Digestive Physiology PDF

# Digestive Physiology ## Regions of the Small Intestine * Duodenum * Jejunum * Ileum ## Structure of a Villus * Microvilli - brush border * Crypt * Villi * Lacteal * Blood capillaries ## Digestive Physiology ### Lumen of Stomach * H₂O * H⁺ * H⁺ + OH<sup>-</s...

# Digestive Physiology ## Regions of the Small Intestine * Duodenum * Jejunum * Ileum ## Structure of a Villus * Microvilli - brush border * Crypt * Villi * Lacteal * Blood capillaries ## Digestive Physiology ### Lumen of Stomach * H₂O * H⁺ * H⁺ + OH^- * ATP * K⁺ * CA * HCO₃ * CO₂ * Cl^- * Cl^- * Cl^- * Cl^- * Parietal cell secretes hydrochloric acid. ### Gastric Emptying and Meal Caloric Content * 150 KCAL T1/2 = 57' * 300 KCAL T1/2 = 70' * 600 KCAL T1/2 = 95' ### (a) Fiber-rich Meal * Stomach * Small intestine ### (b) Low-fiber Meal * Stomach * Small intestine # The Physiology of the Digestive System ## The Digestive System Has Two 'Jobs' 1. **Converting bulky, complex food obtained from the environment into small molecular units the body can use:** DIGESTION * Complex polymers (starches, proteins, etc.) are reduced to simple subunits 2. **Moving the products of digestion from the gut lumen into the body: ABSORPTION** ## Two Additional Properties Facilitate These Functions: * **MOTILITY** * **SECRETION** # The Physiology of the Digestive System ## These four Processes Occur Within a Tubular 'Reactor' System With (Normally) One-Way Flow of Materials: | | | |---|---| | Lumen of digestive tract | Wall | | | | | Interstitial fluid | Blood | * Food * DIGESTION * MOTILITY * SECRETION * ABSORPTION # Digestive Physiology: Fluid Secretion and Absorption ## Large Volumes of Fluid Enter the Digestive Tract: * **In food and drink** * **Secretion from gut and various exocrine glands - salivary glands, liver, pancreas** | | | |---|---| | Fluid input into digestive system | Fluid removed from digestive system | | 2.0 L food and drink | | | 1.5 L saliva (salivary glands) | | | 0.5 L bile (liver) | Absorption | | 2.0 L gastric secretions | 7.5 L from small intestine | | 1.5 L pancreatic secretions | 1.4 L from large intestine | | 1.5 L intestinal secretions | Excretion | | 9.0 L Total input into lumen | 0.1 L in feces | | | 9.0 L removed from lumen | ## Overall, Fluid Input = Fluid Output (Most Fluid Is Absorbed) # Structural Commonalities in Major Organs ## Stomach * Esophagus * Fundus * Body * Antrum * Pylorus * Rugae: Surface folding increases area * Diaphragm ## Small Intestine * Mesentery * Mucosa * Submucosa * Plica * Circular muscle * Longitudinal muscle * Serosa * Submucosal glands * Villi ## Extensive Folding, Etc., To Increase the Surface Area ## 4 Layers: Mucosa (Lining Lumen), Submucosa, Longitudinal and Circular Smooth Muscle, and Serosa # Digestive Organs: Mouth ## The Mouth Is the Entry Point for Food Into the Digestive Tract * Saliva contains salivary amylase and lingual lipase, which begin to break down amylose (component of starch) and triglycerides respectively, as well as lysozymes and lactoferrins, which help to inhibit bacterial growth in the mouth. ## Chewing Mechanically Breaks Food Down, Increasing the Surface Area in Contact With Digestive Enzymes. # Digestive Organs: Mouth ## The Mouth Is the Entry Point for Food Into the Digestive Tract * Lysozymes enzymatically "punch” holes in the bacterial cell walls * Lysozymes catalyze hydrolysis of 1,4-β linkages in peptidoglycans (the proteins that comprise the bacterial cell wall) ## Dogs Have a Much Greater Concentration of Lysozymes, Which Protects Them From Infection When They're Rooting Around in the Garbage * Prokaryotic