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The Digestive System-Chapters 62-66; 70; 78 Figure 62-1; Guyton & Hall 1 Digestive Processes Ingestion Propulsion Digestion: Mechanical and Chemical digestion Absorption- nutrients and water Defecation 2 Layers Alimentary Canal 1. Serosa 2. Longitudinal muscle (muscularis externa) 3. Myenteric (Auerbach’s) nerve plexus 4. Circular muscle 5. Submucosa 6. Submucosal (Meissner’s) nerve plexus 7. Muscularis mucosae 8. Mucosa 9. Epithelial lining 3 Autonomic nerve fibers Both divisions found in myenteric and submucosal nerve plexi— What do they do? Sensory neurons that monitor tension, and efferent visceral motor fibers. OWN SYSTEM! Myenteric-GI motility control - Stimulatory influences • tonic contraction (tone) • contraction frequency / intensity ( propulsion) - Inhibitory influences • Decreased Sphincter tone (relax) - pyloric sphincter, ileocecal sphincter, LES Submucosal- Local control Secretion Absorption Contraction of muscularis mucosa 4 Control of the digestive system Movement of materials along the digestive tract is controlled by: Neural mechanisms Hormonal mechanisms Parasympathetic (Ach) and local reflexes Enhance or inhibit smooth muscle contraction Local mechanisms Coordinate response to changes in pH or chemical stimuli and stretching 5 Digestive Enzymes Salivary glands -amylase lingual lipase Stomach pepsin Pancreas amylase trypsin chymotrypsin carboxypeptidase lipase cholesterolesterase Intestinal Mucosa enterokinase sucrase maltase lactase aminooligopeptidase dipeptidase 6 The mouth opens into the oral or buccal cavity Primary Secretion Alpha-amylase Its functions include: Analysis of material before swallowing Mechanical processing by the teeth, tongue, and palatal surfaces Lubrication Limited digestion Lingual lipase (negligible fat digestion) Salivary amylase (limited carbohydrate digestion) Antibodies and proteolytic enzymes 7 Digestion and absorption in the stomach Short-term storage reservoir Secretion of intrinsic factor Pepsinogen gastrin Chemical and enzymatic digestion is initiated, particularly of proteins Liquefaction of food Slowly released into the small intestine for further processing 8 Gastric glands Two types glands - Gastric (oxyntic) HCl - Pyloric - gastrin mucus pepsinogen intrinsic factor mucus 9 Gastric glands- 3 types of cells Mucous Neck cell (goblet)- release mucus to protect mucosa from acid and pepsin Parietal cells- HCl and intrinsic factor (B12 absorption by small intestine). Chief- numerous and release pepsinogen 80% 10 Acid production and secretion LUMEN BLOOD HO- + H+ H2 O CO2 CO2 HCO HCO 3 3 K+ Na+ ClH2 O P C.A. K+ K+ Na+ Na+ P K+ P Cl- Cl - osmosis Na+ P H+ H2 O Cl- Final Results HCl - 155 mEq/L KCl - 15 mEq/L NaCl - 3 mEq.L pH = 0.8 11 2 cell types of Pyloric gland G-cells - release gastrin Enteroendocrine cells stimulates parietal cells to secrete acid and increases pyloric contraction; relaxes pyloric sphincter 20% Mucus neck cells - mucous 12 Gastric and Duodenal ulcers Weakens H. pylori, aspirin, ethanol, NSAIDs, bile salts Strengthens mucus, HCO3- secretion, gastrin, PGs, epidermal growth factor Peptic ulcers occur when damaging effects of acid and pepsin overcome ability of mucosa to protect itself Gastric ulcers - main problem is decreased ability of mucosa to protect itself Duodenal ulcers - main problem is exposure to increased amounts of acid and pepsin 13 What is the Gastric Mucosal Barrier? alkaline mucus resists the acid and enzymes Tight junctions-gastric juice can’t seep into lamina propria Epithelial cell replacement- 3-6 day life span. Physiological - diffused H+ ions are transported back to lumen Damaged Gastric Mucosal Barrier H+ back-leaks into mucosa in exchange for Na+. This is a forerunner to gastric ulcer Decreased cell pH leads to cell death Damaged mast cells (ECL cells) leak histamine Viscous cycle - Histamine .. vascular damage .. local ischemia .. greater leakage of H+.. more cell death ... 