The Three Phases of Digestion 1. Cephalic Phase (Neurogenic Phase) - Duration : Before and during eating - Stimuli : Sight, smell, taste, thought of food - Mech
The Three Phases of Digestion 1. Cephalic Phase (Neurogenic Phase) - Duration : Before and during eating - Stimuli : Sight, smell, taste, thought of food - Mechanism : Vagal stimulation (parasympathetic) - Effects : - Salivary secretion increases - Gastric acid secretion begins (30% of total) - Pancreatic enzyme secretion starts - Gastrin release from G cells 2. Gastric Phase - Duration : When food enters stomach - Stimuli : Gastric distension, amino acids, peptides - Mechanism : Local reflexes + vagal reflexes - Effects : - Gastric acid secretion peaks (60% of total) - Pepsinogen secretion - Gastrin release continues - Gastric motility increases 3. Intestinal Phase - Duration : When chyme enters duodenum - Stimuli : Amino acids, fatty acids, glucose in duodenum - Mechanism : Hormonal (CCK, secretin, GIP) - Effects : - Inhibits gastric acid secretion (10% of total) - Stimulates pancreatic enzyme and bicarbonate secretion - Stimulates bile release - Regulates gastric emptying --- CARBOHYDRATE DIGESTION AND ABSORPTION Step-by-Step Digestion Process 1. Mouth - Enzyme : Salivary α-amylase (ptyalin) - Action : Hydrolyzes α-1,4-glycosidic bonds in starch - Products : Maltose, maltotriose, α-limit dextrins - pH : Optimal at 6.8 2. Stomach - Process : Salivary amylase inactivated by gastric acid - Result : Minimal carbohydrate digestion 3. Small Intestine - Lumen - Enzyme : Pancreatic α-amylase - Action : Continues starch breakdown - Products : Maltose, maltotriose, α-limit dextrins - pH : Optimal at 8.0 4. Small Intestine - Brush Border - Enzymes and Actions : - Maltase : Maltose → Glucose + Glucose - Isomaltase (α-dextrinase) : α-limit dextrins → Glucose - Sucrase : Sucrose → Glucose + Fructose - Lactase : Lactose → Glucose + Galactose - Trehalase : Trehalose → Glucose + Glucose Absorption Mechanisms Glucose and Galactose Absorption - Luminal Membrane : - Transporter : SGLT1 (Sodium-Glucose Linked Transporter 1) - Mechanism : Secondary active transport (Na+-dependent cotransport) - Stoichiometry : 2 Na+ : 1 glucose/galactose - Energy : Uses Na+ gradient created by Na+-K+ ATPase - Basolateral Membrane : - Transporter : GLUT2 (Glucose Transporter 2) - Mechanism : Facilitated diffusion - Direction : Cell → Blood → Portal circulation Fructose Absorption - Luminal Membrane : - Transporter : GLUT5 - Mechanism : Facilitated diffusion (Na+-independent) - Limitation : Cannot be absorbed against concentration gradient - Basolateral Membrane : - Transporter : GLUT2 - Mechanism : Facilitated diffusion Key Point : SGLT2 is found in the kidneys (proximal tubule), not intestines! --- PROTEIN DIGESTION AND ABSORPTION Step-by-Step Digestion Process 1. Stomach - Enzyme : Pepsin (from pepsinogen) - Activation : Pepsinogen → Pepsin (by gastric HCl) - Action : Endopeptidase (cleaves interior peptide bonds) - pH : Optimal 1.5-3.5 - Products : Large peptides and polypeptides 2. Small Intestine - Pancreatic Enzymes - Activation Cascade : - Enterokinase (brush border) → Trypsinogen to Trypsin - Trypsin → Activates all other pancreatic proteases - Enzymes : - Trypsin : Endopeptidase (cleaves after basic amino acids) - Chymotrypsin : Endopeptidase (cleaves after aromatic amino acids) - Elastase : Endopeptidase (cleaves after small amino acids) - Carboxypeptidase A : Exopeptidase (removes aromatic/basic AA from C-terminus) - Carboxypeptidase B : Exopeptidase (removes basic AA from C-terminus) 3. Small Intestine - Brush Border - Enzymes : Aminopeptidases, dipeptidases, tripeptidases - Products : Free amino acids, dipeptides, tripeptides Absorption Mechanisms Free Amino Acids - Luminal Membrane : - Transporters : Four separate Na+-dependent cotransporters Neutral amino acids : System B⁰ (broad specificity) - Acidic amino acids : System X⁻ₐᴳ - Basic amino acids : System b⁰⁺ - Imino acids : System IMINO - Mechanism : Secondary active transport - Basolateral Membrane : - Mechanism : Facilitated diffusion - Transporters : Various amino acid transporters Dipeptides and Tripeptides - Luminal Membrane : - Transporter : PEPT1 (Peptide Transporter 1) - Mechanism : H+-dependent cotransport - Advantage : Faster absorption than free amino acids - Intracellular : - Process : Cytoplasmic peptidases hydrolyze to amino acids - Exit : Amino acids exit via basolateral facilitated diffusion --- LIPID DIGESTION AND ABSORPTION Step-by-Step Digestion Process 1. Mouth - Enzyme : Lingual lipase - Action : Hydrolyzes short- and medium-chain triglycerides - Contribution : Minimal (continues in stomach) 2. Stomach - Enzyme : Gastric lipase - Action : Hydrolyzes triglycerides → fatty acids + diglycerides - Contribution : ~15% of total fat digestion - Physical : Churning creates lipid droplets 3. Small Intestine - Bile Acid Action - Source : Bile acids from liver/gallbladder - Function : Emulsification (↑ surface area) - Process : Large lipid droplets → smaller droplets 4. Small Intestine - Pancreatic Enzymes - Pancreatic lipase : Triglycerides → 2-monoglycerides + fatty acids - Cholesterol ester hydrolase : Cholesterol esters → cholesterol + fatty acids - Phospholipase A2 : Phospholipids → lysophospholipids + fatty acids - Cofactor : Colipase (helps lipase bind to lipid droplets) 5. Micelle Formation - Components : Bile acids + fatty acids + monoglycerides + cholesterol - Function : Solubilize hydrophobic products - Size : 2-10 nm diameter Absorption Mechanisms Fatty Acids, Monoglycerides, and Cholesterol - Luminal Membrane : - Mechanism : Passive diffusion from micelles - Transporters : CD36 : Fatty acid transporter - FATP4 : Fatty acid transport protein 4 - NPC1L1 : Cholesterol transporter - Intracellular Processing : - Fatty acid activation : Acyl-CoA synthetase - Re-esterification :Fatty acids + monoglycerides → triglycerides - Cholesterol → cholesterol esters - Formation of phospholipids Chylomicron Formation and Transport - Intracellular Assembly : - Core : Triglycerides + cholesterol esters - Surface : Phospholipids + cholesterol + apolipoproteins - Key apolipoprotein : ApoB-48 (essential for assembly) - Secretion : - Mechanism : Exocytosis from basolateral membrane - Destination : Lymphatic system (too large for capillaries) - Route : Thoracic duct → systemic circulation Medium-Chain Fatty Acids (C6-C12) - Absorption : Direct portal circulation (bypass lymphatic system) - Reason : Water-soluble, don't require micelles or chylomicrons --- LIPOPROTEIN TRANSPORT SYSTEM Chylomicrons - Origin : Intestinal cells - Function : Transport dietary lipids - Destination : Tissues via lymphatic system - Metabolism : Hydrolyzed by lipoprotein lipase VLDL (Very Low-Density Lipoproteins) - Origin : Liver - Function : Transport endogenous triglycerides - Apolipoprotein : ApoB-100 LDL (Low-Density Lipoproteins) - Origin : VLDL metabolism - Function : Cholesterol transport to tissues HDL (High-Density Lipoproteins) - Origin : Liver and intestine - Function : Reverse cholesterol transport --- CLINICAL CORRELATIONS Carbohydrate Disorders - Lactose Intolerance : Lactase deficiency → osmotic diarrhea - Glucose-Galactose Malabsorption : SGLT1 deficiency Protein Disorders - Hartnup Disease : Neutral amino acid transporter defect - Cystinuria : Basic amino acid transporter defect Lipid Disorders - Steatorrhea : Fat malabsorption - Pancreatic insufficiency - Bile acid deficiency - Intestinal disease - Abetalipoproteinemia : ApoB deficiency → no chylomicron formation --- SUMMARY: PORTAL CIRCULATION PATHWAY Water-Soluble Nutrients (Carbohydrates, Proteins, Water-soluble vitamins) Intestinal cell → Portal blood → Liver → Systemic circulation Fat-Soluble Nutrients (Fats, Fat-soluble vitamins) Intestinal cell → Chylomicrons → Lymphatic system → Thoracic duct → Systemic circulation --- KEY TRANSPORTERS SUMMARY Remember: SGLT2 is in the kidneys , not the intestines! --- GASTROINTESTINAL HORMONES GASTRIN - Source : G cells in gastric antrum and duodenum - Stimulus : - Amino acids and peptides in stomach - Gastric distension - Vagal stimul