The Gastrointestinal System

Overview of the GI Tract

The gastrointestinal (GI) tract is a muscular tube extending from the mouth to the anus, supported by accessory organs — salivary glands, pancreas, liver, and gallbladder. Its primary functions are motility (moving luminal contents), secretion (enzymes, acid, mucus, bile), digestion (chemical breakdown of macromolecules), and absorption (transfer of nutrients into the bloodstream). A complex enteric nervous system (ENS), sometimes called the "second brain," coordinates these processes with input from the autonomic nervous system and endocrine cells.

GI Motility

Motility is generated by smooth muscle in the muscularis externa, arranged in inner circular and outer longitudinal layers. The basic electrical rhythm (slow waves) is set by interstitial cells of Cajal (ICCs), which act as pacemakers. Action potentials are superimposed on slow waves when contractile threshold is exceeded.

Peristalsis: a wave of circular muscle contraction behind and relaxation ahead of the bolus. Co-ordinated by the ENS via ascending excitation (ACh) and descending inhibition (NO, VIP).

Segmentation: rhythmic, non-propulsive contractions that churn and mix intestinal contents with digestive secretions, maximising contact with the absorptive mucosa.

Migrating motor complex (MMC): inter-digestive motility pattern (every 90–120 min during fasting), "housekeeping" sweeping of residue into the colon. Phase III involves powerful peristaltic waves originating in the stomach. Triggered by motilin.

Gastric Acid Secretion

Parietal cells in the gastric body secrete HCl via H⁺/K⁺-ATPase (proton pump). Regulation is by three parallel pathways: (1) neural (ACh via M₃ receptors — directly stimulates proton pump and indirectly via ECL cells); (2) endocrine (gastrin from G cells of the antrum — stimulates ECL cells to release histamine); (3) paracrine (histamine from ECL cells acts on H₂ receptors on parietal cells, the dominant stimulatory pathway). Somatostatin from D cells inhibits all three pathways. Proton pump inhibitors (PPIs, e.g., omeprazole) irreversibly block H⁺/K⁺-ATPase. H₂ blockers (e.g., ranitidine) competitively block histamine H₂ receptors.

Chief cells secrete pepsinogen, activated to pepsin by HCl (pH <2). Mucus neck cells secrete mucus and HCO₃⁻ (prostaglandin-mediated), forming a protective gel layer.

Pancreatic Secretion

The exocrine pancreas secretes ~1.5 L/day of juice rich in digestive enzymes and HCO₃⁻. Acinar cells produce zymogens (trypsinogen, chymotrypsinogen, proelastase, prolipase, prophospholipase) activated in the duodenal lumen when enteropeptidase cleaves trypsinogen to trypsin (trypsin then activates the other zymogens). Ductal cells secrete HCO₃⁻-rich fluid (regulated by secretin from S cells of the duodenum in response to luminal acid) to neutralise gastric acid.

CCK (cholecystokinin), released by I cells of the duodenum in response to fats and protein, stimulates acinar cell secretion and gallbladder contraction.

Bile and Fat Digestion

Hepatocytes continuously produce bile (~600–800 mL/day), consisting of bile salts (conjugated bile acids — cholic and chenodeoxycholic acids conjugated to glycine or taurine), cholesterol, phospholipids, bilirubin, and electrolytes. Bile is stored in the gallbladder (concentrated ~10-fold) and released into the duodenum in response to CCK. Bile salts emulsify dietary fat (increasing surface area) and form mixed micelles with fatty acids, monoglycerides, and fat-soluble vitamins (A, D, E, K), enabling their absorption by enterocytes. Bile salts undergo enterohepatic circulation — reabsorbed in the terminal ileum and returned to the liver via the portal vein.

Absorption of Nutrients

Carbohydrates: digested to monosaccharides by salivary and pancreatic amylase (polysaccharides) and brush-border enzymes (maltase, sucrase, lactase). Glucose and galactose are absorbed by SGLT1 (Na⁺-coupled); fructose via GLUT5 (facilitated diffusion).

Proteins: digested by pepsin (stomach), trypsin/chymotrypsin/elastase (pancreas), and carboxypeptidases. Absorbed as amino acids and di/tripeptides (via PepT1).

Fats: triglycerides emulsified by bile salts, hydrolysed by pancreatic lipase. Fatty acids and monoglycerides absorbed passively into enterocytes, re-esterified, packaged as chylomicrons, and exported via lacteals into lymph.

Fat-soluble vitamins (A, D, E, K): absorbed with fats in micelles. Vitamin B₁₂: requires intrinsic factor (from gastric parietal cells) for absorption in the terminal ileum.

The Gut-Brain Axis

The ENS contains ~500 million neurons organised into the submucosal plexus (Meissner's — controls secretion and blood flow) and myenteric plexus (Auerbach's — controls motility). Key neurotransmitters: ACh (excitatory), NO and VIP (inhibitory). Gut hormones including GLP-1, GIP, PYY, and ghrelin signal to the hypothalamus to regulate appetite and energy balance. The vagus nerve carries ~80% afferent (gut-to-brain) fibres, transmitting satiety signals.