14 Helicobacter pylori H. pylori found in 95% patients with DU and 100% patients with GU (when alcohol, aspirin, NSAIDS are eliminated) Gram negative bacterium High urease activity - high NH4+ activity - can withstand acid environment - NH4+ damages epithelial cells (GU) - Increases acid secretion (DU) 15 Treatment of Peptic Ulcers Antacids H2 receptor blockers - Rantidine (Zantac) - Cimetidine (Tagamet) Proton pump inhibitors - Omeparazole (Prilosec) Antibiotics Surgical (rare) - vagotomy - antrectomy 16 Stimulation of acid secretion Gastric secretion is stimulated by local (distention), neural, and endocrine mechanisms Acetylcholine - HCl secretion - mucus, pepsinogen, and gastrin Histamine - HCl secretion Gastrin - HCl secretion (1500x more powerful compared to histamine) Seeing, smelling and anticipating food is perceived in brain. Brain tells stomach to prepare for receipt of meal Accounts for 30% of acid response to meal 60% 10% 17 Small intestine Important digestive and absorptive functions Three subdivisions: Secretions and buffers provided by pancreas, liver, gall bladder Duodenum Jejunum Ileum Ileocecal sphincter Transition between small and large intestine 18 Histology of the small intestine Plicae Transverse folds of the intestinal lining Villi Fingerlike projections of the mucosa Lacteals Terminal lymphatic in villus Microvilli Brush border: increases surface area 20-fold 19 Intestinal glands secretin to stimulate pancreas to release bicarbonate mucus cholecystokinin to stimulate pancreas and gallbladder Gastric Inhibitory peptide (GIP)inhibits gastrin secretion and decreases stomach emptying Duodenal glandsbicarbonate mucus. 20 The Activities of Major Digestive Tract Hormones 21 Figure 24.22 Small Intestine- digestive enzymes Maltase- splits maltose into 2 glucose units Lactase- splits lactose into glucose and galactose Sucrase- splits sucrose into glucose and fructose Peptidase- breaks down small peptides into amino acids Intestinal lipase- breaks down triglycerides into free fatty acids and monoglycerides Enterokinase- Activates trypsinogen to trypsin (trypsin then activates chymotrypsinogen and procarboxypeptidase) 22 Pancreas As chyme floods into small intestine two things must happen: Acid must be neutralized to prevent damage to duodenal mucosa Macromolecular nutrients - proteins, fats and starch must be broken down much further so their constituents can be absorbed Pancreas plays vital role in accomplishing both objectives Digestive enzymes for all food types Bicarbonate solution to neutralize acid chyme 23 Regulation of Pancreatic Secretion Secretin and CCK are released when fatty or acidic chyme enters the duodenum CCK and secretin enter the bloodstream Upon reaching the pancreas: CCK induces the secretion of enzyme-rich pancreatic juice Secretin causes secretion of bicarbonate-rich pancreatic juice Vagal stimulation also causes release of pancreatic juice 24 The Pancreas Exocrine function (98%) Acinar cells make, store, and secrete pancreatic enzymes Endocrine function – ( cells) release somatostatin (inhibitory to gastrin and insulin and glucagon) β-cells –release insulin α-cells-Release glucagon 25 The Pancreas as an Endocrine Gland Insulin Beta cells Skeletal muscle and adipose tissue need it to make glucose receptors Promotes glucose uptake Prevents fat and glycogen breakdown and inhibits gluconeogenesis Increases protein synthesis Promotes fat storage Epi/Norepi inhibit insulin! Help maintain glucose levels during times of stress and increase lipase activity in order to conserve glucose levels 26 Picture from:http://www.dkimages.com/discover/Home/Health-and-Beauty/Human-Body/Endocrine-System/Pancreas/Pancreas-1.html The Pancreas as an Endocrine Gland Glucagon Maintains blood glucose between meals and during periods of fasting. Nervous tissue (brain) do not need insulin; but are heavily dependent on glucose levels! Increases blood glucose levels. Initiates glycogenolysis in liver (within minutes) Stimulates amino acid transport to liver to stimulate gluconeogenesis Image from: http://www.dkimages.com/discover/previews/768/74261.JPG 27 Disorders of the Pancreas: Diabetes Mellitus Gestational Diabetes Type I diabetes – develops suddenly, usually before age 15 Destruction of the beta cells Skeletal tissue and adipose cells must use alternative fuel and this leads to ketoacidosis Hyperglycemia results in diabetic coma 28 Disorders of the Pancreas: Diabetes Mellitus Type II diabetes and metabolic syndrome– adult onset Usually occurs after age 40 Cells have lowered sensitivity to insulin Controlled by dietary changes and regular exercise 29 30 Pancreatic Failure Digestion is abnormal when pancreas fails to secrete normal amounts of enzymes. Pancreatitis Removal of pancreatic head - malignancy Without pancreatic enzymes - 60% fat not absorbed (steatorrhea) 30-40% protein and carbohydrates not absorbed 31 Pancreatitis Pancreatitis means inflammation of pancreas. Autodigestion theory can explain condition. Chronic pancreatitis - (multiple shared causes) alcohol - most common cause in adults cystic fibrosis - most common cause in childre CF patients lack chloride transporter at apical membrane. Watery ductal secretion decreases which concentrates acinar secretions in ducts. Precipitation of proteinaceous secretions block ducts and can destroy gland by autodigestion. Acute pancreatitis - (multiple shared causes) Gallstones - most common cause 32 Absorption of digested polymers is linked to Salt Absorption in Small Intestine • Sodium is absorbed across apical cell membrane by 4 mechanisms 1. 