Gastrointestinal System

The role of the gastrointestinal system is to break down food mechanically and enzymatically into molecules that can be absorbed into the blood and taken to the liver to be used for synthesis.

  • The epithelium in the GI tract has several functions:

    • Protective - oral cavity and pharynx, oesophagus, anal canal etc.

    • Secretory - stomach: columnar cells arranged as glands for acid secretions.

    • Absorptive - small intestine, villi and glands, linked by enterocytes specialised for absorption by microvilli. Goblet cells produce mucus for lubrication and protection.

  • The basic template of the GI tube is the same throughout.

    • Inner Lining - Mucosa

      • Consists of an epithelium, basement membrane, laminal propria and muscularis mucosa (folded lining).

    • Support - Submucosa

      • Consists of connective tissue, blood vessels, lymphatics and nerves. Contains submucosal plexus which supplies glands.

    • Muscle - Muscularis Externa/Propria

      • Consists of smooth muscle responsible for peristalsis and is modulated by the autonomic nervous system (myenteric plexus modulates peristalsis).

    • Outer Wrapping - Adventitia/Serosa

      • Contains a serous membrane - squamous epithelial cells secrete a small amount of fluid to allow organs to glide over each other.

  • Sphincters are thickenings of smooth muscle.

    • Oesophageogastric - prevents reflux of stomach content.

    • Pyloric - between stomach and duodenum, controlling release of food.

    • Ileocaecal - between small and large intestine.

    • Internal Anal - upper anal canal - retains faeces.

  • Gut Associated Lymphoid Tissue

    • Ranges from individual T lymphocytes and macrophages to large aggregates composed of T and B lymphocytes.

Gastrointestinal System Organs

  • Mouth

    • Digestion between with mastication (chewing), with saliva secreted which contains amylase for digestion of starch and glycogen.

  • Salivary Glands

    • Serous secretion of amylase.

    • Secretion of mucous, which contains mucins.

  • The Swallowing Reflex

    • The tongue pushes bolus against the soft palate and back of mouth, triggering the reflex.

    • Upper oesophageal sphincter relaxes while epiglottis closes to keep swallowed material out of the airways.

    • Food moves downwards into the oesophagus, propelled by peristalsis.

  • Oesophagus

    • Conduction: acts as a conduit for swallowed food and fluids, moving them from mouth to stomach.

    • Peristalsis: coordinated, wave-like contractions of circular and longitudinal muscles propel the bolus downward.

  • Stomach

    • Luminal surface composed entirely of columnar epithelial mucous cells.

      • This protects the mucosa from acid attack, and secretes bicarbonate ions to lower local pH.

    • The acidic environment of the stomach is stimulated by gastrin, ACh and histamine. The overall pH is around 1.0-3.5.

    • Lined with folds called rugae, increasing surface area and enabling maximal contract between stomach contents and gastric mucosa.

    • Has an oblique layer to facilitate churning.

    • Releases food into small intestine via the pyloric sphincter.

  • Gastric Pits and Glands

    • Parietal (oxyntic) cells produce HCl and absorb vitamin B12.

    • Chief (peptic or zymogenic) cells produce enzymes such as pepsinogen.

    • Enteroendocrine cells produce hormones, such as gastrin, serotonin, vasoactive intestinal peptide (VIP) and somatostatin.

  • Pancreatic Acini

    • Acini are clusters of secretory cells that surround ducts.

      • They produce digestive enzymes, such as proteases, amylases and lipases.

      • They are packaged in zymogen granules and are inactive to prevent autodigestion.

      • Duct epithelial cells secrete bicarbonate ions to control pH in direct relation the amount of HCl produced in the stomach.

  • Biliary System

    • Consists of the ducts from the liver to the duodenum and the gallbladder.

      • Duodenal release of cholecystokinin (CCK) stimulates contraction of the gallbladder and relaxation of the sphincter of Oddi so secretions can enter the small intestine.

