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Physiology of the Gastrointestinal Tract (GIT) - MBBS Level

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Overview

1. Movement of food (motility)
2. Secretion of digestive juices
3. Digestion (breakdown of food)
4. Absorption of nutrients, water, electrolytes, and vitamins
5. Control via local, nervous, and hormonal systems

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1. ANATOMY RELEVANT TO PHYSIOLOGY

Wall Layers (from outside in)

• The smooth muscle layers act as a syncytium - cells are connected via gap junctions, so action potentials travel freely throughout the muscle mass.
• Individual GI smooth muscle fibers are 200-500 µm long, 2-10 µm in diameter, arranged in bundles of up to 1000 parallel fibers.

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2. ELECTRICAL ACTIVITY OF GI SMOOTH MUSCLE

Resting Membrane Potential

• Resting membrane potential is -50 to -60 mV (less negative than skeletal muscle).
• Two types of electrical waves:
  1. Slow waves (basic electrical rhythm / BER)
  2. Spike potentials

Slow Waves

• Not action potentials - they are oscillating changes in membrane potential (+5 to +15 mV).
• Generated by interstitial cells of Cajal (ICC) - the pacemaker cells of the gut.
• Frequency varies by location:
  • Stomach: ~3/min
  • Duodenum: ~12/min
  • Ileum: ~8-9/min
• By themselves, slow waves do not cause contraction. They only cause contraction if spike potentials are superimposed on the slow wave crests.

Spike Potentials

• True action potentials, triggered when membrane potential rises above -40 mV.
• Caused by Ca²⁺ influx (not Na⁺ as in nerve/skeletal muscle).
• Appear on peaks of slow waves when the muscle is sufficiently stimulated.

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3. NEURAL CONTROL - THE ENTERIC NERVOUS SYSTEM (ENS)

Two Main Plexuses

Autonomic Control

• Parasympathetic (vagus nerve, CN X): increases overall GI activity - stimulates secretion and motility. Preganglionic fibers synapse on ENS neurons.
• Sympathetic: generally inhibits GI motility and secretion; causes vasoconstriction.

GI Reflexes

1. Local ENS reflexes - entirely within the gut wall
2. Prevertebral ganglion reflexes - e.g., enterogastric, colonoileal reflexes
3. Reflexes to/from CNS - defecation reflex, stomach relaxation on swallowing

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4. HORMONAL CONTROL - GUT HORMONES

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5. GIT MOTILITY

5a. Swallowing (Deglutition)

1. Voluntary phase: tongue pushes bolus into pharynx.
2. Pharyngeal phase (involuntary): soft palate closes nasopharynx, epiglottis closes larynx, upper esophageal sphincter relaxes, peristaltic wave initiated.
3. Esophageal phase: primary peristalsis carries bolus; secondary peristalsis clears any residue; lower esophageal sphincter (LES) relaxes to allow entry into stomach.

5b. Stomach Motility

1. Receptive relaxation - the fundus relaxes as food enters (mediated by the vagus nerve via VIP/NO) - allows 1.5 L without significant pressure rise.
2. Mixing - peristaltic waves in the body mix food with gastric juices to form chyme.
3. Emptying - the pyloric pump propels chyme into the duodenum.

• Gastric factors promoting emptying: volume/distension of stomach.
• Duodenal factors inhibiting emptying (enterogastric reflex):
  • Duodenal distension
  • Acid (pH <3.5-4)
  • Hyperosmolality of chyme
  • Fat and protein breakdown products
• CCK and GIP hormonally slow gastric emptying.

5c. Small Intestinal Motility

1. Segmentation contractions - the most common during eating. Circular muscle contracts rhythmically in alternating segments - this churns and mixes chyme with digestive juices. Does NOT move food forward.
2. Peristalsis - ring of contraction behind the bolus + relaxation ahead. Moves chyme toward ileocecal valve. Controlled by peristaltic reflex (myenteric plexus).

