Digestive System
The digestive system transforms consumed food into molecular nutrients absorbable by the body and safely expels indigestible residue as feces. It consists of the alimentary canal (mouth → anus) and accessory organs: liver (bile, nutrient processing), gallbladder (bile storage), pancreas (digestive enzymes + HCO₃⁻), and salivary glands. The enteric nervous system (~100 million neurons) provides semi-autonomous regulation of motility, secretion, and blood flow across every segment.
Overview
The digestive system coordinates mechanical, enzymatic, hormonal, neural, microbial, and immunological processes across a ~9-meter length of specialised epithelium. Three major dimensions define its physiology: mechanical (mastication, peristalsis, segmentation, defecation); chemical (salivary, gastric, pancreatic, and brush-border enzymes reduce macromolecules to monomers: starch → glucose, proteins → amino acids, triglycerides → fatty acids); and absorptive (the small intestinal villus-crypt epithelium absorbs ~8–9 litres of fluid per day along with all nutrients, vitamins, and minerals).
The enteric nervous system (ENS) — embedded in two plexuses within the gut wall and containing more neurons than the spinal cord — provides semi-autonomous regulation earning it the description "the second brain." Hirschsprung's disease (congenital absence of ENS ganglion cells in the distal colon → functional obstruction) illustrates that no other neural system can substitute for ENS function in the gut. The ENS communicates bidirectionally with the CNS via the gut-brain axis (vagal and spinal afferents), influencing mood, appetite, and stress responses; gut microbiome metabolites (short-chain fatty acids, tryptophan derivatives) modulate this axis.
The gut microbiome (~10¹³ bacteria in the colon, predominantly Firmicutes and Bacteroidetes) produces short-chain fatty acids (SCFA: butyrate, propionate, acetate), vitamin K₂, B vitamins, and secondary bile acids. It plays central roles in immune maturation (colonisation from birth drives Peyer's patch development and IgA production), metabolic regulation (butyrate is the primary colonocyte energy source), and protection against pathogen colonisation. Microbiome dysbiosis is implicated in IBD, obesity, type 2 diabetes, colorectal cancer, and anxiety/depression.
Anatomy & Structure — Segment by Segment
| Segment | Length / capacity | Key structures / cells | Primary function |
|---|---|---|---|
| Oral cavity | — | Teeth; salivary glands (parotid, submandibular, sublingual — ~1–1.5 L/day); tongue | Mastication; salivary amylase (starch → maltose); lingual lipase; antimicrobials (IgA, lysozyme, lactoferrin) |
| Esophagus | ~25 cm | Upper 1/3 striated → lower 2/3 smooth muscle; lower esophageal sphincter (LES) | Peristaltic propulsion; no digestion. LES prevents acid reflux — dysfunction → GERD → Barrett's metaplasia |
| Stomach | ~1 L capacity | Parietal cells (HCl via H⁺/K⁺-ATPase, intrinsic factor); chief cells (pepsinogen); G-cells (gastrin); D-cells (somatostatin); ECL cells (histamine) | Acid denaturation (pH 1.5–3.5); pepsin activation; bactericidal; gastric mixing and chyme formation; pyloric rate control → regulated nutrient delivery to duodenum |
| Duodenum | ~25 cm | I-cells (CCK); S-cells (secretin); ampulla of Vater; Brunner's glands (alkaline mucus) | CCK → pancreatic enzymes + bile; secretin → HCO₃⁻ neutralisation; iron (Fe²⁺, DMT1), Ca²⁺ (TRPV6), folate absorbed here |
| Jejunum | ~2.5 m | Tallest villi; SGLT1, GLUT5, PepT1; lacteals; fatty acid binding proteins (FABPs) | Primary absorption: glucose, amino acids, fatty acids, fat-soluble vitamins (A, D, E, K in micelles), most minerals |
| Ileum | ~3.5 m | Peyer's patches; terminal ileum: cubilin/amnionless receptor (B₁₂-IF complex); ASBT (SLC10A2 — bile salt reabsorption); ileocecal valve | B₁₂ absorption (terminal ileum only); ~95% bile salt recovery (enterohepatic circulation — 15–30 cycles/day) |
| Large intestine | ~1.5 m | Goblet cells (MUC2); colonocytes; taeniae coli; no villi; appendix (mucosa-associated lymphoid tissue) | Water/electrolyte reabsorption (~1.5 L/day → ~100 mL in feces); microbial fermentation → SCFAs; vitamin K₂ synthesis |
| Rectum / Anus | ~15–20 cm | Internal anal sphincter (smooth muscle, involuntary); external anal sphincter (skeletal, voluntary, pudendal nerve S2–S4) | Fecal storage; defecation reflex (rectoanal inhibitory reflex); voluntary defecation controlled by pontine micturition centre analogue |
Surface area amplification in the small intestine: plicae circulares/valves of Kerckring (×3) + villi (×10) + microvilli/brush border (×20) → total ×600 amplification → ~250 m² absorptive surface — approximately the size of a tennis court.