    • The common bile duct transports bile from the liver and/or gallbladder to the duodenum.

      • It joins with the pancreatic duct to form Ampulla of Vater

        • Regulates flow from the pancreas and gallbladder to duodenum.

    • The gallbladder concentrates bile, and stores around 50mL.

      • It is synthesised in the hepatocytes and is secreted into the canaliculi.

  • Liver

    • Synthesises bile, and secretes it for digestion of fat.

    • Excretes bilirubin (breakdown product of haem).

    • Protein metabolism.

    • Carbohydrate metabolism.

    • Lipid metabolism.

    • Detoxification.

Digestion and Absorption of Carbohydrates:

  • Carbohydrates in the diet are mainly polysaccharides (e.g. starch), disaccharides (e.g. lactose, sucrose), and small amounts of monosaccharides (e.g. glucose, fructose). Digestion breaks complex carbs into monosaccharides, which are then absorbed into the bloodstream.

Digestion:

  • Mouth (Oral Cavity)

    • Salivary amylase begins digestion by breaking starch into maltose and dextrins.

    • Limited action due to short exposure and inactivation by stomach acid.

  • Stomach

    • No significant carbohydrate digestion (acid denatures salivary amylase).

  • Small Intestine (Major Site)

    • Pancreatic amylase continues starch digestion into disaccharides (maltose) and oligosaccharides

    • Brush border enzymes on the surface of enterocytes complete digestion:

      • Maltase: maltose → 2 glucose

      • Lactase: lactose → glucose + galactose

      • Sucrase: sucrose → glucose + fructose

      • Isomaltase: α-limit dextrins → glucose

Absorption:

  • Glucose and Galactose:

    • Absorbed via SGLT-1 (sodium-glucose cotransporter) – secondary active transport

    • Requires Na⁺ gradient maintained by Na⁺/K⁺ ATPase

  • Fructose:

    • Absorbed via GLUT-5 – facilitated diffusion

  • All monosaccharides exit enterocytes into the blood via GLUT-2 on the basolateral membrane

Example - Digestion and Absorption of Maltose:

  • Maltase breaks maltose into two glucose molecules, absorbed by the enterocytes (intestinal epithelial cells).

  • Glucose is transported into these cells via SGLT1 (Sodium-Glucose Linked Transporter 1), “active transport” mechanism that requires sodium (Na⁺) ions.

  • This process relies on the sodium concentration gradient maintained by the Na⁺/K⁺ ATPase pump, which actively pumps sodium out of the cell into the bloodstream.

  • Once inside the enterocytes, glucose exits into the bloodstream through, a facilitated diffusion transporter that moves glucose down its concentration gradient into the capillaries of the intestinal villi.

Digestion and Absorption of Proteins:

  • Dietary proteins must be broken down into amino acids, dipeptides, and tripeptides to be absorbed. Digestion involves gastric, pancreatic, and intestinal enzymes, with absorption occurring in the small intestine.

Digestion:

  • Stomach

    • Chief cells secrete pepsinogen (inactive zymogen)

    • Acid (HCl) from parietal cells lowers pH → activates pepsinogen to pepsin

    • Pepsin: an endopeptidase that begins protein digestion by cleaving peptide bonds, especially after aromatic amino acids (e.g. phenylalanine, tryptophan)

  • Small Intestine (Duodenum & Jejunum)

    • Pancreatic enzymes are secreted as inactive zymogens and activated in the intestine:

      • Trypsinogen → Trypsin (activated by enterokinase from intestinal brush border)

      • Trypsin then activates:

        • Chymotrypsinogen → Chymotrypsin

        • Proelastase → Elastase

        • Procarboxypeptidases A & B → Carboxypeptidases

    • These enzymes digest proteins into oligopeptides and free amino acids

  • Brush Border Enzymes

    • Peptidases on enterocyte surfaces further break down peptides to amino acids, dipeptides, and tripeptides.

Absorption:

  • Amino acids: absorbed via Na⁺-dependent co-transporters (active transport).

