Gastrointestinal Physiology - Digestive System (GIT, Accessory Organs)

The Digestive System: overview

• Gastrointestinal (GI) tract includes mouth, pharynx, esophagus, stomach, small intestine, and large intestine.
• Accessory digestive organs include teeth, tongue, salivary glands, liver, gallbladder, and pancreas.
• Primary functions: ingest, digest (mechanical + chemical), absorb nutrients, and defecate waste.
• Four basic processes (in order):
  • Ingestion: intake of food
  • Digestion: mechanical and chemical breakdown
  • Absorption: uptake of nutrients into blood/lymph
  • Defecation: elimination of feces

Key concepts: control of the GI tract

• Enteric Nervous System (ENS): intrinsic neural control
  • Myenteric (Auerbach) plexus regulates motility (frequency and strength of muscular contractions)
  • Submucosal (Meissner) plexus regulates mucosal secretions
• Autonomic Nervous System (ANS): extrinsic control
  • Parasympathetic (vagus) enhances GI secretion and motility
  • Sympathetic fibers generally inhibit GI activity
• Digestive regulation involves neural reflexes and hormones; phases can overlap and be simultaneous.

The Mouth and Salivary Glands

• Mouth functions: ingestion, taste and sensory responses, mastication, chemical digestion, swallowing, speech, respiration.
• Salivary glands (saliva production)
  • Minor glands: lingual, labial, palatine, buccal (small amounts)
  • Major glands: parotid, submandibular, sublingual
• Secretions by gland type
  • Parotid: watery saliva rich in amylase (serous cells)
  • Submandibular: mixed serous + mucus; amylase present but with mucus
  • Sublingual: mostly mucous; little amylase
• Saliva composition (rough outline)
  • Water ~97–99.5%; pH ~6.8–7.0
  • Mucus, ions (Na+, K+, Cl-, phosphate, bicarbonate)
  • Lysozyme (antibacterial), IgA (antibody), salivary amylase, lingual lipase
• Salivary digestion in the mouth
  • Mechanical: mastication reduces food to a bolus
  • Chemical: salivary amylase begins starch digestion; lingual lipase begins lipid digestion
• Important pH and buffering roles: bicarbonate and phosphate buffer acidic foods; Cl- activates salivary amylase

The Pharynx, Esophagus, and Deglutition (Swallowing)

• Pharynx: oropharynx & laryngopharynx propel food into the esophagus via coordinated muscular contractions.
• Esophagus: secretes mucus; transports food to stomach; lower esophageal sphincter (LES) prevents reflux.
• Swallowing stages (degultition)
  • Oral phase (voluntary): bolus moves from mouth to oropharynx
  • Pharyngeal phase (involuntary): bolus through pharynx to esophagus
  • Esophageal phase (involuntary): peristaltic propulsion into stomach; LES relaxes to allow entry
• Mechanism: peristalsis involves coordinated circular and longitudinal muscle contractions to push bolus downward.
• Note: a visual animation exists illustrating the pharyngeal and esophageal stages.