Function — Digestion, Absorption & GI Hormones
Carbohydrate Digestion
Salivary amylase (starch → maltose); pancreatic amylase → disaccharides/oligosaccharides; brush-border disaccharidases (maltase, sucrase-isomaltase, lactase) → glucose/fructose/galactose. Absorbed: SGLT1 (Na⁺-coupled active, glucose/galactose), GLUT5 (facilitated, fructose), GLUT2 (basolateral export). Lactase deficiency → lactose intolerance (~70% of adults worldwide).
Protein Digestion
Gastric pepsin (endopeptidase, active pH <4); pancreatic trypsin, chymotrypsin, elastase (activated by enteropeptidase/enterokinase cascade in duodenal brush border); brush-border peptidases → amino acids, di/tripeptides. Absorbed via PepT1 (di/tripeptides, H⁺-coupled), multiple specific Na⁺-coupled AA cotransporters (SLC6, SLC7 families).
Lipid Digestion
Lingual/gastric lipase (~30%); bile emulsification → mixed micelles (bile salts + monoglycerides + fatty acids); pancreatic lipase + colipase → fatty acids + monoglycerides → passive absorption → re-esterified in enterocyte ER → chylomicrons → secreted into lacteals → thoracic duct → left subclavian vein (bypasses liver first-pass). Medium-chain fatty acids (C6–C12) enter portal vein directly.
GI Hormones (Key)
Gastrin (G-cells, antrum): protein/distension → ↑HCl + ↑pepsinogen. CCK (I-cells, fat/protein): ↑pancreatic enzymes + ↑bile release + satiety. Secretin (S-cells, acid): ↑HCO₃⁻ + ↓gastric acid. GLP-1 (L-cells, all nutrients): strong incretin, ↓glucagon, satiety, ↓gastric emptying — semaglutide/liraglutide target. Motilin: migrating motor complex (MMC) every 90 min fasting. Somatostatin: broad inhibitory.
Pathology
Colorectal Cancer (CRC)
Second leading cause of cancer death globally (~935,000 deaths/year). Adenoma → carcinoma sequence: APC loss (Wnt/β-catenin → crypt hyperproliferation) → KRAS → TP53 → SMAD4 mutations over 10–15 years. Lynch syndrome (MMR mutations: MLH1, MSH2, MSH6, PMS2) → hereditary non-polyposis CRC (HNPCC); MSI-H tumours respond to anti-PD-1 (pembrolizumab). FAP: APC germline → thousands of polyps by age 20s, near-certain CRC without prophylactic colectomy. Screening: colonoscopy, FIT, stool DNA. Treatment: surgery ± FOLFOX; anti-VEGF (bevacizumab), anti-EGFR (cetuximab, panitumumab for RAS-wildtype mCRC).
