoscopic and surgical management (see Surgery) |
| Secretin and cholecystokinin actions, enterohepatic circulation | Detailed hepatology and cirrhosis (see Medicine) |
| Lower oesophageal sphincter, achalasia, migrating motor complex, Hirschsprung | Inflammatory bowel disease pathology (see Pathology) |
| Site-specific absorption, bilirubin handling, hereditary jaundices | Nutritional requirements and deficiency syndromes (see Biochemistry) |
2. Gastric acid secretion
2.1 Three stimuli converge on one pump
The parietal cell secretes hydrochloric acid through the hydrogen-potassium ATPase, the proton pump, on its apical membrane.
Three agonists stimulate it, each through a different receptor.
| Agonist | Source | Receptor | Second messenger |
|---|---|---|---|
| Acetylcholine | Vagus | M3 | Calcium |
| Gastrin | Antral G cells | CCK-B | Calcium |
| Histamine | Enterochromaffin-like cells | H2 | Cyclic AMP |
Histamine occupies a special position, and this is the most useful fact in the section.
Gastrin and acetylcholine both stimulate the parietal cell directly and stimulate the enterochromaffin-like cells to release histamine, which then amplifies the response.
Histamine is therefore the final common amplifier, which is why an H2 blocker reduces acid secretion driven by all three stimuli rather than only by histamine.
A proton pump inhibitor acts at the pump itself and is therefore more complete still, blocking the final step regardless of what stimulated it.
2.2 The brake, and the phases
Acid secretion is restrained by somatostatin from antral D cells.
Low luminal pH stimulates the D cells, which suppress gastrin release — a direct negative feedback loop that prevents runaway acidification.
Secretion occurs in three phases with roughly predictable contributions.
The cephalic phase, triggered by sight, smell and taste and mediated by the vagus, accounts for about 30%.
The gastric phase, triggered by distension and by peptides in the lumen, accounts for about 60% and is the largest.
The intestinal phase contributes the remaining 10%.
Note which other cells matter. Chief cells secrete pepsinogen, activated to pepsin by acid. Parietal cells also secrete intrinsic factor, and this is the one indispensable gastric secretion.
A patient can survive without acid but not without intrinsic factor, which is why total gastrectomy mandates lifelong vitamin B12 replacement.
2.3 Zollinger-Ellison syndrome as an applied test
A gastrinoma secretes gastrin autonomously, so the normal feedback described above is lost.
The diagnostic signature is a high gastrin level despite a high acid output, a combination that cannot occur physiologically since acid should suppress gastrin.
Note the contrast with atrophic gastritis, where gastrin is also high but acid is low — there the rise is an appropriate response to achlorhydria.
Two further features are examinable. Diarrhoea and steatorrhoea occur because the excess acid reaching the duodenum inactivates pancreatic lipase, which requires an alkaline environment.
And the secretin stimulation test is paradoxical: secretin normally inhibits gastrin release, but a gastrinoma responds by increasing it.
Roughly a quarter of gastrinomas occur as part of multiple endocrine neoplasia type 1.
3. Pancreatic and biliary secretion
3.1 Two hormones, two different pancreatic responses
The exocrine pancreas has two secretory compartments, and each is controlled by its own hormone.
Secretin is released by duodenal S cells in response to acid entering the duodenum.
It acts on ductal cells to produce a watery, bicarbonate-rich secretion that neutralises gastric acid, protecting the mucosa and creating the alkaline pH that pancreatic enzymes require.
Cholecystokinin is released by duodenal I cells in response to fat and amino acids.
It acts on acinar cells to release digestive enzymes, contracts the gallbladder, relaxes the sphincter of Oddi, and slows gastric emptying.
The pairing is logical rather than arbitrary. Acid arriving calls for bicarbonate; nutrients arriving call for enzymes and bile. Each hormone answers the specific problem its stimulus represents.
