Human Physiology: The Digestive System

Human Physiology: The Digestive System

Introduction

• Presented by Dr. Steven Patterson (Steven.Patterson@gcu.ac.uk).
• Covers the organs of the gastrointestinal (GI) tract and their functions.

Learning Outcomes

• Identify organs of the GI tract and accessory organs, and describe their basic functions.
• Describe the four layers forming the GI tract wall.
• Explain how the epithelial layer's structure and function vary in different parts of the GI tract.
• Name and identify the locations of salivary glands and the functions of their secretions.
• Describe the location, structure, and function of the esophagus, explaining how a food bolus is moved via peristalsis.
• Describe the location, structure, and functions of the stomach.
• Describe different cell types in gastric glands and their secretions' roles.
• Describe the functions of stomach acid and the consequences of overproduction.
• Give an account of digestion and absorption of nutrients in the stomach.
• Describe the small intestine's location, structure, and function, naming the three sections and their specific roles.
• Explain how plicae circulares, villi, and microvilli increase the surface area for digestion and absorption.
• Account for the digestion and absorption mechanisms of different nutrients (proteins, fats, and carbohydrates) in the small intestine.

Overview of the Digestive System

• Organs: Mouth, pharynx, esophagus, stomach, small intestine, large intestine, anus.
• Accessory Organs: Salivary glands, liver, gallbladder, pancreas.

Important Factors of the Digestive System

• Large surface area
• Absorption and secretion
• Exposure to diverse chemicals and microbes
• Motility
• Sensory input and regulation
• Immunity
• Regeneration and cell turnover
• Removal of waste

Functions of the Digestive System

• Processes food to extract nutrients for energy, growth, and tissue repair.
• Regulates body processes.
• Nutrients:
  • Macronutrients: carbohydrates (CHO), fats, proteins
  • Micronutrients: vitamins (water- and fat-soluble), minerals (Ca, Zn, Fe, Na, K, etc.)
  • Water
  • (Alcohol is not essential and thus not a nutrient).

Overall Process

• Food (CHO, fats, protein) is ingested.
• Digestion and absorption occur.
• Results in glucose, fatty acids, and amino acids.
• These are metabolized in cells (Krebs Cycle, etc.) to produce ATP for biological processes like muscle contraction.

Components of the Digestive System and Their Functions

• Oral Cavity/Mouth: Mechanical processing, moistening, mixing with salivary secretions.
• Teeth & Tongue: Mechanical processing.
• Salivary Glands: Secrete lubricating fluid with enzymes to break down carbohydrates.
• Pharynx: Muscular propulsion of materials into the esophagus.
• Esophagus: Transports materials to the stomach.
• Stomach: Chemical breakdown via acid and enzymes; mechanical processing through muscular contractions.
• Pancreas: Exocrine cells secrete buffers and digestive enzymes; endocrine cells secrete hormones.
• Liver: Secretion of bile (for lipid digestion); nutrient storage; many other vital functions.
• Gallbladder: Storage and concentration of bile.
• Small Intestine: Enzymatic digestion and absorption of water, organic substrates, vitamins, and ions.
• Large Intestine: Dehydration and compaction of indigestible materials for elimination.
• Anus: Elimination of waste.

Basic Processes of the GI Tract

• Ingestion: Eating
• Mechanical Digestion: Chewing, peristalsis, churning, etc.
• Chemical Digestion: Breakdown by enzymes
• Secretion: Bile, bicarbonate, enzymes
• Absorption: From GI tract into blood/lymph
• Excretion: Elimination of waste
• Transit time: 36-48 hours (variable).

Detail on Digestion and Absorption

• Digestion:
  • Mechanical: Chewing, mixing, and propulsion (smooth muscle contraction)
  • Chemical: Large molecules are broken down into small molecules by enzymes.
• Absorption:
  • Products of digestion move from epithelial cells into the blood or lymph, then to tissues.

