Gastrointestinal Physiology: A Global Overview Prepared and presented by Marc Imhotep Cray, M.D.
Image Plates from: Klatt EC. Ch.7 - The Gastrointestinal Tract : In: Robbins and Cotran Atlas of Pathology, 3rd Ed. Philadelphia. PA : Saunders, 2015; 193-200.
nml stomach, gross
Marc Imhotep Cray, M.D. colon, nml transverse
endoscopy
nml stomach, endoscopy
nml esophagus, endoscopy
nml esophagus, micro
nml sm intestine and mesentery, gross
Marc
Photo: Colorized computed tomographic (CT) scan of an axial section through the abdomen. The image shows a gallstone (pink) obstructing the bile duct where it leaves the gallbladder (green circle). The large yellow region around the gallbladder is the liver. a spine vertebra (pink) is visible in bottom center, with C-shaped kidneys (yellow) on either side. Imhotep Cray, M.D. From: Seeley’s Anatomy & Physiology 10th ed New York, NY: McGraw-Hill 2010
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Learning outcomes After studying this presentation, you should be able to: 1. List the functions of the digestive system. 2. Describe the microscopic structure of the gastrointestinal tract. 3. Describe the structure and functions of the esophagus and stomach. 4. Describe the composition and actions of gastric juice and explain how gastric secretion is regulated. 5. Describe the structure and functions of the small intestine. 6. Identify the location and describe the functions of the digestive enzymes of the small intestine. 7. Describe the muscle contractions and movements of the small intestine. 8. Describe the structure and functions of the large intestine. 9. Explain the nature and significance of the intestinal microbiota.
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Learning outcomes cont. After studying this presentation, you should be able to: 10. Describe the structure and functions of the liver. 11. Describe the synthesis, composition, and functions of bile and explain the enterohepatic circulation. 12. Describe the composition of pancreatic juice and explain the significance of pancreatic juice enzymes. 13. Identify the phases and explain the mechanisms of gastric regulation. 14. Explain the regulation of pancreatic juice and bile secretion. 15. Explain the significance of the enteric nervous system. 16. Describe the processes involved in the digestion and absorption of carbohydrates and proteins. 17. Describe the processes involved in the digestion, absorption, and transport of dietary lipids. Marc Imhotep Cray, M.D.
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Functions of the GI Tract Motility:
Movement of food through GI tract oIngestion: • Taking food into the mouth oMastication: • Chewing food and mixing it with saliva oDeglutition: • Swallowing food oPeristalsis: • Rhythmic wave-like contractions that move food through GI tract Marc Imhotep Cray, M.D.
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Functions of the GI Tract (2) Secretion: Includes both exocrine and endocrine secretions oExocrine: • HCl, H20, HC03-, bile, lipase, pepsin, amylase, trypsin, elastase, and histamine are secreted into lumen of GI tract oEndocrine: • Stomach and small intestine secrete hormones to help regulate GI system Gastrin, secretin, CCK, GIP, GLP-1, guanylin, VIP, and somatostatin Marc Imhotep Cray, M.D.
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Functions of the GI Tract (3) Digestion: Breakdown of food particles into subunits (chemical structure change) Absorption: Process of passage of digestion (chemical subunits) into blood or lymph Storage and elimination: • Temporary storage and elimination of indigestible food Marc Imhotep Cray, M.D.
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Digestive System (GI Tract): Gross Anatomical Arrangement GI tract divided into: Alimentary canal Accessory digestive organs
GI tract is 30 ft. long and extends from mouth to anus
Marc Imhotep Cray, M.D.
Fox SI. Human Physiology 12th ed. New York, NY: McGraw-Hill, 2011.
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Layers of GI Tract Composed of 4 tunics: • Mucosa • Submucosa • Muscularis • Serosa
Fox SI. Human Physiology 12th ed. New York, NY: McGraw-Hill, 2011. Marc Imhotep Cray, M.D.
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Mucosa Lines lumen of GI tract Consists of simple columnar epithelium o Lamina propria: • Thin layer of connective tissue containing lymph nodules o Muscularis mucosae: • Thin layer of smooth muscle responsible for folds Folds increase surface area for absorption
o Goblet cells: • Secrete mucus
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Submucosa Thick, highly vascular layer of connective tissue
Absorbed molecules enter blood and lymphatic vessels Submucosal plexus (Meissner’s plexus): Provide autonomic nerve supply to muscularis mucosae Marc Imhotep Cray, M.D.
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Muscularis Responsible for segmental contractions and peristaltic movement through GI tract Inner circular layer of smooth muscle Outer longitudinal layer of smooth muscle o Contractions of these layers move food through tract pulverize and mix food
Myenteric plexus located between 2 muscle layers Major nerve supply to GI tract o Fibers and ganglia from both sympathetic and parasympathetic nervous systems
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Serosa ď ą Binding and protective outer layer ď ą Consists of areolar connective tissue covered with simple squamous epithelium
Fox SI. Human Physiology 12th ed. New York, NY: McGraw-Hill, 2011. Marc Imhotep Cray, M.D.