  • Dipeptides and tripeptides: absorbed by H⁺-dependent co-transporters (PEPT1) and hydrolysed into amino acids within enterocytes.

  • Amino acids exit enterocytes into the bloodstream via facilitated diffusion.

Digestion and Absorption of Lipids:

  • Dietary lipids (mainly triglycerides, along with cholesterol, phospholipids, and fat-soluble vitamins) are hydrophobic and require emulsification and enzymatic breakdown for absorption. Digestion occurs mainly in the small intestine.

Digestion:

  • Mouth & Stomach (Minor Contribution)

    • Lingual lipase (from salivary glands) and gastric lipase begin digestion of triglycerides into fatty acids and diglycerides

  • Small Intestine (Major Site)

    • Emulsification:

      • Bile salts (from liver, stored in gallbladder) are secreted into the duodenum

      • They emulsify fat globules into micelles, increasing surface area for enzymes

      • Emulsification is essential for efficient lipase action

  • Enzymatic digestion:

    • Pancreatic lipase (with co-lipase) hydrolyses triglycerides → 2 free fatty acids + 1 monoglyceride

    • Cholesterol esterase and phospholipase A₂ digest cholesterol esters and phospholipids.

Absorption:

  • Micelle Formation

    • Micelles are water-soluble aggregates of bile salts, free fatty acids, monoglycerides, cholesterol, and fat-soluble vitamins

    • They ferry lipids to the brush border of enterocytes

  • Uptake by Enterocytes

    • Lipid components diffuse across the apical membrane of enterocytes

    • Inside the enterocyte:

      • Fatty acids and monoglycerides are re-esterified into triglycerides

      • Packaged with cholesterol, phospholipids, and apolipoproteins into chylomicrons.

  • Transport

    • Chylomicrons are exocytosed into lacteals (lymphatic capillaries) → enter the thoracic duct → systemic circulation

    • Short- and medium-chain fatty acids are absorbed directly into the portal blood.

Absorption of Iron:

  • Transferrin is secreted by enterocytes, which bind to iron.

    • The transferrin-iron complex binds to a receptor, where it is taken into the cell by receptor-mediated endocytosis,

      • Some iron is stored in the enterocyte as ferritin.

Feeding-Fasting Cycle:

  • The feeding-fasting cycle is regulated by complex interactions between satiety signals, neural pathways, and gastrointestinal secretions to maintain energy balance and efficient digestion.

Satiety Signalling and Regulation of Food Intake:

  • Satiety signals arise from:

    • Gut hormones (e.g., cholecystokinin [CCK], peptide YY, GLP-1) released in response to nutrients

    • Mechanical stretch of the stomach wall activating vagal afferents

    • Nutrient levels in the blood (glucose, fatty acids)

  • These signals are integrated in the hypothalamus (especially the arcuate nucleus), which regulates hunger and satiety via:

    • Orexigenic neurons (stimulate appetite)

    • Anorexigenic neurons (suppress appetite)

  • Neural pathways: Vagal afferents from the GI tract convey information to the brainstem and hypothalamus, modulating food intake.

Phases of Gastrointestinal Control:

  • Cephalic Phase (before food enters stomach)

    • Triggered by sight, smell, taste, and thought of food

    • Increases salivary secretion and gastric acid secretion via parasympathetic stimulation (vagus nerve)

    • Prepares digestive tract for incoming food

  • Gastric Phase (food in stomach)

    • Gastric distension stimulates stretch receptors, enhancing acid and enzyme secretion

    • Gastrin hormone released, stimulating acid secretion and motility

  • Intestinal Phase (food enters small intestine)

    • Nutrients stimulate release of hormones like CCK and secretin

    • These regulate pancreatic juice secretion, bile secretion, and modulate gastric emptying

Salivary and Gastric Acid Secretion:

  • Salivary secretion:

    • Controlled by autonomic nervous system

    • Parasympathetic activation increases watery saliva with digestive enzymes

  • Gastric acid secretion:

    • Stimulated by acetylcholine (vagal), gastrin, and histamine

    • Acid aids protein digestion and activates pepsinogen to pepsin.