cell structure * Cytoplasm * Nucleoid * Capsule * Cell Wall * Cytoplasmic Membrane * Ribosomes * Pili * Flagella ## Lactoferrin = High-Affinity Fe-Binding Protein That Competes With Bacteria for Fe ## Lactoferrin Also Present in Milk, Tears, and Nasal Secretion → Innate Defense at Mucosal Surfaces → Deprives Bacteria of Fe (Essential Nutrient) * Iron-deficiency anemias around the world are associated with increased lactoferrin production – "the anemia of infection." # Digestive Organs: Stomach ## Main Digestive Functions: * **Mechanical breakdown** * 'Churning' of stomach contents * **Chemical digestion** * Low pH, protease (pepsin) * **Storage** - does not store food long-term, but allows a longer processing period for protein digestion before metering out in small boluses * Chyme # Digestive Organs: Stomach ## The Stomach Is Highly Distensible: * **Lined with internal folds (gastric rugae)** * **3x larger during big meals** * Full stomach - 3x (normal distension) * Distended stomach - competitive eater ## Extreme Distension Can Lead to Irreversible Stretching Which Can Cause Malnutrition, Vomiting, Etc. - Sx Reduction # Digestive Organs: Stomach * Fundus * Esophagus * Cardioesophageal Sphincter * Longitudinal muscle layer * Circular muscle layer * Diagonal muscle layer * Sphincter * Small intestine * Pylorus * Antrum ## Extensive Musculature for Mechanical Breakdown of Food # The Physiology of the Digestive System ## Two Forms of Gut Motility: 1. **Directional (forward) movement of material (via peristalsis)** 2. **Mixing of gut contents (via segmental contractions)** * Contraction * Bolus * Receiving segment * Time zero * Seconds later * Direction of movement * Bolus moves forward. # Digestive Organs: Stomach ## Detailed Stomach Anatomy: Gastric Glands in 'Pits' ## Several Cell Types in Gastric Gland Epithelium: Produce HCI, Mucus, Protease, Hormones, Etc. | | | | |---|---|---| | Gastric pits | | | | Surface epithelium | | Substance Secreted| | Mucus-secreting cells | Mucous neck cell | Mucus (protects lining) | | | | Bicarbonate | | Parietal cells | Parietal cells | Gastric acid (HCI) | | Gastric glands | | Intrinsic factor | | Chief cells | | B12 absorption | | | Enterochromaffin-like cell| Histamine (stimulates acid) | | | Chief cells | Pepsin(ogen) | | | | Gastric lipase | | | D cells | Somatostatin (inhibits acid) | | Mucosa | | | | | G cells | Gastrin (stimulates acid) | | Three smooth muscle layers | | | | Connective tissue | | | | Connective tissue | Lumen of stomach | | | | Cell types | | # Digestion and Absorption: Avoiding Autodigestion ## Various Parts of the Digestive Tract Produce Digestive Enzymes That Attack Standard Cellular Materials, Especially Proteins and Lipids ## Protective Mechanisms Against Autodigestion Include: * **Protective barriers (mucus, etc.) in digestive portions of Gl tract - these are reduced or absent in absorptive portions)** * **Production of many digestive enzymes in inactive forms (zymogens)** * Activated once safely inside lumen ## Pepsin Is Secreted as Pepsinogen, Which Is Activated by HCI in the Gastric Juice # Digestive Organs: Stomach ## 1-3 Liters/Day of Hydrochloric Acid Secreted by Parietal Cells * Stomach content pH ~ 1-2; parietal cell cytosol pH ~ 7.2: 2.5 million-fold [H⁺] gradient! ## Active Transport Necessary! * H⁺/K⁺ (proton) pump ## H⁺ Is Generated Via Carbonic Anhydrase, Then Exported to Lumen With Cl^- * H⁺ * ATP * K⁺ * Cl^- * Cl^- * H₂O * H⁺ + OH^- * CA * CO₂ * HCO₃^- * Cl^- * Cl^- * Parietal cell secretes hydrochloric acid. * Interstitial fluid * H₂ * Histamine * Gastrin * Gastrin ## As a