The Stomach

• Structure and volume
  • Empty volume ~50 mL; after a typical meal ~1–1.5 L; can reach up to ~4 L when extremely full
• Primary functions: reservoir for food, mechanical mixing, gastric juice secretion to form chyme
• Mechanical digestion (gastric motility)
  • Receptive relaxation: fundus accommodates arriving food
  • Peristalsis waves ~every 15–25 seconds; begin in body and intensify in antrum
  • Propulsion: move contents to the antrum
  • Retropulsion: larger particles are forced back toward the body for further mixing
  • Mixing cycles produce chyme (soupy/pasty semi-digested food)
  • Approximately ~3 mL of chyme are propelled into the duodenum with each mixing wave
• Chemical digestion (stomach secretions)
  • HCl production via carbonic anhydrase reaction; overall process includes enzyme activation and acidification
  • Major HCl formation step (simplified):
    CO2 + H2O
    ightleftharpoons H2CO3
    ightarrow HCO_3^- + H^+ ext{ (via CAH, with } H^+ ext{ pumped into lumen by H^+-K^+ ATPase})
  • Cl- is exchanged with bicarbonate; Cl- enters lumen and combines with H+ to form HCl
  • Alkaline tide: after stomach digestion, blood leaving the stomach has increased bicarbonate (alkaline) due to HCO3- accumulation
• Functions of HCl in the stomach
  • Activates pepsin and lingual lipase
  • Destroys ingested pathogens; aids iron reduction to Fe2+ for absorption
  • Converts Fe3+ to Fe2+ for hemoglobin synthesis
• Digestive enzymes and gastric juice components
  • Pepsinogen activated to pepsin by HCl; pepsin digests dietary proteins (roughly 10–15% of protein digestion occurs in the stomach)
  • Gastric lipase digests triglycerides to fatty acids and monoglycerides (roughly 10–15% of lipid digestion occurs in the stomach)
  • Carbohydrate digestion in stomach: amylase is inactivated by stomach acid; if starch is in an undigested state within a food mass it may be digested briefly in the stomach
• Cells and glands in gastric mucosa (gastric glands)
  • Mucous neck cells secrete mucus; surface mucous cells secrete mucus
  • Parietal (oxyntic) cells secrete HCl and intrinsic factor (IF)
  • Chief cells secrete pepsinogen and gastric lipase
  • G cells secrete gastrin (gastric endocrine hormone)
  • Enteroendocrine cells secrete various hormones (e.g., serotonin, histamine, somatostatin) and gut-brain peptides
• Intrinsic factor (IF)
  • Essential for absorption of vitamin B12 in the ileum; B12 is critical for red blood cell formation
  • Without IF, B12 absorption fails, leading to pernicious anemia; gastrectomy necessitates B12 supplementation
• Mechanisms limiting gastric injury and protection
  • Mucous coat, tight junctions between epithelial cells, rapid epithelial turnover (sloughing every 3–6 days)
  • Disruption can lead to peptic ulcers
• Gastric secretions—summary values
  • Gastric juice: about 2–3 L per day produced by gastric glands
  • Secretory cells include mucous neck cells, parietal cells, chief cells, G cells, and various enteroendocrine/gut-brain cells
• Stomach as a digestive chamber: primary roles in protein and fat digestion in early stages, with limited carbohydrate digestion due to acid inactivation of amylase