Inflammatory Bowel Disease (IBD)
Crohn's disease: transmural, skip lesions, any GI segment (ileocolonic ~45%); granulomas, fistulae, strictures, abscesses; Th1/Th17-driven; NOD2 (CARD15) mutation highest single genetic risk factor (impairs Paneth cell antimicrobial function). Ulcerative colitis: mucosal only, continuous from rectum — Th2-driven; MUC2 deficiency + tight-junction dysfunction. Both: aminosalicylates (mesalazine), corticosteroids, immunomodulators (azathioprine, 6-MP), biologics (anti-TNF: infliximab/adalimumab; anti-IL-12/23: ustekinumab; anti-integrin: vedolizumab — gut-selective homing blockade). UC: dysplasia → CRC risk with duration and extent; surveillance colonoscopy.
Peptic Ulcer Disease and GERD
PUD: H. pylori (disrupts mucous barrier via urease + CagA/VacA virulence factors) — ~50% of global population infected, ulcers in ~10–15%. NSAIDs: COX-1 inhibition → ↓prostaglandins → ↓mucus/bicarbonate/mucosal blood flow. Complications: haemorrhage (most common), perforation, gastric outlet obstruction. Treatment: PPI + H. pylori eradication (triple or bismuth quadruple therapy; clarithromycin resistance rising → culture-guided where possible). GERD (~20% of Western adults): LES dysfunction → acid reflux → esophagitis → Barrett's esophagus (columnar metaplasia) → 0.5%/year risk of esophageal adenocarcinoma. Treatment: PPIs, lifestyle modification, anti-reflux surgery (Nissen fundoplication) for refractory cases.
Pancreatitis and Gallstone Disease
Acute pancreatitis: gallstones (~40%) + alcohol (~30%) are dominant causes; premature intrapancreatic zymogen activation → autodigestion → SIRS, multi-organ failure in severe necrotising pancreatitis (mortality 20–30%). Diagnosis: serum lipase >3× ULN; CT for severity. Chronic pancreatitis: fibro-inflammatory destruction → exocrine insufficiency (steatorrhoea, fat-soluble vitamin deficiencies) → endocrine insufficiency (type 3c diabetes). Main causes: alcohol, autoimmune (IgG4-related AIP), genetic (PRSS1, SPINK1, CFTR). Cholelithiasis (~15% of adults in developed countries): cholesterol stones (80%, bile supersaturation + impaired gallbladder motility) vs. pigment stones; complications: biliary colic, cholecystitis, choledocholithiasis, cholangitis, pancreatitis.
Celiac Disease and Malabsorption
Celiac disease: gliadin (wheat/rye/barley) + HLA-DQ2/DQ8 → adaptive immune attack on enterocytes → villous atrophy → malabsorption of fat, iron, calcium, B₁₂, fat-soluble vitamins. Anti-tTG IgA serology + duodenal biopsy. Treatment: lifelong strict gluten-free diet; refractory celiac → risk of T-cell lymphoma (EATL). Tropical sprue, Whipple's disease (Tropheryma whipplei), SIBO (small intestinal bacterial overgrowth — bloating, diarrhoea, B₁₂ deficiency; diagnosed by glucose/lactulose breath test; treated with rifaximin) complete the malabsorption differential.
Cross-Atlas Connections
References
- Hall JE. Guyton and Hall Textbook of Medical Physiology. 14th ed. Elsevier; 2021. Ch. 63-72. elsevier.com
- OpenStax. Anatomy & Physiology 2e, Ch. 23: The Digestive System. openstax.org
- Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN. CA Cancer J Clin. 2021;71(3):209-249. doi:10.3322/caac.21660 · PubMed 33538338
- Siegel RL, Wagle NS, Cercek A, Smith RA, Jemal A. Colorectal cancer statistics, 2023. CA Cancer J Clin. 2023;73(3):233-254. doi:10.3322/caac.21772 · PubMed 36856579
- World Health Organization. Global Hepatitis Report 2024. WHO; 2024. who.int