14.1 GI Physiology, Motility & Digestion

14.1 GI Physiology, Motility & Digestion

Quick Answer: Hormones (gastrin, CCK, secretin, GIP, motilin, somatostatin) coordinate acid, bile, enzymes, and motility. Parietal H+/K+-ATPase is the final common acid pathway. Enterokinase starts the trypsin cascade; bile salts recycle via the terminal ileum. Digestion finishes at the brush border; fat needs micelles and lymph. Motility = peristalsis + segmentation + MMC, driven by the enteric nervous system.

Gastrointestinal physiology on the CBSE is mechanism-first. Vignettes pair a hormone with a missing effect, a cell type with a product, or a gut segment with an absorption defect. Build a scaffold: control signals → secretory cells → enzyme and bile chemistry → absorption sites → motility patterns and enteric circuitry.

GI Hormones: Sources, Stimuli, and Effects

Gastrin is released from antral and duodenal G cells in response to amino acids/peptides, gastric distension, and vagal (GRP) input. It acts on parietal CCK2 (CCKB) receptors and ECL cells to raise acid, and it is trophic to gastric mucosa. Excess gastrin (Zollinger–Ellison) drives peptic ulceration and diarrhea from acid inactivation of enzymes and precipitation of bile salts.

Cholecystokinin (CCK) from duodenal/jejunal I cells responds to fatty acids and amino acids. Classic effects: gallbladder contraction, sphincter of Oddi relaxation, pancreatic acinar enzyme secretion, mild pyloric slowing of gastric emptying, and satiety signaling. Exam items often contrast CCK (enzymes + gallbladder) with secretin (bicarbonate).

Secretin from duodenal S cells is released by low duodenal pH. It stimulates ductal bicarbonate-rich pancreatic and biliary secretion, neutralizes chyme for optimal enzyme pH, and modestly inhibits gastrin and gastric acid. Without adequate bicarb, lipase and trypsin work poorly.

Gastric inhibitory peptide / glucose-dependent insulinotropic peptide (GIP) from K cells rises with oral glucose and fat. It potentiates insulin release (incretin effect) and historically was named for acid inhibition. Compare with GLP-1 (L cells)—also an incretin but more heavily tested in diabetes pharmacology.

Motilin from upper small-bowel M cells peaks in the interdigestive period and triggers migrating motor complex (MMC) phase III, the housekeeper wave that sweeps residual debris and bacteria toward the colon. Erythromycin is a motilin-receptor agonist used as a prokinetic.

Somatostatin from D cells (and enteric/pancreatic sources) is the general inhibitor: suppresses gastrin, acid, CCK, secretin, GIP, VIP, glucagon, insulin, and splanchnic blood flow. Octreotide mimics these actions clinically (variceal bleed, VIPoma, carcinoid symptoms).

Gastric Cell Types and Acid Regulation

The oxyntic (fundus/body) mucosa houses parietal cells (HCl + intrinsic factor), chief cells (pepsinogen), and ECL cells (histamine). Antral mucosa is richer in G and D cells. Mucous cells and surface epithelial cells secrete mucus and bicarbonate that form the unstirred gel barrier; prostaglandins (PGE2, PGI2) support mucus, bicarb, mucosal blood flow, and limit acid—NSAIDs injure by COX inhibition.

Parietal acid secretion uses basolateral uptake and apical H+/K+-ATPase (proton pump) insertion into canalicular membranes. Three physiologic stimulators converge:

1. Histamine (paracrine from ECL) → H2 receptors → cAMP
2. Acetylcholine (vagus / enteric) → M3 → Ca2+/IP3
3. Gastrin → CCK2 on parietal and (especially) ECL cells → Ca2+ and histamine release

Potentiation among pathways explains why H2 blockers reduce acid substantially and why PPIs (irreversible pump inhibitors) are most powerful. Inhibitors include somatostatin, prostaglandins, and enterogastrone signals when the duodenum is acidic or nutrient-rich. Intrinsic factor from parietal cells binds B12 for terminal-ileal absorption; autoimmune destruction of parietal cells causes pernicious anemia (see pathology section).

Pepsinogen from chief cells is cleaved to pepsin in acid pH; pepsin initiates protein digestion and is inactive when acid is neutralized distal to the pylorus.

Pancreatic Enzyme Activation Cascade

Acinar cells package zymogens: trypsinogen, chymotrypsinogen, proelastase, procarboxypeptidases, prophospholipase A2. Enterokinase (enteropeptidase) on duodenal brush border converts trypsinogen → trypsin. Trypsin then activates the remaining zymogens and can autoactivate more trypsinogen. Premature intraparenchymal activation (gallstone obstruction, alcohol, hypertriglyceridemia) is the core of acute pancreatitis pathophysiology.