Result, Blood Leaving Stomach During a Meal Is Quite Basic: 'Alkaline Tide' * Alkaline tide balanced by later bicarbonate secretion by pancreas; overall pH regulation via lungs and kidneys ## Hormonal Control: Gastrin Promotes Acid Secretion * (+ Histamine via H₂ receptors) # Digestive Organs: Stomach ## 1-3 Liters/Day of Hydrochloric Acid Secreted by Parietal Cells * Stomach content pH ~ 1-2; parietal cell cytosol pH ~ 7.2: 2.5 million-fold [H⁺] gradient! ## Active Transport Necessary! * H⁺/K⁺ (proton) pump ## H⁺ Is Generated Via Carbonic Anhydrase, Then Exported to Lumen With Cl^- * H⁺ * ATP * K⁺ * Cl^- * Cl^- * H₂O * H⁺ + OH^- * CA * CO₂ * HCO₃^- * Cl^- * Cl^- * Parietal cell secretes hydrochloric acid. * Interstitial fluid * Histamine * Gastrin * Gastrin ## The Drug Cimetidine (Tagamet®) Binds to and Blocks the H₂ Receptor - Tx for Acid Reflux ("Heartburn") and Stomach Ulcers * Alkaline tide balanced by later bicarbonate secretion by pancreas; overall pH regulation via lungs and kidneys * Hormonal control: gastrin promotes acid secretion * (+ Histamine via H₂ receptors) # Digestive Organs: Stomach ## 1-3 Liters/Day of Hydrochloric Acid Secreted by Parietal Cells * Stomach content pH ~ 1-2; parietal cell cytosol pH ~ 7.2: 2.5 million-fold [H⁺] gradient! ## Active Transport Necessary! * H⁺/K⁺ (proton) pump ## H⁺ Is Generated Via Carbonic Anhydrase, Then Exported to Lumen With Cl^- * H⁺ * A * K⁺ * Cl^- * Cl^- * H₂O * H⁺ + OH^- * CA * CO₂ * HCO₃^- * Cl^- * Cl^- * Parietal cell secretes hydrochloric acid. * Interstitial fluid * H₂ * Histamine * Gastrin * Gastrin ## The Drug Omeprazole (Prilosec®) Directly Inhibits the Proton Pump - Tx for Acid Reflux (“Heartburn”) and Stomach Ulcers (More Potent Than H₂ Histamine Blockers) * Alkaline tide balanced by later bicarbonate secretion by pancreas; overall pH regulation via lungs and kidneys * Hormonal control: gastrin promotes acid secretion * (+ Histamine via H₂ receptors) # Digestive Organs: Stomach ## 1-3 Liters/Day of Hydrochloric Acid Secreted by Parietal Cells * Stomach content pH ~ 1-2; parietal cell cytosol pH ~ 7.2 ## Need to Protect Gastric Mucosa From Acid in Lumen! ## Two Protective Mechanisms: * **Mucus layer ('armor')** * The mucus layer is a physical barrier. * **Bicarbonate secretion into mucus to buffer low pH** * Bicarbonate is a chemical barrier that neutralizes acid. * **Both produced by mucus neck cells in the gastric glands** ## **Gastric Juice pH ~ 2** * Stomach lumen * Mucus layer * HCO₃ * HCO₃ * pH ~ 7 at cell surface * Mucus droplets * Gastric mucous cell * Capillary # Digestive Organs: Stomach ## Why Is the Stomach So Acidic? 1. **As a barrier to bacteria entering the gut → lessens the bacterial load overall (some bacteria are resistant to low pH)** 2. **Allows a longer process of protein digestion → particularly useful for tough structural proteins (e.g., collagen)** ## What Does Acid Do to Proteins? - It Denatures Them ## What Does Denaturing Physically Do to a Protein? * The protein loses its quarternary and tertiary structure and "unfolds” – this allows the beneficial cofactors found in many proteins to be absorbed (e.g., Hb → Fe) ## **↓ pH → quaternary / tertiary bonds weaken → protein unfolds → more amino acid residues are exposed to proteases → cofactors, vitamins, trace metals are released for digestion/absorption** * Folded * Unfolded # The Determinants of Gastric Emptying ## Gastric Emptying Is Governed by Two Physical Properties of the Ingested Food (Chyme): 1. **Particle size** 2. **Energy content** ## **% of meal retained in stomach** * 100 * 50 * 0 * 0 * 30 * 60 * 90 * 120 * Liquid