8.3 Gastrointestinal Physiology

Ingestion and motility: enteric nervous system and slow waves

Gross GI anatomy and peritoneal relations are in 3.3 Digestive System. Physiology is what the enteric nervous system (ENS) does with that tube. The myenteric (Auerbach) plexus between circular and longitudinal muscle programs motility. The submucosal (Meissner) plexus programs secretion, absorption, and local blood flow. The ENS can run basic peristalsis without the CNS (a gut that has been denervated still shows local reflexes), but the vagus and pelvic parasympathetics supply the cranial and sacral parasympathetic drive, and sympathetic splanchnics generally inhibit motility and divert blood. Acetylcholine and substance P are excitatory to muscle; nitric oxide and VIP are the main inhibitory (relaxing) transmitters, essential for receptive relaxation and sphincter opening. Norepinephrine is inhibitory to the muscle and to enteric neurons.

Slow waves are oscillating resting potentials generated by interstitial cells of Cajal (ICC), the gut's pacemakers, electrically coupled to smooth muscle. Frequency is region-specific and is the ceiling on contraction rate: about 3/min in the stomach, 12/min in the duodenum, falling to about 8–9/min in the ileum, and slower and more variable in the colon. A slow wave that does not reach threshold produces no contraction. Spike potentials (Ca2+ action potentials) superimposed on the depolarized phase of a slow wave produce force. Hormones and nerves do not usually change slow-wave frequency; they change amplitude and the chance of spiking (and, in the stomach, can modulate the plateau). The esophagus and proximal stomach have more striated or tonic behavior; the orad stomach's receptive relaxation is vagal (NO/VIP) so a swallowed bolus does not spike fundus pressure.

Swallowing: oral (voluntary), pharyngeal (airway protected, UES relaxes), esophageal (primary peristalsis follows the swallow; secondary peristalsis clears residual). The lower esophageal sphincter (LES) is tonic ACh; swallow-induced relaxation is NO/VIP. Gastrin and acetylcholine raise LES tone; progesterone, ethanol, and a fatty meal lower it—relevant to reflux as mechanism, not as a Part II diagnosis drill.

Gastric motility: orad reservoir versus caudad antral mill that grinds solids against a closed pylorus until particles are ~1–2 mm. Liquids empty faster than solids; isotonic saline empties faster than hypertonic or acidic chyme. Fat and CCK are the strongest physiologic brakes on gastric emptying (enterogastric reflex plus hormone). Migrating myoelectric complexes (MMC) sweep the fasted gut about every 90–120 minutes; motilin is the hormone most tightly linked to phase III of the MMC—the housekeeper that clears residue and prevents bacterial overgrowth.

Small-intestine motility is segmentation (mixing, local ENS) and peristalsis (law of the intestine: oral contraction, anal relaxation). The ileocecal sphincter slows emptying into the colon; gastrin and a gastroileal reflex can open it after a meal. Colon: haustral mixing, mass movements often after meals (gastrocolic reflex, parasympathetic plus CCK/gastrin). Defecation: rectal stretch, intrinsic rectosphincteric reflex, internal sphincter relaxation (ENS, NO), external sphincter voluntary (pudendal). Spinal and pontine circuits coordinate; a sacral lesion removes the coordinated reflex.

Secretion: saliva, stomach, pancreas, and bile

Saliva is uniquely hypotonic among GI secretions because ductal epithelium reabsorbs NaCl (ENaC, Na/K-ATPase) faster than water can follow (low water permeability). Acini secrete plasma-like fluid with α-amylase (ptyalin), lingual lipase, mucin, lysozyme, lactoferrin, and IgA. Aldosterone increases ductal Na+ reabsorption and K+ secretion. Parasympathetic (CN VII, IX) drive is the main volume stimulus (IP3/Ca2+, also VIP vasodilates via kallikrein–bradykinin). Sympathetic β drive produces smaller, protein-rich saliva. Atropine dries the mouth; cystic fibrosis thickens secretions generally but salivary hypotonicity is a teaching contrast with pancreatic ducts, which use CFTR.