Cephalic-Phase Regulation of Secretion:

  • Vagal stimulation from the brain activates parietal cells (acid secretion) and chief cells (pepsinogen secretion)

  • Prepares stomach for digestion

Pancreatic Juice Secretion:

  • Stimulated by:

    • Secretin (released by S cells in response to acid in duodenum) stimulates bicarbonate-rich secretion to neutralize acid

    • CCK (released by I cells in response to fats and proteins) stimulates enzyme-rich pancreatic secretion

  • Both hormones modulate digestive enzyme release and maintain intestinal pH.

Regulation of Bile Secretion:

  • Bile is produced by the liver and stored in the gallbladder

  • Released in response to CCK, which causes gallbladder contraction and relaxation of the sphincter of Oddi

  • Bile emulsifies fats, facilitating their digestion and absorption

Gastrointestinal Motility:

  • GI motility refers to the coordinated muscular contractions that move and mix contents through the digestive tract. It is regulated by electrical activity, neural reflexes, hormones, and local factors to optimize digestion and absorption.

Electrical Activity:

  • Slow waves (basic electrical rhythm) are spontaneous oscillations in the membrane potential of smooth muscle cells, generated by interstitial cells of Cajal

  • Slow waves set the rhythm but do not always cause contraction; contractions occur when slow waves reach threshold, triggering spike potentials

  • Frequency of slow waves varies:

    • Stomach ~3/min

    • Small intestine ~12/min

    • Colon ~6/min

Types of Motility:

  • Peristalsis:

    • Propulsive wave-like contractions that move luminal contents forward

    • Coordinated contraction of circular muscles behind the bolus and relaxation ahead

  • Segmentation:

    • Rhythmic contractions that mix intestinal contents without net forward movement

    • Enhances digestion and absorption by mixing chyme with digestive enzymes and increasing contact with mucosa.

Patterns in Gastric Motility:

  • Receptive relaxation: stomach relaxes to accommodate incoming food

  • Mixing waves: weak peristaltic contractions mix food with gastric secretions

  • Strong peristaltic waves: propel chyme toward the pylorus

  • Pyloric sphincter regulates gastric emptying, allowing small amounts into the duodenum.

Phases of Regulation:

  • Cephalic phase: triggered by sight, smell, thought of food; increases gastric motility via vagal stimulation

  • Gastric phase: food in stomach stretches walls and stimulates gastrin release, increasing motility and secretion

  • Intestinal phase: presence of chyme in intestine modulates gastric motility; fats and acids slow gastric emptying via enterogastric reflex

Motility Reflexes:

  • Gastrocolic reflex: increased colonic motility after eating

  • Enterogastric reflex: inhibits gastric motility when intestine is irritated or full

  • Ileogastric and ileocecal reflexes: regulate flow from ileum to colon

Transit Rate:

  • Small intestine transit time: ~3–5 hours

  • Colon transit time: ~12–48 hours

  • Transit rate influenced by diet, hydration, neural and hormonal signals

Colon Motility:

  • Characterized by haustral contractions (slow segmentation) for mixing

  • Mass movements: powerful peristaltic waves moving feces toward rectum, usually 1–3 times/day

  • Defecation reflex triggered by rectal distension

Small Intestine Motility:

  • Mixes chyme by segmentation to enhance digestion and absorption

  • Peristalsis propels chyme slowly toward colon

  • Migrating motor complex (MMC) occurs in fasting state, clearing residual contents.

Vomiting:

  • Coordinated reflex involving reverse peristalsis, relaxation of the lower esophageal sphincter, and abdominal muscle contraction

  • Triggered by stimuli from the vomiting centre in the brainstem (e.g., toxins, vestibular system, GI irritation)

  • Protects against ingestion of harmful substances.