meal * Solid meal ## **Residual gastric volume (ml)** * 700 * 600 * 500 * 400 * 300 * 200 * 100 * 0 * 0 * 20 * 40 * 60 * 80 * Lipids * Proteins * Glucose ## Increased Particle Size and/or Increased Energy Content of Meal = Slower Gastric Emptying ## You Can Override This Process by Eating a Very Large Meal and Over-Distend the Stomach – (Think Thanksgiving) ## OR ## If You Force Open the Pyloric Sphincter With a Non-Digestible Foreign Object – (Drug Mules, Etc....Lots of Examples From U.S. Customs Service) # Small Intestine: Digestive Function ## Most Digestion Occurs in the Small Intestine * Digestion in small intestine partly due to products from liver (bile salts, etc.) and pancreas (various digestive enzymes) * Small intestine also secretes its own digestive enzymes * Many intestinal enzymes are attached to membranes of epithelial cells (not carried away and lost in the movement of chyme) * Alkaline pH (from bicarbonate produced in pancreas) # Pancreas: Bicarbonate and Digestive Enzymes ## Endocrine Functions: * Insulin and glucagon from islet cells; major regulatory hormones for energy metabolism ## Exocrine Functions: * Duct cells secrete bicarbonate to neutralize stomach acid * Acinar cells make several digestive enzymes * Lumen * 0 * 0 * 0 * 0 * 0 * 0 # Pancreas: Bicarbonate Secretion (Small Intestine Similar) * Powered (indirectly) by Na⁺-K⁺ ATPase * Dependent on carbonic anhydrase * Bicarbonate export to lumen via HCO₃^--Cl^- exchanger and CFTR channel (Cystic Fibrosis Transmembrane conductance Regulator) ## **Lumen of pancreas or intestine** * Pancreatic duct cell or duodenal cell * H₂O + CO₂ * CA * HCO₃ + H⁺ * Cl^- * HCO₃^- * CI^- * CFTR channel * Na⁺ * ATP * K⁺ * Na⁺ * 2 Cl^- * K⁺ * H₂O, * Na⁺ * Interstitial fluid * CO₂ * Capillary ## Mutation in CFTR Channel Leads to Cystic Fibrosis * Secretion of chloride and fluid decreased * Mucus is thickened (not diluted enough) * Also in lung → increased lung infections, scarring # Small Intestine: Absorptive Functions ## Regions of the Small Intestine * Duodenum * Jejunum * Ileum * Large intestine * Small intestine * Esophagus * Lumen * Plicae circulares (valves of Kerckring) * Stomach * Serosa * Circular muscle layer * Longitudinal muscle layer * ©2003 Encyclopædia Britannica, Inc. ## Structure of a Villus * Villus * Microvilli * Brush border * Crypt * Plica circularis * Villi * Lacteal * Blood capillaries * Epithelium * Absorptive cells (enterocytes) * Goblet cells * Endocrine cells * Intestinal gland (Lieberkühn gland) * Cells of Paneth ## Enlargement of Plicae Circulares ## Duodenum – Jejunum – Ileum ## Deconstructing the Surface Area (SA) of the Small Intestines: * SA = 1/3 m² if the small intestines were simply a smooth tube * SA = 1 m² – internal folding, intestinal wall (plicae circulares) * SA = 10 m² – villi * SA = 200 m² – microvilli * 600x increase in SA # Small Intestine: Absorptive Functions ## Regions of the Small Intestine * Duodenum * Jejunum * Ileum * Large intestine * Small intestine * Esophagus * Lumen * Plicae circulares (valves of Kerckring) * Stomach * Serosa * Circular muscle layer * Longitudinal muscle layer * ©2003 Encyclopædia Britannica, Inc. ## Structure of a Villus * Villus * Microvilli * Brush border * Crypt * Plica circularis * Villi * Lacteal * Blood capillaries * Epithelium * Absorptive cells (enterocytes) * Goblet cells * Endocrine cells * Intestinal gland (Lieberkühn gland) * Cells of Paneth ## Immune Diseases That Cause Inflammation (E.g., Food Allergies, Celiac Disease) Can Result in a Smoothing of the Surface Area in the Small Intestines → Malabsorption ## Duodenum – Jejunum – Ileum ## Deconstructing the Surface Area (SA) of the Small Intestines: * SA = 1/3 m² if the small intestines were simply a smooth tube * SA = 1 m² – internal folding, intestinal wall (plicae circulares) * SA = 10 m² – villi * SA = 200 m² – microvilli * 600x increase in SA # Small Intestine: Absorptive Functions ## Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. * Duodenum * Duodenojejunal flexure * Jejunum * Ileocecal valve * Ileum ## Upper 40% - CHO, Lipids, Proteins Absorbed ## Lower 60% - B12, Water, Electrolytes, Bile Salts Absorbed (Mostly in Ileum - Long in Humans) # Small Intestine: Absorptive Functions ## The Small Intestine Is the Primary Absorptive Organ in the Body for Nutrients ## All Absorbed Materials Must Pass Through the Epithelial (Mucosal) Cells Lining the Wall of the Small Intestine ## Water-Soluble Compounds Are Absorbed Into the Intestinal Capillaries → Portal System → Liver * Thin epithelium * Tiny lymphatic vessel (lacteal) * Villus * Blood capillary ## Fat-Soluble Compounds Are Absorbed Into Tiny Lymphatic Vessels Called Lacteals → Lymph System → General Circulation (Thoracic Duct) # Liver Function – Plumbing ## The Liver Is Highly Vascular and Has a Complex Circulatory Supply ## Inputs: * **Hepatic artery (blood from peripheral tissues)** * **Hepatic portal vein (blood from digestive tract)** ## Outputs: * **Hepatic vein (blood returning to heart)** * **Hepatic ducts (bile flow to gall bladder)** * Aorta * Hepatic vein * Capillaries of liver * Liver * Inferior vena cava * Hepatic artery * Capillaries of digestive tract: stomach, intestines, pancreas, and spleen * Hepatic portal vein * Digestive tract arteries # Liver Function – Complex, Multipurpose Biochemistry ## Absorbed From Gastrointestinal Tract * Bilirubin * Nutrients * Drugs * Foreign substances ## Hepatic Portal Vein ## Liver * Glucose and fat metabolism * Protein synthesis * Hormone synthesis * Urea production * Detoxification * Storage ## Hepatic Artery ## Metabolites and Drugs From Peripheral Tissues * Bilirubin * Metabolites of hormones and drugs * Nutrients ## Secreted Into Duodenum * Bile salts * Bilirubin * Water, ions * Phospholipids ## Bile Duct ## Hepatic Vein ## Metabolites to Peripheral Tissues * Glucose * Plasma proteins * Albumin, clotting factors * Angiotensinogen * Urea * Vitamin D, somatomedins * Metabolites for excretion ## Digestive Functions: * **Storage and production of glucose (liver "sees” insulin/glucagon first);** * Glycogen production from glucose (energy storage) * Gluconeogenesis (glucose production, mainly from amino acids) * **Detoxification** * **Production of bile (for lipid digestion in small intestine – emulsify large lipid droplets into small particles called micelles); stored and concentrated in gall bladder for controlled release** # Large Intestine – Anatomy & Function ## Large Intestine – No Microvilli, No Digestive Enzymes Secreted ## Mainly Waste Compaction, Salt and Water Reabsorption * Hepatic portal vein * Aorta * Tenia coli * Lymphoid nodule * Intestinal glands * Ascending colon * Ileocecal valve * Cecum * Appendix * Sigmoid colon * Rectum * Ileum * Muscularis mucosae *Submucosa * Descending colon * Haustra * Longitudinal layer (tenia coli) * Circular muscle * Muscularis externa * Rectum * Internal anal sphincter * External anal sphincter * Anus # Large Intestine - Ascending & Transverse Colon ## Bacterial Fermentation Factory * L→ * Digestion short-chain FFA (acetic acid) (water-soluble) * H₂S, CH₄, etc. * Microflora population ## Humans Are Not Able to Use Most of the Nutrients Synthesized by Bacteria in the Gut ## Other