The Liver, Gallbladder, and Pancreas

• Overview
  • Liver processes chyme inputs from stomach and secretions from liver and pancreas into the duodenum near the stomach–small intestine junction
• The Liver: structure and basic organization
  • Largest gland (~1.4 kg)
  • Anatomic features include right/left lobes, caudate and quadrate lobes, falciform ligament, porta hepatis, hepatic artery proper, portal vein, bile duct
• Hepatic lobules
  • Functional units: hexagonal lobules with hepatocytes arranged around a central vein
  • Hepatic sinusoids: fenestrated capillaries allowing exchange between blood and hepatocytes; Kupffer cells (phagocytic) remove bacteria and debris
• Circulation in lobules
  • Hepatic portal triads contain: branch of hepatic portal vein (venous, nutrient-rich), branch of hepatic artery proper (arterial, oxygenated), and a bile ductule
  • Blood from the portal vein and hepatic artery mixes in sinusoids and flows to a central vein
• Major liver functions
  • Carbohydrate, lipid, and protein metabolism
  • Bile production, bilirubin excretion
  • Detoxification of drugs and hormones; processing of hormones
  • Phagocytosis (Kupffer cells)
  • Synthesis of plasma proteins (e.g., albumin, clotting factors)
  • Vitamin/mineral storage
• Bile: role and composition
  • Daily production: ~500–1000 mL
  • Bile is yellow-green, emulsifies fats, contains water, bile salts, cholesterol, bile pigments (bilirubin), phospholipids (lecithin), neutral fats, minerals
  • Bilirubin: derived from heme; bilirubin is conjugated and excreted into bile; gives stool its brown color (stercobilin) and urine its yellow color (urobilin)
  • Bile salts: formed from cholesterol; emulsify fats and aid micelle formation for lipid absorption; ~80% are reabsorbed in the ileum and returned to the liver via enterohepatic circulation; 20% excreted in feces; the liver synthesizes new bile acids to replace the pool daily
• Enterohepatic circulation of bile salts
  • Bile salts secreted into duodenum; reabsorbed in the ileum via Na+-bile salt cotransporter; returned to liver via portal blood; resecreted into bile
• The Gallbladder
  • Pear-shaped sac under the liver
  • Stores and concentrates bile by absorbing water/electrolytes; contracts to release bile into the duodenum when needed
• The Pancreas
  • Dual-role organ: endocrine (islets) and exocrine (acini)
  • Exocrine pancreatic juice: 1,200–1,500 mL/day; contains water, enzymes, zymogens, NaHCO3, and electrolytes; bicarbonate neutralizes stomach acid in the duodenum
  • Endocrine pancreas: pancreatic islets secrete insulin and glucagon
• Pancreatic enzymes (proteins digested by pancreatic juice)
  • Pancreatic amylase: digests starch
  • Proteases: trypsin, chymotrypsin, carboxypeptidase digest proteins (zymogens activated by enterokinase/trypsin)
  • Pancreatic lipase: digests fats
  • Nucleases: ribonuclease and deoxyribonuclease digest RNA/DNA
• Regulation of pancreatic secretion and bile
  • Cholecystokinin (CCK): secreted in response to amino acids and fatty acids in chyme; stimulates pancreatic enzyme secretion, bile/pancreatic juice discharge, gallbladder contraction, hepatopancreatic sphincter relaxation; contributes to satiety and slows gastric emptying
  • Secretin: secreted in response to acidic chyme; stimulates pancreatic bicarbonate secretion to neutralize chyme
  • Acetylcholine (ACh): parasympathetic; stimulates pancreatic enzyme secretion even before food arrives

The Small Intestine: Structure, Digestion, and Absorption

• Overview
  • Longest part of the GI tract; most digestion and absorption occur after chyme enters the small intestine
  • Regions: duodenum (chemical digestion by pancreatic enzymes), jejunum (major site of digestion and absorption), ileum
• The intestinal mucosa and villi
  • Villi: finger-like projections increasing surface area; core contains arterioles, capillaries, venules, and lacteals (lymphatics)
  • Epithelial cell types: absorptive cells, goblet cells, enteroendocrine cells, Paneth cells, microfolds (microvilli)
• The brush border and enzymes
  • Microvilli form the brush border; contains brush-border enzymes not released into lumen; responsible for final digestion steps and contact digestion
  • Carbohydrate-digesting brush-border enzymes:
  • α-dextrinase, maltase, sucrase, lactase
  • Protein-digesting brush-border enzymes: aminopeptidase, dipeptidase
  • Nucleotide-digesting enzymes: nucleosidases, phosphatases
  • Enterokinase (brush-border) activates trypsinogen to trypsin in the small intestine
• Intestinal secretions
  • 1–2 L of intestinal juice/day; pH ~7.4–7.8; mostly watery with mucus; enzymes largely in brush border and pancreatic juice
• Mechanical digestion: segmentation and migrating motor complex (MMC)
  • Segmentation: localized mixing contractions; frequency ~12/min in the duodenum and ~8–9/min in the ileum; purpose is to mix chyme with intestinal, bile, and pancreatic juices and expose contents to mucosa
  • Peristalsis (MMC): occurs after nutrients are largely absorbed; wave-like contractions starting in stomach region and moving distally; moves chyme toward the colon; chyme residence in small intestine ~3–5 hours
• Chemical digestion in the small intestine
  • Lipid digestion begins with emulsification by bile acids forming micelles; pancreatic lipase digests triglycerides into fatty acids and monoglycerides
  • Carbohydrates: pancreatic amylase continues starch digestion; brush-border enzymes complete digestion to monosaccharides (glucose, galactose, fructose)
  • Proteins: pancreatic proteases (trypsin, chymotrypsin, carboxypeptidase) break peptides; brush-border peptidases complete digestion to amino acids; amino acids/dipeptides/tripeptides absorbed
  • Nucleic acids: nucleases degrade DNA/RNA; nucleotidases/phosphatases yield nucleosides and bases absorbed
• Absorption in the small intestine
  • Forms absorbed into blood/lymph:
  • Monosaccharides: glucose, fructose, galactose
  • Amino acids, dipeptides, tripeptides
  • Fatty acids, glycerol, monoglycerides
  • Vitamins and electrolytes (Na+, K+, Cl-, Ca2+, etc.) and water
  • Transport mechanisms:
  • Glucose/galactose: secondary active transport with Na+ (SGLT)
  • Fructose: facilitated diffusion via GLUT5; glucose/galactose exit via GLUT2 into blood
  • Amino acids: Na+-dependent cotransport; some primary active transport
  • Dipeptides/tripeptides: PepT1 with H+; hydrolyzed to amino acids
  • Lipids: diffusion of fatty acids and monoglycerides into enterocytes; resynthesis into triglycerides; chylomicron formation; exocytosis into lacteals
  • Lipids and micelles
  • Bile salts aid emulsification and micelle formation, allowing lipid solubility and transport to enterocytes
  • Chylomicrons travel via lymphatic system (lacteals) to the thoracic duct, then into the bloodstream at the left subclavian vein junction
• Vitamins and minerals
  • Fat-soluble vitamins (A, D, E, K) absorbed with lipids; risk of poor absorption without fat intake
  • Water-soluble vitamins (B-complex, C) absorbed by diffusion; Vitamin B12 requires intrinsic factor for ileal absorption
• Relationship to liver and circulation
  • Absorbed monosaccharides and amino acids enter hepatic portal vein to the liver for processing; long-chain fatty acids enter the lymphatic system before entering the bloodstream

