16.4 Gastrointestinal & Hepatobiliary Physiology
Key Takeaways
Salivation is driven mainly by parasympathetic input from cranial nerves VII and IX; swallowing has a voluntary oral phase followed by a reflex pharyngeal phase coordinated by the medulla and an esophageal phase that relaxes the lower esophageal sphincter through nitric oxide and VIP.
Parietal cells secrete HCl and intrinsic factor in response to acetylcholine (M3), gastrin (CCK-B) and histamine (H2), and the final common step is the H+/K+-ATPase that proton pump inhibitors block.
Secretin stimulates pancreatic bicarbonate secretion, CCK stimulates gallbladder contraction and pancreatic enzyme release, GIP and GLP-1 mediate the incretin effect, and motilin drives the migrating motor complex.
Iron is absorbed in the duodenum (regulated by hepcidin-ferroportin), calcium mainly in the duodenum with vitamin D, and vitamin B12 with intrinsic factor and bile acids in the terminal ileum.
The liver conjugates bilirubin, synthesizes albumin and most clotting factors, maintains fasting glucose, forms urea and clears many drugs by first-pass metabolism.
16.4 Gastrointestinal & Hepatobiliary Physiology
The physiology outline lists gastrointestinal physiology: hepatic, intestinal, stomach, gallbladder, salivation and swallowing. These mechanisms explain how proton pump inhibitors, NSAIDs, metformin and bariatric surgery affect nutrient absorption, why vitamin B12 and vitamin D deficiencies develop, and why liver disease changes drug handling and bleeding risk.
Organization and Control
- Enteric nervous system: the myenteric (Auerbach) plexus controls motility and the submucosal (Meissner) plexus controls secretion and blood flow. Both function semi-independently.
- Extrinsic nerves: parasympathetic (vagus; pelvic nerves for the distal colon) generally stimulates secretion and motility, and sympathetic input inhibits them.
- Slow waves set by the interstitial cells of Cajal determine maximal contraction frequency; action potentials on the wave crests trigger contraction.
- During fasting, the migrating motor complex sweeps debris aborally about every 90–120 minutes under motilin control. Erythromycin is a motilin receptor agonist (12.3).
Gastrointestinal Hormones
| Hormone | Source | Stimulus | Main actions |
|---|---|---|---|
| Gastrin | G cells (gastric antrum) | Peptides, gastric distension, vagal GRP | Increases acid secretion (CCK-B receptors, ECL histamine release), mucosal growth |
| Somatostatin | D cells | Acid in the lumen | Inhibits gastrin, acid and most GI hormones |
| Cholecystokinin (CCK) | I cells (duodenum, jejunum) | Fatty acids, amino acids | Gallbladder contraction, sphincter of Oddi relaxation, pancreatic enzyme secretion, slows gastric emptying |
| Secretin | S cells (duodenum) | Acid in the duodenum | Pancreatic and biliary bicarbonate secretion; inhibits gastric acid |
| GIP | K cells | Glucose, fat | Incretin (glucose-dependent insulin release) |
| GLP-1 | L cells (ileum, colon) | Nutrients | Incretin, glucagon suppression, slowed gastric emptying, satiety (basis for GLP-1 drugs, 12.2) |
| Motilin | M cells | Fasting | Migrating motor complex |
Salivation and Swallowing
- Saliva (about 1–1.5 L/day) is hypotonic, with low Na+ and Cl- and high K+ and HCO3-. It contains salivary amylase (starch digestion), lingual lipase, mucins, lysozyme, lactoferrin and IgA. Secretion is controlled mainly by the parasympathetic system (CN VII to the submandibular and sublingual glands; CN IX to the parotid), which produces abundant watery saliva. Anticholinergic drugs cause dry mouth (10.2).
- Swallowing has three phases:
- Oral phase (voluntary): the tongue pushes the bolus back.
- Pharyngeal phase (reflex): coordinated by the medullary swallowing center; the soft palate elevates, the larynx rises, the epiglottis covers the airway and the upper esophageal sphincter relaxes.
- Esophageal phase: primary peristalsis moves the bolus while the lower esophageal sphincter (LES) relaxes through vagal inhibitory neurons that release nitric oxide and VIP. Failure of LES relaxation with loss of peristalsis is achalasia.