Gastric secretion: parietal cells secrete HCl and intrinsic factor. The pump is apical H+/K+-ATPase; Cl− follows; blood leaving the stomach during a meal is alkaline (alkaline tide). Stimuli potentiate one another: acetylcholine (M3), gastrin (CCK2 receptor), and histamine (H2) from ECL cells. Gastrin also acts by releasing ECL histamine. Somatostatin from antral D cells is the brake when luminal pH falls below ~3. Chief cells release pepsinogen (activated by acid to pepsin). Mucous neck cells and surface mucous cells plus PGE2 (mucus, HCO3−, mucosal blood flow) defend the epithelium; NSAIDs remove that prostaglandin shield. Phases: cephalic (vagus, thought/smell—atropine-sensitive), gastric (distention, peptides, gastrin), intestinal (initially gastrin from duodenal G cells, then enterogastrones inhibit).

Pancreas: acinar cells release zymogens packed with trypsin inhibitor. Duodenal enterokinase (enteropeptidase) activates trypsinogen → trypsin, which then activates the rest (chymotrypsinogen, procarboxypeptidase, proelastase, procolipase). Pancreatic α-amylase and lipase are secreted active. Ductal cells secrete HCO3−-rich fluid via CFTR and Cl−/HCO3− exchange, stimulated by secretin. CCK (plus vagal ACh) is the enzyme signal. CFTR failure thickens ductal secretions and maldigests fat.

Bile: hepatocytes secrete bile acids (cholic, chenodeoxycholic, conjugated to glycine or taurine), phosphatidylcholine, and cholesterol; ducts add HCO3− under secretin. Between meals the gallbladder concentrates bile (isosmotic NaCl absorption). CCK contracts the gallbladder and relaxes the sphincter of Oddi. In the lumen, bile salts form mixed micelles that ferry FA, MAG, cholesterol, and fat-soluble vitamins to the brush border. ~95% of bile salts are reabsorbed by ASBT in the terminal ileum and return via portal blood (enterohepatic circulation). Cholestyramine binds bile acids in the lumen and can lower cholesterol at the cost of fat-soluble-vitamin malabsorption.

Quick Answer: Slow waves are ICC pacemakers; spikes make force. CCK is fat/protein → enzymes and gallbladder. Secretin is acid → bicarbonate. Intrinsic factor is parietal; B12 and bile salts share the terminal ileum.

Digestion and absorption: carbohydrate, protein, fat, B12, bile salts

Carbohydrate: salivary and pancreatic amylase yield maltose, maltotriose, and α-limit dextrins; brush-border maltase, sucrase-isomaltase, lactase finish the job. Glucose and galactose enter on SGLT1 (Na+-coupled, secondary active—this is why oral rehydration with glucose plus salt works). Fructose uses GLUT5 (facilitated). All three exit basolaterally on GLUT2. Lactase deficiency leaves osmotic lactose for colonic bacteria (gas, osmotic diarrhea). There is no brush-border hydrolase for cellulose in humans.

Protein: pepsin starts the job but is not required (pancreatic proteases suffice). Trypsin, chymotrypsin, elastase, and carboxypeptidases produce oligopeptides and amino acids. Brush-border aminopeptidases and cytosolic peptidases finish. Absorption is both free amino acids (many Na+-coupled transporters, overlapping specificities) and di-/tripeptides via PEPT1 (H+-coupled)—the peptide path is quantitatively large. Neonates can take up some intact immunoglobulin by endocytosis; adults do not rely on that for nutrition.