Organisms Can Better Utilize Bacterial Nutrients (E.g., Herbivorous Mammals) * (a) An African buffalo showing the size and position of the rumen * Rumen * Esophagus * Diaphragm * Hindgut vs. Foregut Fermenters * ANIMAL PHYSIOLOGY, Figure 4.14 (Part 1) © 2004 Sinauer Associates, Inc. # Reabsorption of Water and Salts (Small and Large Intestines) ## Large Quantities of Fluid Enter the Digestive Tract * By drinking and in food (roughly 2 liters/day) * Secretion by various gut organs (roughly 7 liters/day) ## Nearly All of This Is Absorbed (Or Reabsorbed) * Most fluid absorption in small intestine, some in large intestine * In a healthy person only a few hundred ml/day of fluid is lost in the feces ## MUCH more with diarrhea; some diarrheal diseases (e.g., cholera) result in severe and potentially fatal dehydration and solute loss # Large Intestine - (Transverse) & Descending Colon ## Descending Colon (and Transverse) Regulate Water / Salt Balance ## Enterocytes in the Small Intestine and Colonocytes in the Colon Absorb Na⁺ Using Three Different Transport Mechanisms * 'Powered' indirectly by Na⁺-K⁺ ATPase ## **Lumen of small intestine or colon** * Na⁺ * 1 * Na⁺ * CI^- * Na⁺ * H⁺ * HCO₃^- * CI^- * K⁺ * Intestinal cell * Na⁺ * 2 * Na⁺ * K⁺ * ATP * CI^- * CI^- * Interstitial fluid * Na⁺ * reabsorbed. ## Water Follows Osmotic Gradients Created by Solute Absorption 1. Na⁺ enters cells by multiple pathways. 2. The Na⁺- K⁺- ATPase pumps Na⁺ into the ECF. # Control of Digestion: Long (Central) and Short (Local) Reflexes ## Long Reflexes * Originate in the CNS; involve autonomic control (vagus nerve) * Parasympathetic NS * Stimulates GI tract * Sympathetic NS * Inhibits GI tract ## Short Reflexes * Originate in the enteric nervous system (within GI tract; local control) * Enteric plexus largely independent of CNS ## In Addition to Neural Control, There Is Also Hormonal and Paracrine Control (Gastrointestinal Peptides) * Food * Stomach * Lumen of stomach * Distension or peptides and amino acids initiate short reflexes. * Secretion and motility * Gastric mucosa * Sensory input * Effector cells * Food! * Medulla oblongata * Preganglionic parasympathetic neuron in vagus nerve * LONG REFLEX * SHORT REFLEX * Enteric plexus * M * Postganglionic parasympathetic and intrinsic enteric neurons # Control of Digestion: Three Phases of the Digestive Process ## Cephalic Phase (Seconds): * Digestive reflexes triggered by stimuli received in the brain * Response to the sight or smell (or thought) of food * Anticipatory (feed-forward) response; prepares the digestive system to process food ## Gastric Phase (≥ 30 Min.): * Storage of food in the stomach and the beginning of protein digestion leads to the production of chyme * Extensive hormonal and paracrine control (gastrin, histamine) ## Intestinal Phase (Hours): * Delivery of chyme to the intestines leads to digestion and absorption of nutrients and water and salt * Feedback control of delivery of chyme from stomach * Feedforward control of digestion and absorption * Hormonal and neural signaling # Human Physiology – BIOL 22 ## Next Time: Endocrinology I ## Silverthorn: 7 ## WELL ROOTS ## LIQUID-GEL DELIVERY ## COLON CLEANSE & LIVER DETOX ## Extra Strength Flush * Perfectly Balanced for Internal Cleansing and Detoxification * Featuring Milk Thistle, Aloe & More * 60 Fast-Acting Liquid Soft-Gels * Dietary Supplement ## This Is Your Liver. It Helps Your Body Get Rid of Toxins ## This Is a 'Detox' Supplement. It Helps Your Wallet Get Rid of Cash. ## Save Your Cash. If Your Liver Isn't Working, You Need a Hospital. ## fb.com/destroyedbyscience