The Stomach
| Cell | Product | Regulation and notes |
|---|---|---|
| Parietal (oxyntic) cells | HCl and intrinsic factor | Stimulated by acetylcholine (M3), gastrin (CCK-B) and histamine (H2); all converge on the H+/K+-ATPase (blocked by PPIs). The basolateral HCO3-/Cl- exchanger causes the postprandial alkaline tide |
| Chief cells | Pepsinogen (activated to pepsin below about pH 3), gastric lipase | Vagal stimulation |
| Mucous neck and surface cells | Mucus and bicarbonate | Protected by prostaglandins (lost with NSAIDs) |
| ECL cells | Histamine | Gastrin and vagal stimulation |
| G and D cells | Gastrin and somatostatin | Antral feedback control |
Phases of acid secretion:
- Cephalic phase (about 30%): sight, smell and taste of food act through the vagus.
- Gastric phase (about 60%): distension and peptides stimulate gastrin.
- Intestinal phase: a small contribution.
Gastric emptying depends on meal composition. Liquids empty fastest and fat slowest, because duodenal fat and acid trigger CCK, secretin and neural feedback. Diabetic gastroparesis (vagal autonomic neuropathy) causes early satiety, vomiting and erratic glucose control.
Pancreas, Gallbladder and Liver
- Exocrine pancreas: acinar cells secrete enzymes (stimulated by CCK and the vagus) and ductal cells secrete bicarbonate-rich fluid (stimulated by secretin). Trypsinogen is activated by brush-border enteropeptidase, and trypsin then activates the other zymogens.
- Bile: hepatocytes secrete bile acids, phospholipids, cholesterol and conjugated bilirubin. The gallbladder concentrates bile between meals and contracts in response to CCK. Bile acids form micelles for fat absorption and about 95% are reabsorbed in the terminal ileum (enterohepatic circulation). Ileal resection or disease causes bile acid diarrhea, fat malabsorption and B12 deficiency.
- Liver functions:
- Synthesis: albumin and most clotting factors (II, VII, IX, X need vitamin K)
- Glucose homeostasis: glycogen storage and gluconeogenesis
- Urea cycle detoxifies ammonia
- Bilirubin conjugation (UGT1A1; 18.4)
- Cholesterol and lipoprotein metabolism
- Drug metabolism, including first-pass extraction of portal blood (10.1)
Digestion and Absorption
| Nutrient | Digestion | Absorption |
|---|---|---|
| Carbohydrates | Amylase, then brush-border disaccharidases (lactase, sucrase, maltase) | Glucose and galactose via SGLT1 (Na+-coupled); fructose via GLUT5; exit through GLUT2 |
| Proteins | Pepsin, trypsin, chymotrypsin, carboxypeptidases | Amino acids via Na+-coupled transporters; di- and tripeptides via PepT1 |
| Fats | Lipases with bile-salt micelles | Re-esterified into triglycerides, packaged into chylomicrons and exported into lacteals (lymph) |
| Iron | Ferric iron reduced to ferrous; heme iron absorbed separately | Duodenum (DMT1 at the apical membrane, ferroportin at the basolateral membrane); hepcidin degrades ferroportin and blocks absorption |
| Calcium | Duodenum (active, calcitriol-dependent) plus passive absorption along the small bowel | |
| Folate | Jejunum | |
| Vitamin B12 | Released from food by acid and pepsin; binds R-binder, then intrinsic factor | Terminal ileum |
| Fat-soluble vitamins A, D, E, K | Require micelles | Small intestine, so they are lost in fat malabsorption |
| Water and electrolytes | Most in the small intestine; the colon absorbs Na+ and water and secretes K+ |
Tip
Long-term PPIs reduce acid-dependent release of vitamin B12 and the absorption of iron, calcium and magnesium. Metformin reduces B12 absorption, and bariatric surgery bypasses the duodenum (iron, calcium) and reduces intrinsic factor (B12). In a patient with new neuropathy or a stress fracture, ask about these exposures.
Which hormone is released by duodenal S cells in response to luminal acid and stimulates pancreatic bicarbonate secretion?
Cholecystokinin
Secretin
Motilin
Gastrin
After an ileocecal resection for Crohn disease, a patient develops macrocytic anemia and a sensory neuropathy of the feet. Which absorptive defect best explains these findings?
Loss of jejunal folate absorption
Loss of duodenal DMT1-mediated iron transport into enterocytes
Loss of gastric parietal cell acid secretion
Loss of terminal ileal B12-intrinsic factor absorption
Which three stimuli directly increase gastric parietal cell acid secretion, and where does a proton pump inhibitor act?
Secretin, somatostatin and prostaglandin E2; at the basolateral Na+/K+-ATPase
Norepinephrine, cortisol and insulin; at the carbonic anhydrase enzyme
CCK, GIP and motilin; at the apical chloride channel
Acetylcholine, gastrin and histamine; at the luminal H+/K+-ATPase
Sections you finish are checked off in the contents.