Fat: mechanical emulsification plus bile salts increase surface area. Pancreatic lipase (with colipase, which lets lipase work at a bile-salt-coated interface) yields 2-monoglyceride and free fatty acids. Phospholipase A2 and cholesterol esterase contribute. Products enter mixed micelles, diffuse through the unstirred layer, and reform triglycerides in the enterocyte (smooth ER). Chylomicrons (apoB-48) exit to lacteals, not the portal vein—except medium-chain fatty acids, which can go portal unbound. Fat-soluble vitamins A, D, E, K ride the same micelle/chylomicron path. Without bile or lipase: steatorrhea, weight loss, and fat-soluble-vitamin deficits.

Vitamin B12 (cobalamin): dietary B12 binds salivary haptocorrin (R-protein) in acid; pancreatic proteases free it in the duodenum so it can bind intrinsic factor (IF) from parietal cells. The IF–B12 complex is taken up by cubilin/amnionless receptors on terminal-ileum enterocytes, then exported with transcobalamin II. Failure at parietal cells (autoimmune gastritis), pancreas (can't free B12 from haptocorrin), or terminal ileum (resection, Crohn disease) all cause deficiency; oral crystalline B12 can bypass IF only at pharmacologic doses.

Bile salts share that terminal ileum address (ASBT). Ileal resection therefore produces a double lesion: B12 malabsorption and bile-salt wasting. Spill of bile salts into the colon causes secretory diarrhea; depletion of the bile-salt pool causes fat malabsorption and oxalate kidney stones (unabsorbed fatty acids bind Ca2+, leaving oxalate free to be absorbed).

Other high-yield absorptive details: iron as Fe2+ via DMT1 in duodenum, exported by ferroportin, regulated by hepcidin; calcium via TRPV6 and calbindin, vitamin D–dependent in duodenum; Na+ via nutrient-coupled transporters, NHE3, and ENaC in distal colon (aldosterone); K+ largely paracellular, with colonic secretion under aldosterone. Water follows osmotically—the small bowel absorbs the bulk (liters per day of diet plus secretions); the colon mops up the remainder and determines stool liquidity.

Regulation: gastrin, CCK, secretin, somatostatin, and vagus

Gastrin (G cells, antrum and duodenum): stimuli are GRP (bombesin) from vagal postganglionics, luminal peptides/amino acids, and distention; acid and somatostatin inhibit. Actions: parietal acid, ECL histamine, mucosal growth, some increase in LES tone and antral motility. Gastrinoma (Zollinger–Ellison) is unregulated acid, ulcers, and inactivated pancreatic enzymes from a low duodenal pH.

CCK (I cells, duodenum/jejunum): stimuli are fatty acids and amino acids (not primarily acid or glucose). Actions: gallbladder contraction, Oddi relaxation, pancreatic enzyme secretion, slowed gastric emptying, a role in satiety. CCK works partly via vagal afferents (a true hormone and a paracrine/neural amplifier).

Secretin (S cells): stimulus is luminal acid (pH <4.5). Action: pancreatic and biliary HCO3− so enzymes meet a neutralized duodenum; also modest pepsinogen release and inhibition of further acid. Secretin is the bicarbonate hormone; CCK is the enzyme-and-bile hormone. They potentiate at the acinar/ductal unit.

Somatostatin (D cells, pancreas δ cells): universal inhibitor—gastrin, acid, CCK, secretin, VIP, glucagon, growth hormone. Released when the antrum is acid. GIP (K cells; glucose-dependent insulinotropic peptide) is released by oral glucose and augments insulin—the incretin effect (oral glucose beats IV glucose for insulin). Motilin times MMC phase III. VIP relaxes sphincters and stimulates intestinal secretion (VIPoma: secretory diarrhea). Histamine is the ECL paracrine for acid. Guanylin and bacterial enterotoxins raise cGMP/cAMP and open CFTR—secretory diarrhea as mechanism.

Vagus: cephalic phase of acid and pancreatic secretion, receptive relaxation, some CCK-mediated pancreatic enzyme release via vago-vagal loops. Atropine blocks the cholinergic limb but not every peptide limb. After truncal vagotomy, gastric emptying of solids is impaired unless a drainage procedure is added—anatomy from chapter 3 meeting motility here.