5d. Ileocecal Valve

• Acts as a one-way valve preventing backflow from colon to ileum.
• Normally contracted; relaxed by ileal peristalsis and gastroileal reflex.
• Cecal distension causes it to contract more tightly (ileocecal sphincter reflex).

5e. Large Intestinal Motility

1. Haustral shuttling: back-and-forth movement for water absorption.
2. Propulsive contractions: slow peristaltic waves moving contents toward rectum.
3. Mass movements: 1-3 times/day (especially after meals - gastrocolic reflex), propel large amounts of feces toward rectum.

• Filling of rectum triggers defecation reflex via afferents to sacral cord (S2-S4).
• Intrinsic reflex: Distension → myenteric plexus → relaxation of internal anal sphincter + strong sigmoid and rectal peristalsis.
• Spinal (parasympathetic) reflex: Amplifies intrinsic reflex via pelvic nerves.
• External anal sphincter is under voluntary (somatic) control via pudendal nerve.

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6. GIT SECRETION

6a. Salivary Secretion

• Ptyalin (salivary amylase): begins starch digestion; cleaves α-1,4 linkages.
• Mucin: lubrication.
• Lingual lipase: minor fat digestion.
• Lysozyme, IgA, lactoferrin: antibacterial protection.
• Bicarbonate: neutralizes acid, protects teeth.

6b. Gastric Secretion

• H⁺/K⁺-ATPase pump on luminal surface secretes H⁺ into the lumen in exchange for K⁺.
• Cl⁻ leaves via CFTR channels into lumen, combining with H⁺ to form HCl.
• CO₂ + H₂O → H₂CO₃ (catalyzed by carbonic anhydrase) → H⁺ + HCO₃⁻.
• HCO₃⁻ exits into blood in exchange for Cl⁻ (alkaline tide).
• Final lumen pH can reach 0.8 (very acidic).

1. ACh (vagus nerve) → muscarinic M₃ receptors
2. Gastrin → CCK-B receptors
3. Histamine → H₂ receptors → ↑ cAMP → activates H⁺/K⁺-ATPase

• Somatostatin, secretin, GIP, CCK (at high doses), prostaglandins E₂

• Tight junctions between epithelial cells prevent H⁺ back-diffusion.
• Mucous layer + HCO₃⁻ forms a pH gradient (pH 7 at cell surface, pH 2 in lumen).
• Prostaglandins maintain barrier by ↑ mucus/HCO₃⁻ and ↑ blood flow.
• NSAIDs break this barrier → peptic ulcers.

6c. Pancreatic Secretion

1. Aqueous/HCO₃⁻ component (from ductal cells): Neutralizes duodenal acid; enables enzyme activity.
2. Enzyme component (from acinar cells):

• Secretin (main stimulus for HCO₃⁻): released when pH <4.5 in duodenum.
• CCK (main stimulus for enzymes): released by fats and proteins in duodenum.
• Vagus nerve (ACh): stimulates both components, especially enzymes.
• Three phases: cephalic (~20%), gastric (~5-10%), intestinal (~70-75% - dominant).

6d. Bile Secretion

• Bile salts (primary: cholic acid, chenodeoxycholic acid; secondary: deoxycholic acid, lithocholic acid)
• Lecithin (phospholipids)
• Cholesterol
• Bilirubin (conjugated)
• Water, electrolytes, HCO₃⁻

1. Emulsification of fats: break large fat droplets into small ones, increasing surface area for lipase action.
2. Micelle formation: bile salts have a hydrophilic and hydrophobic end. They surround fatty acids and monoglycerides to form mixed micelles which carry lipids to the brush border for absorption.
3. Stimulate hepatic bile secretion (choleretic effect).
4. Activate lipase (in conjunction with colipase).