The Large Intestine (Colon)

• Primary roles
  • Receives ~500 mL of indigestible residue per day
  • Absorbs water and electrolytes; reduces residue to feces (~150 mL/day) via water reabsorption
  • Feces composition: ~75% water; remaining solids include bacteria, undigested fiber, fat, mucus, salts, and sloughed cells
• Mechanical digestion and motility
  • Gastroileal reflex accelerates ileal peristalsis after meals and relaxes the ileocecal valve
  • Haustral contractions occur every ~30 minutes; mass peristalsis occurs 1–3 times per day, triggered by gastrocolic and duodenocolic reflexes
• Chemical digestion by gut microbiome
  • ~800 bacterial species
  • Ferment remaining carbohydrates (cellulose, pectin) and proteins; synthesize vitamins B and K
  • Produces gases (flatus): ~500 mL/day; much is reabsorbed; byproducts include hydrogen sulfide, indole, skatole; odor from these compounds
• Summary
  • Absorption of remaining water and electrolytes; formation and excretion of feces

Regulation of Gastric Activity

• Integrated neural and hormonal control; three overlapping phases
  • Cephalic phase: brain senses sight/smell/taste/thought of food; vagus nerve stimulates gastric secretion via enteric nervous system; ~40% of stomach acid secretion occurs here; ACh stimulates pancreatic enzyme secretion
  • Gastric phase: food stretches the stomach; pH rises due to buffering by HCO3-; short and long neural reflexes (myenteric and vagovagal) enhance secretion and motility; hormonal signals amplify or modulate secretion
  • Intestinal phase: arrival of chyme in the duodenum slows gastric activity to allow digestion in the small intestine; intestinal gastrin briefly stimulates the stomach but secretin, CCK, and the enterogastric reflex inhibit gastric secretion and motility; sympathetic activity can suppress gastric function; vagal (parasympathetic) stimulation of the stomach is reduced
• Neural regulation
  • Short (myenteric) reflexes within the gut wall
  • Long (vagovagal) reflexes involving the brainstem (parasympathetic input)
• Hormonal regulation (key hormones and actions)
  • Secretin: released by duodenal/jejunal mucosa in response to acidic chyme; stimulates pancreatic bicarbonate secretion; inhibits gastric secretion
  • Cholecystokinin (CCK): released in response to amino acids and fatty acids in chyme; stimulates pancreatic enzyme secretion; causes gallbladder contraction and relaxation of hepatopancreatic sphincter; contributes to satiety and slows gastric emptying
  • Gastrin: produced by G cells; stimulates HCl secretion, pepsinogen secretion, and increases gastric motility; promotes contraction of the lower esophageal sphincter and facilitates gastric emptying by relaxing the pyloric sphincter
  • Other gut hormones: motilin, substance P, bombesin, vasoactive inhibitory peptide (VIP), gastrin-releasing peptide, somatostatin; overall roles in GI motility and secretion
• Practical implications
  • The coordinated actions prevent overload of the small intestine by regulating the rate of chyme entry and enabling optimal digestion and absorption