2. 3. 4. • Diffusion - through water-filled channels Co-transport - with AA and glucose Co-transport - with chloride Counter-transport - in exchange for H+ Chloride follows electrical gradient created by absorption of sodium 33 Sodium Absorption in Small Intestine 1 2 3 4 Aldosterone increases Na+ reabsorption and K+ secretion in S.I. and colon. Na+ Na+ Na+ S S Na+ Na+ Cl- ClNa+ H+ Na+ Cl- Na+ K+ Na+ K+ P Na+ H+ Cl34 Chemical Digestion: Carbohydrates Begins in the mouth (minimal) and mostly occurs in small intestine when pancreatic enzymes are released Absorption of monosaccharides occurs across the intestinal epithelia Absorption: via cotransport with Na+, and facilitated diffusion Enter the capillary bed in the villi Transported to the liver via the hepatic portal vein lumen Enzymes used: salivary amylase, pancreatic amylase, and brush border enzymes (maltase, lactase, and sucrase) 35 Chemical Digestion: Proteins Absorption: similar to carbohydrates (sodium cotransport) Enzymes used: pepsin in the stomach Enzymes acting in the small intestine Pancreatic enzymes – trypsin, chymotrypsin, and carboxypolypeptidase (these must be activated!) Brush border enzymes – peptidases 36 Lipid digestion and absorption Lipid digestion utilizes lingual and pancreatic lipases, cholesterol esterase (cleaves ester bond to release cholesterol) and phospholipases release fatty acids and monoglycerides. Bile salts improve chemical digestion by emulsifying lipid drops Lipid-bile salt complexes called micelles are formed 37 Fatty Acid Absorption Fatty acids and monoglycerides enter intestinal cells via diffusion; bile salts can be reused to ferry more monoglycerides They are combined with proteins within the cells Resulting chylomicrons are extruded They enter lacteals and are transported to the circulation via lymph 38 Sprue • Diseases that result in decreased absorption even when food is well digested are often classified as “sprue” - Nontropical sprue - also called celiac disease - allergic to gluten (wheat, rye) - Tropical sprue • - destroys microvilli and sometimes villi - bacterium (?) - treated with antibacterial agents Steatorrhea - if stool fat is in the form of FFA - digestion has occurred 39 Fluid Entering and Exiting the Gut Volume absorbed 8 Diet (2) 6 Saliva (1) Stomach (2) Duodenum and Jejunum (4) Volume (L/day) 10 Volume entering 4 2 0 Bile (1) Ileum (3.5) •95% of water is absorbed in the small intestines by osmosis •Water moves in both directions across intestinal mucosa •Net osmosis occurs whenever a concentration gradient is established by active transport of solutes into the mucosal cells Colon (1.4) Volume Excreted 100-200 ml Pancreas (1) S.I. (2) 40 The Liver Digestive function – bile production; emulsifies fats Bilirubin- decomposed hemoglobin Urobilinogen- byproduct of bilirubin metabolism bile salts- keep cholesterol dissolved in bile Performs many metabolic functions- stores vitamins, processes fats, detoxifies, makes blood proteins 41 Physiology of the large intestine Reabsorption in the large intestine includes: Water and electrolets Bacteria make: Vitamins – K, biotin, and B5 Organic wastes – urobilinogens and sterobilinogens Bile salts Toxins Mass movements of material through colon and rectum Defecation reflex triggered by distention of rectal walls 42 Figure 8-18 Agents that stimulate and inhibit H+ secretion by gastric parietal cells. ACh, Acetylcholine; cAMP, cyclic adenosine monophosphate; CCK, cholecystokinin; ECL, enterochromaffin-like; IP3, inositol 1,4,5-triphosphate; M, muscarinic. Downloaded from: StudentConsult (on 23 April 2010 06:51 PM) © 2005 Elsevier Figure 8-19 Regulation of HCl secretion during cephalic and gastric phases. ACh, Acetylcholine; GRP, gastrin-releasing peptide (bombesin). Downloaded from: StudentConsult (on 23 April 2010 06:51 PM) © 2005 Elsevier Figure 8-20 Balance of protective and damaging factors on gastroduodenal mucosa. H. pylori, Helicobacter pylori; NSAIDs, nonsteroidal antiinflammatory drugs. Downloaded from: StudentConsult (on 23 April 2010 06:51 PM) © 2005 Elsevier Figure 8-15 Secretory products of various gastric cells. Downloaded from: StudentConsult (on 23 April 2010 06:51 PM) © 2005 Elsevier