3.2 The other gut hormones worth knowing
| Hormone | Source | Main action |
|---|---|---|
| Gastrin | Antral G cells | Acid secretion, mucosal growth |
| Glucose-dependent insulinotropic polypeptide | K cells | Insulin release (an incretin), reduces acid |
| Motilin | M cells | Initiates the migrating motor complex |
| Vasoactive intestinal peptide | Enteric neurons | Smooth muscle relaxation, intestinal secretion |
| Somatostatin | D cells | Inhibits essentially every gut secretion |
Two of these have distinctive clinical footprints.
Motilin drives the housekeeper waves of fasting, and erythromycin is a motilin receptor agonist — which is why it is used as a prokinetic in gastroparesis and why gastrointestinal upset is its characteristic side effect.
A VIPoma produces the WDHA syndrome: watery diarrhoea, hypokalaemia and achlorhydria, all direct consequences of unopposed intestinal secretion and inhibited acid production.
Somatostatin's blanket inhibition is why its analogue octreotide is used across such disparate conditions — variceal bleeding, secretory tumours and acromegaly alike.
3.3 The enterohepatic circulation
Bile salts are synthesised from cholesterol in the liver, secreted into bile, and used to emulsify fat.
They are then actively reabsorbed in the terminal ileum and returned to the liver, a cycle that recovers roughly 95% of the pool with each pass.
That efficiency is what allows a relatively small bile salt pool to support digestion of a whole day's fat intake.
Terminal ileal disease or resection therefore has two separate consequences, and questions exploit both.
Bile salts escaping into the colon are converted by bacteria into agents that stimulate colonic secretion, causing bile salt diarrhoea.
And loss of the recirculated pool depletes bile salts faster than the liver can replace them, causing fat malabsorption with steatorrhoea and deficiency of the fat-soluble vitamins A, D, E and K.
Interrupting the same circulation deliberately is how bile acid sequestrants lower cholesterol — the liver must divert cholesterol into new bile salt synthesis, upregulating its low-density lipoprotein receptors.
4. Motility
4.1 The lower oesophageal sphincter and achalasia
Swallowing requires the lower oesophageal sphincter to relax at the right moment, and that relaxation is an active, inhibitory event.
It is mediated by myenteric inhibitory neurons releasing nitric oxide and vasoactive intestinal peptide.
Achalasia is the loss of exactly those inhibitory neurons.
Both consequences follow immediately. The sphincter fails to relax, and the oesophageal body loses its coordinated peristalsis, since the same inhibitory network sequences the wave.
So achalasia is not simply a tight sphincter — it is a failure of inhibition, which is why the barium study shows a dilated body tapering to a smooth bird-beak narrowing and why manometry shows aperistalsis alongside incomplete relaxation.
Chagas disease produces an identical picture by destroying the same neurons, which is why it appears in questions as a secondary cause.
Gastro-oesophageal reflux is the opposite failure — transient inappropriate relaxations of the same sphincter.
4.2 The migrating motor complex
Between meals, the gut is not quiescent. Cycles of contraction sweep from stomach to ileum roughly every 90 to 120 minutes, driven by motilin.
These housekeeper waves clear residual debris and bacteria distally.
Their clinical importance is what happens when they fail. Loss of the migrating motor complex, as in scleroderma or diabetic autonomic neuropathy, permits small intestinal bacterial overgrowth.
Eating abolishes the complex, which is why continuous feeding also predisposes to overgrowth.
4.3 Hirschsprung disease
Enteric ganglion cells derive from neural crest cells that migrate down the gut in a cranial-to-caudal direction.
Arrest of that migration leaves the distal segment aganglionic, lacking both the submucosal and myenteric plexuses.
Because migration proceeds downward, the aganglionic segment always includes the distal-most bowel and extends proximally for a variable distance — most commonly the rectosigmoid.
The counterintuitive point is which segment looks abnormal.
The aganglionic segment is narrow and contracted, because it has lost its inhibitory innervation and cannot relax. The proximal, normally innervated bowel dilates as it obstructs against it.
So the dilated bowel is the healthy bowel, and a biopsy taken from the dilated segment will be falsely reassuring. The diagnostic biopsy must come from the narrow distal segment.
Failure to pass meconium within 48 hours is the classic neonatal presentation, and there is a recognised association with Down syndrome.