Layers of the GI Tract Wall

• 1. Mucosa:
  • Inner layer of epithelium (absorptive & secretory function)
  • Lamina propria (connective tissue, blood vessels)
  • Muscularis mucosae (inner muscular layer)
• 2. Submucosa:
  • Connective tissue
  • Large blood and lymphatic vessels
  • Submucosal plexus (Meissner's plexus): network of neurons controlling secretions of the GI tract
• 3. Muscularis:
  • Smooth muscle layer
  • Inner circular layer (contraction narrows the gut)
  • Outer longitudinal layer (contraction shortens the gut)
  • Myenteric plexus (Auerbach's plexus) controls motility.
• 4. Serosa:
  • Outer layer of the gut
  • Forms the mesentery where nerves and blood vessels enter and leave the gut

Digestive Epithelium

• Simple (1 layer) or stratified (several layers), depending on location, function, and stresses.
• Oral cavity, pharynx, and esophagus:
  • Lined by stratified squamous epithelium for protection against mechanical stresses.
• Stomach, small intestine, and most of the large intestine:
  • Simple columnar epithelium with goblet cells for secretion and absorption.

Control of GI Tract

• Neuronal:
  • Myenteric plexus: Part of the enteric nervous system ('2nd brain') that controls motility.
  • Submucosal plexus: Regulates mucosal secretion
• Hormonal:
  • Gastrin, cholecystokinin (CCK), and others

Mouth (Oral Cavity) Functions

• Food is chewed (mastication) for mechanical digestion.
• Food is mixed with saliva from three pairs of salivary glands (99.5% water, digestive enzymes like amylase, mucus, ions, etc.).
• Food is formed into a bolus for swallowing (deglutition).

Salivary Glands

• Three Pairs: controlled by the autonomic nervous system (ANS)
• Produce 1.0–1.5 liters of saliva/day
  • 70% by submandibular glands (mixed serous & mucus)
  • 25% by parotid glands (serous, watery secretion + amylase, very little mucus)
  • 5% by sublingual glands (mainly mucus)
• Composition: 99.5% water + 0.5% salivary amylase + mucus + antibacterial enzymes.

Functions of Saliva

• Lubricates the mouth (easier to swallow; speech)
• Enzyme lysozyme kills bacteria; IgA antibodies are also protective
• Dissolves chemicals (stimulates taste buds)
• Buffers acidic foods (salivary pH ranges between 6.35 – 8.0)
• Starts digestion of carbohydrates (starch) by the enzyme salivary amylase into maltose (disaccharide).

Swallowing (Deglutition)

• Process involves the tongue, pharynx, and esophagus to move the bolus to the stomach.

Esophagus

• Collapsible muscular tube (about 25cm)
• Transports food to the stomach
• Sphincters at either end
• No digestion or absorption
• Goblet cells secrete mucus for lubrication and protection.
• The bolus is propelled down by PERISTALSIS.
  • Upper 1/3rd of muscularis: skeletal muscle
  • Middle 1/3 of muscularis: skeletal & smooth
  • Lower 1/3rd of muscularis: smooth muscle

Peristalsis

• Contraction & relaxation of muscle.
• Wave of contraction propels food (4-8 secs).
• Controlled & co-ordinated by myenteric plexus.
  • Circular muscle:
  • Contracts behind the bolus
  • Relaxes in front

Lower Esophageal Sphincter (Cardiac Sphincter)

• Controls entrance to the stomach.
• Ring of smooth muscle (normally contracted).
• Relaxes during swallowing.
• Sphincter contraction prevents reflux of stomach acid into the esophagus.
• Dysfunction leads to gastro-oesophageal reflux disease (GORD/GERD) and heartburn.

Clinical Conditions: Hiatus Hernia (Diaphragmatic Hernia)

• Occurs when part of the stomach protrudes through the diaphragm.

Stomach Functions

• Stores food.
• Mechanical digestion: softens food and mixes (3 layers of smooth muscle).
• Chemical digestion: secretes enzymes & HCl.
• Production of intrinsic factor: essential for Vitamin B12 absorption in the small intestine (needed for RBC synthesis); deficiency causes pernicious anaemia.

