The human digestive system accomplishes the transformation of complex macromolecules — polysaccharides, proteins, triglycerides, and nucleic acids — into absorbable monomers through a tightly coordinated sequence of mechanical and chemical events along the alimentary canal. This canal spans from the mouth to the anus and constitutes a continuous tube through which food progresses via peristaltic movement coordinated by the enteric nervous system.
Oral Phase: Digestion commences in the mouth, where masticatory forces from the teeth mechanically reduce food into smaller particles, vastly increasing the surface area available for enzymatic action. Simultaneously, the three pairs of salivary glands — the parotid (largest), sublingual, and submandibular glands — secrete saliva containing salivary amylase (ptyalin). This enzyme initiates carbohydrate digestion by hydrolysing starch to maltose, isomaltose, and limit dextrins at its optimal pH of 6.8. The lubricated, chewed mass (bolus) is swallowed and propelled via peristalsis through the pharynx and oesophagus into the stomach.
Gastric Phase: The stomach is a J-shaped muscular organ whose interior mucosal surface is thrown into longitudinal folds called rugae, permitting substantial expansion as food accumulates. Gastric glands within the stomach wall contain specialized cell populations: parietal (oxyntic) cells secrete hydrochloric acid (HCl), while chief (zymogenic) cells secrete pepsinogen. HCl performs three critical roles — it creates the highly acidic environment (pH 1.5–2.0), which activates pepsinogen to active pepsin, provides the optimal pH for pepsin's proteolytic action, and destroys most ingested pathogens. Pepsin cleaves proteins into large peptide fragments. A thin layer of alkaline mucus secreted by goblet cells protects the stomach wall from self-digestion. Chief cells also secrete gastric lipase, which acts on short-chain triglycerides at pH 4.0–5.0. Gastric churning homogenises food with secretions into chyme, the semi-fluid, acidic mass that is released through the pyloric sphincter in regulated boluses into the duodenum. The hormone gastrin, secreted by G-cells of the pyloric stomach in response to food (especially proteins), amplifies this gastric phase by stimulating both HCl and pepsinogen secretion.
Small Intestinal Phase — Digestion: The duodenum receives two pivotal secretions. Pancreatic juice, delivered via the pancreatic duct, contains an enzyme suite: the proenzymes trypsinogen, chymotrypsinogen, proelastase, and procarboxypeptidase are activated by enterokinase — an enzyme secreted by the duodenal mucosa, not the pancreas — which converts trypsinogen to trypsin. Trypsin then autocatalytically activates more trypsinogen and cascades to activate chymotrypsinogen (→ chymotrypsin), proelastase (→ elastase), and procarboxypeptidase (→ carboxypeptidase). Pancreatic juice also contains active enzymes: lipase, amylase (which continues starch and begins glycogen digestion at pH 7.0–8.0), and nucleases (DNase and RNase). Bile, produced by the liver and stored (concentrated) in the gallbladder, is released into the duodenum by cholecystokinin-driven gallbladder contraction. Bile contains bile salts that physically emulsify fat globules into smaller droplets, dramatically increasing the surface area available for pancreatic lipase — critically, bile performs only emulsification and contains no digestive enzymes whatsoever. The acidic chyme is neutralized by bicarbonate-rich pancreatic juice secreted in response to secretin (released by S-cells on detecting acidic chyme in the duodenum), raising the luminal pH to ~7–8, optimal for pancreatic enzymes.
In the jejunum and ileum, the intestinal mucosa is specialized for absorption by fingerlike projections called villi, each covered by enterocytes bearing microvilli (the brush border), together amplifying absorptive surface area approximately 600-fold. Membrane-bound brush border enzymes complete digestion at the absorption surface: maltase converts maltose to two glucose molecules; sucrase converts sucrose to glucose and fructose; lactase converts lactose to glucose and galactose; aminopeptidase and dipeptidases cleave peptides from the N-terminal end and dipeptides, respectively, to amino acids; nucleotidases and nucleosidases reduce nucleotides to nucleosides and then to nitrogenous bases plus pentose sugars.
Absorption: Glucose and amino acids are absorbed by secondary active transport (sodium-glucose co-transporters, SGLT; sodium-amino acid co-transporters) into blood capillaries within each villus. These capillaries drain into the portal vein, delivering absorbed nutrients to the liver for processing. Fatty acids and monoglycerides enter enterocytes by passive diffusion and are re-esterified into triglycerides, packaged with cholesterol, phospholipids, and apolipoprotein B48 into chylomicrons, then exported by exocytosis into lacteals — lymphatic capillaries in each villus core. Chylomicrons travel through mesenteric lymphatics to the thoracic duct, emptying into the left subclavian vein and entering systemic circulation, bypassing the liver. Fat-soluble vitamins (A, D, E, K) follow this same route.
Large Intestinal Phase: The large intestine, characterised by haustra (sacculations), receives the largely nutrient-depleted residue. Its primary function is water reabsorption (~1.3–1.8 L daily) by osmosis, along with mineral absorption. Symbiotic bacteria colonising the colon synthesize vitamins B and K. The compacted, dehydrated residue (faeces) is stored in the rectum and expelled through the anus via the defecation reflex.
Hormonal Coordination: Four gut hormones orchestrate this process. Gastrin (G-cells, pyloric stomach, triggered by food) stimulates HCl and pepsinogen. Secretin (S-cells, duodenum, triggered by acidic chyme) stimulates pancreatic bicarbonate. CCK (I-cells, duodenum, triggered by fats and amino acids) simultaneously triggers gallbladder contraction (bile release) and pancreatic enzyme secretion. GIP (K-cells, duodenum, triggered by fats and glucose) inhibits gastric acid and stimulates insulin release (incretin effect), coordinating the body's glucose-handling response.
The most tested NEET concept in this chapter is that bile contains no digestive enzymes — it only emulsifies fats — and that enterokinase, which initiates the pancreatic proenzyme cascade, is a duodenal (intestinal), not pancreatic, enzyme.