• Pre-hepatic (hemolytic): ↑ unconjugated bilirubin
• Hepatic (hepatocellular): ↑ both
• Post-hepatic (obstructive): ↑ conjugated bilirubin, pale stools, dark urine

6e. Intestinal Secretion

• Crypts of Lieberkühn in small intestine secrete ~1.8 L/day of isotonic fluid (mostly water and electrolytes) that carries enzymes to the brush border.
• Brush border enzymes: lactase, sucrase-isomaltase, maltase (disaccharidases); aminopeptidase, dipeptidase (peptidases); enterokinase.
• Goblet cells throughout intestine secrete protective mucus.
• Large intestine: mainly secretes mucus; absorbs water and electrolytes.

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7. DIGESTION AND ABSORPTION

7a. Carbohydrate Digestion and Absorption

1. Mouth: salivary amylase (ptyalin) → breaks starch to maltose, dextrins (brief action).
2. Stomach: amylase inactivated by HCl.
3. Duodenum: pancreatic amylase → starch to maltose, maltotriose, and limit dextrins.
4. Brush border: disaccharidases (maltase, sucrase, lactase) → monosaccharides (glucose, galactose, fructose).

• Glucose and galactose: active transport via SGLT-1 (Na⁺-glucose co-transporter) on brush border, then GLUT-2 on basolateral side into blood.
• Fructose: facilitated diffusion via GLUT-5 on brush border, then GLUT-2 basolateral.
• Enter portal blood → liver.

7b. Protein Digestion and Absorption

1. Stomach: pepsin (activated from pepsinogen at pH <5) → cleaves at aromatic amino acid residues; begins protein digestion (10-20%).
2. Duodenum: trypsin + chymotrypsin + elastase → polypeptides.
3. Carboxypeptidase (pancreatic): cleaves terminal amino acids from C-terminus.
4. Brush border peptidases (aminopeptidase, dipeptidase): final breakdown to amino acids and di/tripeptides.

• Free amino acids: absorbed via Na⁺-dependent co-transporters (similar to SGLT-1).
• Di- and tri-peptides: absorbed via PepT1 (H⁺-peptide co-transporter) - often more efficient than amino acid transporters.
• Both enter portal blood → liver.
• Small amounts of intact proteins absorbed by pinocytosis in neonates (allows passive immunity from colostrum).

7c. Fat Digestion and Absorption

1. Mouth: lingual lipase (minor).
2. Stomach: gastric lipase (minor), mechanical churning.
3. Duodenum:
   • Bile salts emulsify fat droplets.
   • Pancreatic lipase + colipase hydrolyze triglycerides → 2 free fatty acids + 1 monoglyceride.
   • Bile salts form mixed micelles with fatty acids and monoglycerides.
   • Micelles ferry lipids to the brush border.

• Lipid contents (fatty acids, monoglycerides, cholesterol, fat-soluble vitamins) diffuse passively from micelles into enterocytes.
• Inside enterocytes: fatty acids + monoglycerides → reassembled into triglycerides (in endoplasmic reticulum).
• Triglycerides packaged with apoprotein B-48, cholesterol, and phospholipids into chylomicrons.
• Chylomicrons exit via exocytosis into lymphatics (lacteals), not portal blood.
• Lymph → thoracic duct → left subclavian vein → systemic circulation.
• Short-chain fatty acids (SCFA) (< C12): water-soluble; absorbed directly into portal blood without chylomicron formation.

7d. Water and Electrolyte Absorption

• GI tract receives ~9 L/day (2 L ingested + 7 L secreted); absorbs ~8.9 L; only ~100-200 mL excreted in feces.
• Small intestine: absorbs the majority; water follows osmotic gradients created by active absorption of Na⁺, glucose, and amino acids.
• Colon: absorbs the final 1-1.5 L; crucial for concentrating stool.

• Jejunum: Na⁺/glucose and Na⁺/amino acid cotransport.
• Ileum: Na⁺/Cl⁻ exchange.
• Colon: aldosterone-sensitive electrogenic Na⁺ absorption (via ENaC channels) - this is where Na⁺ balance is fine-tuned.