Active enzymes: trypsin/chymotrypsin/elastase (endopeptidases), carboxypeptidases (exopeptidases), pancreatic amylase (starch), lipase + colipase (triglycerides), phospholipase A2, cholesterol esterase, nucleases. Ductal CFTR and secretin-driven HCO3− create alkaline juice; CFTR dysfunction thickens secretions and causes pancreatic insufficiency (CF).

Bile Salts and Enterohepatic Circulation

Hepatocytes conjugate primary bile acids (cholic, chenodeoxycholic) with glycine or taurine → bile salts, secreted with cholesterol and phospholipid into canaliculi, stored/concentrated in the gallbladder, and released under CCK. In the intestinal lumen, bile salts emulsify fat and form mixed micelles that ferry fatty acids, monoglycerides, fat-soluble vitamins (A, D, E, K), and cholesterol to the enterocyte brush border.

About 95% of bile salts are reabsorbed by apical sodium-dependent bile acid transporter (ASBT) in the terminal ileum, return via portal vein, and are resecreted by the liver—the enterohepatic circulation. Ileal resection or disease (Crohn) causes bile-salt deficiency, fat malabsorption, steatorrhea, and oxalate kidney stones (unabsorbed fatty acids bind Ca2+, freeing oxalate for colonic absorption). Bacterial deconjugation and 7α-dehydroxylation generate secondary bile acids; excess colonic bile salts cause secretory diarrhea.

Digestion and Absorption by Nutrient Class

Carbohydrates: Salivary and pancreatic amylases yield maltose, maltotriose, and limit dextrins. Brush-border lactase, sucrase, maltase, isomaltase (α-dextrinase) finish hydrolysis to monosaccharides. Glucose and galactose enter via SGLT1 (Na+-coupled); fructose via GLUT5; all exit basolaterally via GLUT2. Lactase deficiency → osmotic diarrhea and gas from bacterial fermentation.

Proteins: Gastric pepsin starts cleavage; pancreatic proteases dominate in the lumen; brush-border peptidases and cytoplasmic peptidases complete digestion. Amino acids use various Na+-dependent and independent transporters; di-/tripeptides use PEPT1 (H+-coupled)—clinically relevant for some drug absorption.

Fats: Emulsification → pancreatic lipase (needs colipase; inhibited if bile salts precipitate in extreme acid) → 2-monoglycerides + free fatty acids → micelles → diffusion into enterocytes → re-esterification to triglycerides → chylomicrons (require apoB-48; abetalipoproteinemia blocks this) → lacteals → thoracic duct. Medium-chain triglycerides can partly bypass micelle/chylomicron pathways and are used in bile-salt deficiency diets. Most fat absorption is jejunal; bile-salt reuptake is ileal.

Motility Patterns and the Enteric Nervous System

Peristalsis is aboral ring contraction behind a bolus with receptive relaxation ahead—propulsion. Segmentation is rhythmic standing contractions that mix chyme with enzymes and enhance mucosal contact. Gastric motility includes receptive relaxation (fundus), peristaltic grinding (antrum), and pyloric sieving; liquids empty faster than solids; fats and hypertonicity slow emptying via duodenal feedback (CCK and others).

Between meals, the MMC cycles every ~90 minutes: phase I quiescence, phase II irregular activity, phase III intense propulsive front (motilin-associated), phase IV transition. Failure of MMC (e.g., scleroderma, diabetic autonomic neuropathy, opioids) predisposes to small intestinal bacterial overgrowth.

The enteric nervous system (ENS) contains as many neurons as the spinal cord. Myenteric (Auerbach) plexus between circular and longitudinal muscle primarily controls motility. Submucosal (Meissner) plexus regulates secretion, absorption, and local blood flow. Intrinsic primary afferent neurons, interneurons, and motor neurons use ACh (excitatory), NO and VIP (inhibitory relaxation), serotonin, substance P, and other transmitters. Vagal parasympathetic input is excitatory overall to motility and secretion; sympathetic (norepinephrine) is inhibitory to motility and constricts splanchnic vessels. The gut can run basic programs without CNS input (hence transplanted bowel retains motility), but brain–gut pathways modulate pain, stress responses, and voluntary defecation.

High-yield clinical physiology links: vagotomy reduces acid and alters emptying; achalasia is failure of LES inhibitory (NO/VIP) neurons; Hirschsprung is congenital absence of ENS ganglia in distal bowel; VIP excess (VIPoma) causes secretory diarrhea and hypokalemia; opioids increase tone and decrease propulsive motility → constipation.

Master these control loops before pathology: every ulcer, malabsorption, and motility disease on CBSE is a broken version of a normal physiologic step.