Stomach Anatomy

• Mucosa in folds (rugae) allows for expansion.

Stomach Regions

• Cardia
• Fundus
• Body
• Pylorus (controls exit from the stomach)

Stomach Lining

• Contains various cells in gastric glands.
  • Mucous cells: protect.
  • Parietal cells: produce HCl and intrinsic factor.
  • Chief cells: secrete digestive enzymes (inactive pepsinogen converted to active pepsin by HCl).
  • G cells: secrete gastrin (stimulates gastric juice secretion, ~1.0-1.5 L/day).

Functions of Acid in Stomach

• Kills most bacteria in food.
• Denatures proteins in food.
• Breaks down connective tissue in meat.
• Creates a very acidic environment (pH 1.5-2.0) for pepsin activation.
• Too much acid leads to peptic ulcers.

Peptic Ulcers

• Can be caused by H. pylori, aspirin, etc.
• May lead to bleeding or perforation (emergency situations).

Digestion & Absorption in Stomach

• Digestion:
  • Pepsinogen (inactive) converts to pepsin (active) via HCl.
  • Pepsin digests proteins into peptides.
  • Salivary enzymes are active until low pH denatures them (~1 hour).
• Absorption:
  • No nutrients are absorbed.
  • Some H2O, salts are absorbed.
  • Some drugs (alcohol, aspirin) are absorbed.

Small Intestine

• Segments: Duodenum, Jejunum, Ileum
• Length: ~6m / ~20ft long; 3 cm/ 1in wide
  -Duodenum (25cm/10in)
  -Jejunum (2.5m/8ft)
  -Ileum (3.5m/11ft)

Small Intestine Function

• Digestion & absorption of nutrients and water (90% of absorption occurs here).
• Duodenum: mixes chyme with pancreatic & liver/gallbladder secretions; neutralizes stomach acid.
• Jejunum: most digestion and absorption of nutrients takes place here.
• Ileum: specialist function - absorbs vitamin B12 & bile salts; has spare capacity.

Adaptations for Large Surface Area in Small Intestine

• Length: ~ 6m (20 ft)
• Plicae circulares (circular folds): transverse folds in the mucosa (permanent).
• Villi: finger-like projections increasing surface area for absorption (not found in stomach or colon).
• Microvilli: Further increase surface area (brush border; 250 m^2 = tennis court).

Intestinal Glands (Crypts of Lieberkuhn)

• Located at the bases of villi.
• Secrete intestinal juice (1-2 L/day): water & mucus.
• Slightly alkaline.
• Contain endocrine cells that secrete hormones into the blood (CCK & secretin).

Brunner’s Glands

• Submucosal glands of the duodenum.
• Produce alkaline mucus when acidic chyme arrives from the stomach.
• Only in the duodenum (not jejunum or ileum).

Coeliac Disease

• Autoimmune disease leading to flattened villi.
• Reduced absorptive surface results in malabsorption of nutrients.

Steatorrhea

• Excessive fat in stools due to fat malabsorption.

Brush Border Enzymes

• Integral membrane proteins on the surfaces of intestinal microvilli.
• Break down materials in contact with the brush border.
• Examples: maltase, lactase, sucrase (break down disaccharides to monosaccharides).
• Lactose intolerance: lack of lactase -> undigested lactose -> bloating, pain, diarrhea.

Mechanical Digestion in Small Intestine

• Peristalsis: Propulsive contractions.
• Segmentation: Churns and fragments the bolus; non-propulsive; mixes contents with intestinal secretions.

Chemical Digestion in Small Intestine: CHO Digestion

• Polysaccharides (starch) are broken down into disaccharides (maltose) by amylase (salivary glands & pancreas).
• Disaccharides are broken down into monosaccharides (glucose, fructose, galactose) by brush border enzymes.