7e. Vitamin Absorption

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8. GIT BLOOD FLOW (SPLANCHNIC CIRCULATION)

• Total splanchnic blood flow at rest: ~1400 mL/min (25-30% of cardiac output).
• Supplied by celiac, superior mesenteric, and inferior mesenteric arteries.
• Portal vein drains gut, pancreas, and spleen → liver.
• Mesenteric veins are large-volume, low-resistance reservoirs: in hemorrhagic shock, sympathetic vasoconstriction mobilizes 200-400 mL of blood to systemic circulation.
• Postprandial hyperemia: after eating, blood flow to intestines increases 3-4 fold (due to metabolic vasodilation, CCK, VIP, histamine, and reduced O₂).
• Autoregulation: Intestinal vessels autoregulate when perfusion pressure changes; local metabolites (CO₂, adenosine, K⁺) and myogenic reflexes maintain flow.

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9. GI MICROBIOTA

• The gut harbors trillions of microorganisms (the microbiota), mostly anaerobes; ~90% are Bacteroidetes and Firmicutes.
• Concentration increases along the gut: stomach/duodenum ~10¹⁻³/gram; colon ~10¹¹⁻¹²/gram.
• Established shortly after birth; influenced by delivery mode, breastfeeding, antibiotics.

1. Protection against pathogens (competitive exclusion).
2. Digestion: fermentation of undigested carbohydrates → SCFAs (butyrate, propionate, acetate) - main energy source for colonocytes.
3. Vitamin synthesis: K₂, biotin, folate, B₁₂ (small amounts).
4. Immune education: promotes mucosal IgA, regulatory T cells.
5. Metabolism: bile acid modification, drug metabolism.

• Dysbiosis (unhealthy microbiota) linked to IBD, obesity, metabolic syndrome, C. difficile infection.

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10. PHYSIOLOGY OF SPECIFIC GIT SEGMENTS - QUICK REVIEW

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11. MUCOSAL SURFACE AREA AMPLIFICATION

1. Plicae circulares (folds of Kerckring) - permanent folds of mucosa and submucosa; increase area 3x.
2. Villi - finger-like projections of mucosa; increase area 10x.
3. Microvilli (brush border) - on each enterocyte; increase area 20x.

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12. GIT PHYSIOLOGY OF DISORDERS (Key Clinical Correlations)

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Summary - The Big Picture

MOUTH
  ↓ (swallowing - medullary reflex)
ESOPHAGUS (peristalsis + LES relaxation)
  ↓
STOMACH (receptive relaxation → mixing → pyloric pump → chyme)
  ↓ (gastric emptying - regulated by enterogastric reflexes + CCK)
DUODENUM/JEJUNUM (neutralization by HCO₃⁻; enzyme digestion; hormone secretion)
  ↓
JEJUNUM/ILEUM (absorption of all nutrients, water, electrolytes, vitamins)
  ↓ (ileocecal valve)
COLON (water absorption, fermentation, fecal formation)
  ↓
RECTUM → DEFECATION REFLEX (S2-S4 + voluntary external sphincter control)

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• Slow waves and ICC (pacemaker cells)
• Phases of gastric secretion (cephalic 30%, gastric 60%, intestinal 10%)
• Mechanism of HCl secretion (H⁺/K⁺-ATPase, carbonic anhydrase, alkaline tide)
• Pancreatic enzyme activation (enterokinase activates trypsinogen)
• Chylomicron formation and lymphatic route for fat absorption
• SGLT-1 for glucose, GLUT-5 for fructose
• B₁₂ absorption in terminal ileum with intrinsic factor
• Enterohepatic circulation of bile salts
• GIT hormones: gastrin, secretin, CCK, GIP (their sources, stimuli, and actions)
• Defecation reflex (S2-S4 parasympathetic)