Key numerical and physical references (quick reference)

• Stomach: empty ~50 mL; after a meal ~1–1.5 L; max ~4 L
• Peristaltic wave interval: ~15–25 s
• Gastric emptying: ~3 mL of chyme moved into the duodenum with each wave
• Saliva: ~97–99.5% water; pH ~6.8–7
• Salivary components: mucus, Na+, K+, Cl-, phosphate, bicarbonate; lysozyme; IgA; salivary amylase; lingual lipase
• Pancreatic juice production: ~1,200–1,500 mL/day
• Bile production: ~500–1,000 mL/day
• Bile salts: ~80% reabsorbed in the ileum; ~20% excreted; enterohepatic circulation
• Large intestine transit time: ~36–48 hours for residue to become feces
• Gas production: ~500 mL/day (flatus)

Selected enzyme and transport highlights (summary)

• Carbohydrate digestion
  • Saliva: amylase begins starch digestion in the mouth (partial, in neutral pH)
  • Pancreatic amylase continues in the small intestine
  • Brush-border enzymes: α-dextrinase, maltase, sucrase, lactase; monosaccharides absorbed via SGLT (glucose/galactose with Na+), GLUT5 (fructose), GLUT2 (exit to blood)
• Protein digestion
  • Stomach: pepsinogen activated to pepsin; partial gastric protein digestion
  • Pancreas: trypsin, chymotrypsin, carboxypeptidase; proteolysis to peptides
  • Brush-border peptidases: aminopeptidase, dipeptidase; di-/tri-peptides absorbed with H+ via PepT1; free amino acids absorbed into blood
• Lipid digestion and absorption
  • Stomach: gastric lipase contributes modestly
  • Small intestine: bile salts emulsify fats; pancreatic lipase digests triglycerides to fatty acids and monoglycerides; micelles aid transport to enterocytes; reassembled into triglycerides and packaged into chylomicrons for lymphatic transport via lacteals
• Nucleic acids
  • Pancreatic nucleases digest RNA/DNA; brush-border nucleosidases/phosphatases generate nucleotides absorbed into blood

Quick connections to foundational principles

• The GI tract integrates neural (ENS, ANS) and hormonal signals to regulate secretion, motility, and digestion in a coordinated fashion.
• Absorption mechanics reflect transport physiology: secondary active transport (with Na+), facilitated diffusion, diffusion, and endocytosis-like processes for complex lipids via chylomicron formation.
• The liver–biliary system demonstrates enterohepatic circulation: efficient recycling of bile acids conserves lipids digestion efficiency.
• The microbiome of the large intestine contributes essential vitamins (B, K) and energy via fermentation, illustrating host-microbe symbiosis in human physiology.

Practical and clinical notes (summary implications)

• Vitamin B12 absorption requires intrinsic factor; deficiency leads to pernicious anemia; post-gastrectomy patients require B12 supplementation.
• Adequate fat intake is required for fat-soluble vitamin absorption (A, D, E, K).
• Peptic ulcers arise from disruption of protective gastric mucosal mechanisms (mucous coat, tight junctions, rapid epithelial turnover).
• Disruptions in enterohepatic circulation can affect lipid digestion and cholesterol homeostasis.
• Understanding gastric regulation phases helps explain symptoms like early satiety, bloating, and reflux in clinical scenarios.