5. Absorption and bilirubin
5.1 The site map
Absorption is regionally specialised, and the map is what converts a described resection into a predicted deficiency.
| Nutrient | Site | Note |
|---|---|---|
| Iron | Duodenum and upper jejunum | Absorbed as ferrous iron; regulated by hepcidin acting on ferroportin |
| Calcium | Duodenum | Vitamin D dependent |
| Folate | Jejunum | Depleted quickly, since stores are small |
| Vitamin B12 | Terminal ileum | Requires intrinsic factor |
| Bile salts | Terminal ileum | Active transport, enterohepatic recycling |
| Fat-soluble vitamins A, D, E, K | Small intestine, bile-dependent | Deficient whenever bile salts are lacking |
Two segments carry disproportionate clinical weight.
Duodenal disease, as in coeliac disease, characteristically produces iron deficiency, and folate deficiency follows if the jejunum is involved.
Terminal ileal disease, as in Crohn's disease, produces vitamin B12 deficiency and bile salt malabsorption together, because both processes share that segment exclusively.
The contrast is worth stating explicitly: a proximal problem gives iron and folate deficiency, a distal one gives B12 deficiency and steatorrhoea.
5.2 Bilirubin, and why the urine tells you the level
Haem is broken down to unconjugated bilirubin, which is water-insoluble and travels bound to albumin.
The liver conjugates it with glucuronic acid via UDP-glucuronosyltransferase, producing water-soluble conjugated bilirubin that is excreted in bile.
Only conjugated bilirubin can appear in urine, because only it is water-soluble and not albumin-bound.
That single property makes the urine a level-locating test.
| Type | Bilirubin raised | Urine bilirubin | Urine urobilinogen | Stools |
|---|---|---|---|---|
| Prehepatic (haemolysis) | Unconjugated | Absent | Raised | Normal |
| Hepatic | Mixed | Present | Variable | Normal or pale |
| Posthepatic (obstruction) | Conjugated | Present, dark urine | Absent | Pale |
Obstruction blocks bilirubin from reaching the gut, so no urobilinogen is formed and the stools lose their pigment — the two findings are the same fact seen from different ends.
5.3 The hereditary hyperbilirubinaemias
Four inherited disorders are tested, and they divide cleanly by which step fails.
Gilbert syndrome is a mild reduction in UDP-glucuronosyltransferase activity, giving an unconjugated hyperbilirubinaemia that becomes visible during fasting, illness or stress. It is benign and needs no treatment.
Crigler-Najjar type 1 is absence of the same enzyme, producing severe unconjugated hyperbilirubinaemia and kernicterus in the newborn. Type 2 is partial and responds to phenobarbitone, which induces the residual enzyme.
Dubin-Johnson syndrome is a defect in canalicular excretion of conjugated bilirubin, so the conjugated fraction rises and the liver appears black on biopsy from accumulated pigment.
Rotor syndrome is similar biochemically but the liver is not pigmented, which is the standard discriminator between the two.
Worked clinical vignettes
Q1. A patient has recurrent duodenal ulcers, diarrhoea and steatorrhoea. Serum gastrin is markedly raised and gastric acid output is high. What explains the steatorrhoea?
Pick an option to check your answer.
Show explanation
Solution. High gastrin with high acid output is a gastrinoma, since acid should otherwise suppress gastrin.
Pancreatic lipase functions only in an alkaline environment, normally created by secretin-driven bicarbonate. The overwhelming acid load inactivates it, so fat digestion fails.
The pancreas itself is structurally normal, which is why (a) is wrong. Answer: (b).
Q2. A patient has undergone terminal ileal resection for Crohn's disease. Which two problems should be anticipated, and why do they occur together?
Pick an option to check your answer.
Show explanation
Solution. The terminal ileum is the only site for intrinsic factor-mediated vitamin B12 absorption and for active bile salt reabsorption.
Losing it therefore produces B12 deficiency and, from depletion of the bile salt pool, fat malabsorption with steatorrhoea and fat-soluble vitamin deficiency.
(a) describes the pattern of proximal small bowel disease such as coeliac disease. Answer: (b).
