6.4 GI Motility, Secretion, Digestion & Absorption

GI Motility Patterns

The gastrointestinal (GI) tract uses several stereotyped motility patterns governed by enteric, parasympathetic, and sympathetic neural input and by GI hormones:

• Peristalsis — coordinated ring contractions behind a bolus and relaxation ahead of it, propelling contents distally. The law of the intestine describes this reflex mediated by enteric interneurons.
• Segmentation — alternating contraction and relaxation of adjacent segments, mixing contents with secretions and exposing them to absorptive mucosa without significant net forward movement. Predominant in the small intestine during feeding.
• Migrating Motor Complex (MMC) — cyclical peristaltic waves sweeping from stomach to ileum every ~90 minutes during fasting, clearing residual debris and bacteria ('housekeeper wave'). Motilin initiates MMC; erythromycin is a motilin agonist.
• Mass movements — large-amplitude colonic contractions propelling contents toward the rectum, often after meals (gastrocolic reflex).

Swallowing (Deglutition)

Swallowing has three phases:

1. Oral (voluntary) — tongue pushes the bolus into the pharynx.
2. Pharyngeal (involuntary) — the soft palate elevates to close the nasopharynx; the epiglottis covers the larynx; the upper esophageal sphincter (UES) relaxes; respiration briefly pauses. The swallowing center in the medulla coordinates this via cranial nerves V, VII, IX, X, XII.
3. Esophageal (involuntary) — primary peristalsis initiated by the swallowing center; secondary peristalsis triggered by local distention. The lower esophageal sphincter (LES) relaxes (via NO and VIP) to allow bolus entry into the stomach.

Defecation

The gastrocolic reflex after meals increases colonic mass movements. Fecal material stretches the rectum, triggering the defecation reflex — relaxation of the internal anal sphincter (smooth muscle, involuntary) and voluntary relaxation of the external anal sphincter (skeletal muscle, pudendal nerve). Contraction of the diaphragm and abdominal muscles increases intra-abdominal pressure.

GI Secretions

Salivary Secretion

Salivary glands (parotid, submandibular, sublingual) secrete α-amylase (initiates starch digestion), lingual lipase (initiates lipid digestion), mucus, lysozyme, and IgA. Parasympathetic (CN VII, IX) stimulation via muscarinic receptors produces a high-volume, watery secretion; sympathetic stimulation produces a low-volume, viscous secretion. Saliva is hypertonic when flow is slow and isotonic when flow is high due to ductal modification.

Gastric Secretion

The stomach secretes HCl, pepsinogen, intrinsic factor, mucus, and bicarbonate from distinct cell types in the gastric gland:

HCl secretion by parietal cells uses the H+/K+-ATPase (proton pump) on the apical membrane, with Cl- exiting through CFTR channels. Histamine (from ECL cells) acts on H2 receptors (Gs → cAMP); gastrin and ACh act via Ca2+ pathways. All three second messengers converge on the proton pump. Proton pump inhibitors (omeprazole) block H+/K+-ATPase irreversibly.

Gastric secretion has three regulatory phases:

1. Cephalic phase (~30%) — sight, smell, taste, and thought of food activate vagal nuclei; vagus stimulates parietal, chief, and ECL cells, and via GRP stimulates G cells.
2. Gastric phase (~60%) — gastric distention and peptides stimulate gastrin release and enteric reflexes; positive feedback (acid activates pepsinogen → pepsin → more peptides).
3. Intestinal phase (~10%) — duodenal chyme stimulates enteroendocrine cells; inhibitory feedback via secretin, GIP, CCK, and enterogastric reflex reduces gastric emptying.

Pancreatic Secretion

The exocrine pancreas secretes digestive enzymes and bicarbonate-rich fluid. Secretin (from S cells in response to duodenal acid) stimulates ductal centroacinar cells to release HCO3- (neutralizing acidic chyme). CCK (from I cells in response to duodenal fat and protein) stimulates acinar cells to release proenzymes: trypsinogen, chymotrypsinogen, procarboxypeptidases, proelastase, pancreatic lipase, colipase, pancreatic amylase, and phospholipase A2. Trypsinogen is activated to trypsin by duodenal enterokinase (enteropeptidase); trypsin then activates the other proenzymes.

Bile Secretion

Hepatocytes produce bile continuously; the gallbladder stores and concentrates it between meals. CCK stimulates gallbladder contraction and relaxation of the sphincter of Oddi. Bile salts (conjugated bile acids with glycine or taurine) are amphipathic molecules that emulsify dietary fats and form mixed micelles that deliver fatty acids and monoglycerides to the enterocyte apical membrane. Bile salts are reabsorbed in the terminal ileum (enterohepatic circulation, ~95% recirculated).

Digestion and Absorption

Carbohydrates

Starch is digested by salivary and pancreatic α-amylase into disaccharides (maltose, maltotriose, α-limit dextrins). Brush-border enzymes — maltase, sucrase, isomaltase (α-dextrinase), lactase — cleave these into monosaccharides:

• Glucose and galactose absorbed via SGLT1 (Na+-dependent cotransporter, apical), exit via GLUT2 (basolateral).
• Fructose absorbed via GLUT5 (apical), exits via GLUT2.

Lactase deficiency causes lactose intolerance (osmotic diarrhea, bloating).

Proteins

Gastric pepsin begins protein digestion; pancreatic proteases (trypsin, chymotrypsin, carboxypeptidases, elastase) cleave to oligopeptides and amino acids. Brush-border peptidases (aminopeptidases, dipeptidases) complete digestion. Amino acids are absorbed via Na+-dependent cotransporters (e.g., B0, b0,+); dipeptides and tripeptides via the PepT1 (H+-coupled) transporter. Output across the basolateral membrane via amino acid transporters.

Lipids

Lingual and gastric lipase initiate digestion. In the duodenum, pancreatic lipase (with colipase) cleaves triglycerides to free fatty acids (FFA) and 2-monoglycerides. Bile salts form micelles that ferry these products to the enterocyte, where they are re-esterified into triglycerides, packaged with apolipoproteins into chylomicrons, and secreted into lymph via lacteals. Medium-chain fatty acids (MCTs) bypass micelle formation and enter the portal blood directly.

Vitamins and Minerals

• Fat-soluble vitamins (A, D, E, K) — absorbed with micellar lipids; deficiencies in fat malabsorption.
• Vitamin B12 — gastric intrinsic factor binds B12; the complex is absorbed via cubilin receptors in the terminal ileum. Pernicious anemia results from loss of intrinsic factor (autoimmune parietal cell destruction).
• Iron — absorbed as Fe2+ in the duodenum via DMT1 (apical), exported via ferroportin (basolateral); ascorbic acid enhances absorption.
• Calcium — absorbed in the duodenum via TRPV6 (active, vitamin D–dependent) and paracellularly throughout the intestine.

Hormonal Regulation

The incretin effect describes GIP and GLP-1 amplifying insulin secretion in response to oral glucose compared with IV glucose. GLP-1 agonists (exenatide) and DPP-4 inhibitors (sitagliptin) exploit this mechanism for type 2 diabetes therapy.