Brush Border Enzymes for CHO Digestion

• Maltase: Breaks down maltose into 2 molecules of glucose.
• Sucrase: Breaks down sucrose into glucose and fructose.
• Lactase: Breaks down lactose into glucose and galactose.

Digestion of Proteins

• Proteins and large polypeptides are broken down into peptides by pepsin (stomach) and pancreatic proteases.
• Peptides are further broken down into amino acids by brush border enzymes.

Proteases

• Pancreatic proteases: trypsin, chymotrypsin, carboxypeptidase, elastase.
• Must be released in inactive forms to prevent digestion of the pancreas itself.

Fat (Lipid) Digestion

• Dietary fats (triglycerides) are not water-soluble.
• Mechanical processing (stomach) creates large fat droplets.
• Pancreatic lipase, being water-soluble, can only act at the surface of the lipid droplet.
• Bile salts are needed to break down the droplet into smaller droplets (emulsification).

Role of Bile Salts (1st Role)

• Bile salts break droplets apart (emulsification), creating tiny emulsion droplets coated with bile salts.
• Increases the surface area for lipase to act.

Digestion of Fats - Triglycerides

• Triglycerides are broken down by pancreatic lipase into monoglycerides + 2 free fatty acids.

Absorption Mechanisms

• 90% of absorption occurs in the small intestine (mainly jejunum).
• Very large surface area due to:
  • Length
  • Presence of circular folds (plicae circulares)
  • Villi
  • Microvilli (a 600-fold increase in surface area)

Transport Mechanisms

• Through luminal surface
• Through cytoplasm
• Through basolateral membrane.
• Uptake into blood stream

Paracellular Transport

• Water and other small water-soluble molecules may also cross via paracellular transport (i.e. between tight junctions).

Simple Diffusion

• Molecules move down their concentration gradient.
• Fatty acids, alcohol, and dissolved gases diffuse through the lipid portion of the cell membrane.
• Water & some ions pass through tiny membrane channels.
• Bigger water-soluble molecules (e.g., glucose, amino acids) are too big to fit through channels and use carrier proteins (facilitated diffusion).

Facilitated Diffusion

• Uses carrier proteins to move molecules down their concentration gradient.

Co-transport (Secondary Active Transport)

• Both receptor sites must be filled for transport to occur.
• Na+ diffuses down its concentration gradient and is then actively pumped back out of the cells.
• SGLT1 is an example.

Absorption of CHO & Amino Acids

• Glucose/galactose: Co-transport + Na+ (BOTH must bind to the carrier).
• Fructose: Facilitated diffusion (carrier-mediated; moves down the concentration gradient).
• Amino acids: Absorbed by both facilitated diffusion and co-transport.

Absorption of fats (2nd role of Bile salts)

• Long-chain fatty acids & monoglycerides + Bile salts form micelles.
• Micelles: water-soluble; diffuse to mucosa; FA & monoglyceride diffuse into epithelial cell by simple diffusion.
• Short/medium-chain FAs go directly into villus blood.

Summary of Fat Absorption

• Within epithelial cells, triglycerides are re-formed from monoglycerides & free fatty acids.
• Coated with protein (mostly apoB48) to form chylomicrons.
• Chylomicrons: are too big to enter capillaries so they enter lacteals (lymphatics) and then the systemic circulation (left subclavian vein).
• The blood has a ‘milky’ appearance.

Cholesterol Absorption

• Cholesterol esters are de-esterified by enzymes in the small intestine to yield free cholesterol.
• Forms micelles with bile salts and phospholipids.
• Micelle reaches the brush border.
• Neimann-Pick C1 Like-1 (NPC1L1) is a membrane transport protein for cholesterol and other sterols.
• Inside cells, cholesterol is re-esterified.

Absorption of Products of Digestion

• Monosaccharides and amino acids are absorbed into blood capillaries and transported via the hepatic portal vein to the liver.
• Short-chain fatty acids are absorbed into blood capillaries.
• Chylomicrons are absorbed into lacteals and transported via the lymphatic system, eventually entering the bloodstream at the left subclavian vein.