Q3. A neonate has failed to pass meconium at 60 hours and has abdominal distension. Contrast study shows a narrow distal segment with dilated bowel proximally. Where should the diagnostic biopsy be taken from, and why?
Pick an option to check your answer.
Show explanation
Solution. In Hirschsprung disease, neural crest migration arrests, leaving the distal bowel aganglionic.
Without inhibitory innervation that segment cannot relax, so it is narrow and contracted, while the normally innervated proximal bowel dilates as it obstructs against it.
The dilated bowel is therefore the healthy bowel, and biopsying it would be falsely reassuring. Answer: (b).
7. Common exam traps
- Treating histamine as just one of three stimuli. It is the final common amplifier, which is why H2 blockade reduces acid driven by gastrin and vagal input too.
- Assuming a high gastrin always means a gastrinoma. Atrophic gastritis also raises gastrin, but with low acid; it is the combination with high acid that is pathological.
- Forgetting intrinsic factor after gastrectomy. Acid is dispensable, intrinsic factor is not.
- Reversing secretin and cholecystokinin. Acid triggers secretin for bicarbonate; fat and amino acids trigger cholecystokinin for enzymes and bile.
- Describing achalasia as a tight sphincter. It is loss of inhibitory neurons, which is why peristalsis fails as well as relaxation.
- Biopsying the dilated bowel in Hirschsprung disease. The contracted distal segment is the aganglionic one.
- Confusing proximal and distal malabsorption patterns. Duodenum and jejunum give iron and folate deficiency; terminal ileum gives B12 deficiency with steatorrhoea.
- Expecting bilirubinuria in haemolysis. Unconjugated bilirubin is albumin-bound and water-insoluble, so it cannot enter urine.
Summary
- Acetylcholine, gastrin and histamine all stimulate the parietal cell, but histamine is the final common amplifier, which is why H2 blockade reduces all three inputs.
- Somatostatin from D cells provides negative feedback, since low luminal pH suppresses gastrin release.
- Cephalic, gastric and intestinal phases contribute roughly 30, 60 and 10 per cent of acid secretion.
- Intrinsic factor is the only indispensable gastric secretion, so gastrectomy requires lifelong vitamin B12 replacement.
- Zollinger-Ellison syndrome is defined by high gastrin with high acid output, causes steatorrhoea by inactivating pancreatic lipase, and shows a paradoxical rise in gastrin after secretin.
- Secretin responds to acid and drives ductal bicarbonate; cholecystokinin responds to fat and amino acids and drives acinar enzymes, gallbladder contraction and sphincter relaxation.
- Motilin drives the migrating motor complex and is mimicked by erythromycin; a VIPoma causes watery diarrhoea, hypokalaemia and achlorhydria.
- Bile salts recirculate through the terminal ileum with about 95% efficiency, which is why ileal disease causes both bile salt diarrhoea and steatorrhoea.
- Lower oesophageal sphincter relaxation is an active inhibitory event using nitric oxide and vasoactive intestinal peptide, and achalasia is the loss of those neurons, producing aperistalsis as well as failed relaxation.
- The migrating motor complex clears the gut between meals, and its loss permits small intestinal bacterial overgrowth.
- Hirschsprung disease arises from arrested craniocaudal neural crest migration, so the aganglionic segment is the narrow distal one and the dilated bowel is normal.
- Iron and calcium are absorbed in the duodenum, folate in the jejunum, and vitamin B12 and bile salts in the terminal ileum.
- Proximal small bowel disease gives iron and folate deficiency; terminal ileal disease gives B12 deficiency with steatorrhoea and fat-soluble vitamin loss.
- Only conjugated bilirubin is water-soluble, so bilirubinuria excludes a purely prehepatic cause.
- Obstruction produces dark urine with pale stools and absent urobilinogen, all consequences of bilirubin failing to reach the gut.
- Gilbert and Crigler-Najjar syndromes are conjugation defects giving unconjugated hyperbilirubinaemia; Dubin-Johnson and Rotor are excretion defects giving conjugated hyperbilirubinaemia, distinguished by the black liver of Dubin-Johnson.