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Regulation of GI Tract Extrinsic innervation: Parasympathetic nervous system (PNS): oVagus and spinal nerves (preganglionic fibers): • Stimulate motility and GI secretions
Sympathetic nervous system(SNS): oPostganglionic sympathetic fibers that pass through submucosal and myenteric plexuses and innervate GI tract: • Reduce peristalsis and secretory activity Marc Imhotep Cray, M.D.
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Regulation of the GI Tract (2) Enteric (Intrinsic) nervous system (ENS): Sites where parasympathetic fibers synapse with postganglionic neurons that innervate smooth muscle o Submucosal and myenteric plexuses: • Local regulation of GI tract
Paracrine secretion: Molecules acting locally
Hormonal secretion: Secreted by mucosa Marc Imhotep Cray, M.D.
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From Mouth to Stomach Mastication (chewing): Mixes food with saliva which contains salivary amylase oEnzyme that can catalyze partial digestion of starch
Deglutition (swallowing): Begins as a voluntary activity Involves 3 phases: oOral phase is voluntary oPharyngeal and esophageal phases are involuntary • Cannot be stopped Larynx is raised Epiglottis covers entrance to respiratory tract Marc Imhotep Cray, M.D.
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From Mouth to Stomach cont. Involuntary muscular contractions and relaxations in
mouth, pharynx, larynx, and esophagus are coordinated by swallowing center in medulla Esophagus: • Connects pharynx to stomach • Upper third contains skeletal muscle • Middle third contains a mixture of skeletal and smooth muscle • Terminal (lower third) portion contains only smooth muscle
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Esophagus Peristalsis: Produced by a series of localized reflexes in response to distention of wall by bolus oWave-like muscular contractions: • Circular smooth muscle contract behind, relaxes in front of bolus
• Followed by longitudinal contraction (shortening) of smooth muscle rate of 2-4 cm/sec • After food passes into stomach, LES constricts Marc Imhotep Cray, M.D.
Fox SI. Human Physiology 12th ed. New York, NY: McGraw-Hill, 2011.
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Stomach Most distensible part of GI tract empties into duodenum Functions of stomach: Stores food Initiates digestion of proteins Kills bacteria Moves food (chyme) into intestine Marc Imhotep Cray, M.D.
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Stomach cont. Contractions of stomach churn chyme Mix chyme w gastric secretions Push food into intestine
Fox SI. Human Physiology 12th ed. New York, NY: McGraw-Hill, 2011. Marc Imhotep Cray, M.D.
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Stomach cont. ď ąGastric mucosa has gastric pits in folds ď ą Cells that line folds deeper in mucosa are gastric glands
Fox SI. Human Physiology 12th ed. New York, NY: McGraw-Hill, 2011. Marc Imhotep Cray, M.D.
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Gastric Glands Secrete gastric juice: Goblet cells mucus Parietal cells HCl and intrinsic factor Chief cells pepsinogen Enterochromaffin-like cells (ECL) histamine and serotonin G cells gastrin D cells somatostatin Stomach ghrelin
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HCl Production Parietal cells secrete H+ into gastric lumen by primary active transport, through H+/ K+ ATPase pump Parietal cell’s basolateral membrane takes in Clagainst its electrochemical gradient, by coupling its transport with HC03Marc Imhotep Cray, M.D.
Fox SI. Human Physiology 12th ed. New York, NY: McGraw-Hill, 2011.
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HCl Production cont. HCl production is stimulated: Indirectly by gastrin Indirectly by Ach
ACh and gastrin stimulate release of histamine Histamine stimulates parietal cells to secrete HCl
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HCl Functions Makes gastric juice very acidic Denatures ingested proteins (alter tertiary structure) so become more digestible
Activates pepsinogen to pepsin Pepsin is more active at pH of 2.0
Fox SI. Human Physiology 12th ed. New York, NY: McGraw-Hill, 2011. Marc Imhotep Cray, M.D.
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Digestion and Absorption in Stomach Proteins partially digested by pepsin Carbohydrate digestion by salivary amylase is soon inactivated by acidity Alcohol and aspirin are only commonly ingested substances absorbed
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Gastric and Peptic Ulcers Peptic ulcers: • Erosions of mucous membranes of stomach or duodenum produced by action of HCl
Zollinger-Ellison syndrome: • Ulcers of duodenum are produced by excessive gastric acid secretions
Helicobacter pylori: • Bacterium that resides in GI tract that may produce ulcers
Acute gastritis: • Histamine released by tissue damage and inflammation stimulate further acid secretion Marc Imhotep Cray, M.D.
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Protective Mechanisms of Stomach Parietal and chief cells impermeable to HCl Alkaline mucus contains HC03Tight junctions between adjacent epithelial cells Rapid rate of cell division (entire epithelium replaced in 3 days) Prostaglandins inhibit gastric secretions Marc Imhotep Cray, M.D.
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Small Intestine Each villus is a fold in mucosa Covered w columnar epithelial cells interspersed w goblet cells Epithelial cells at tips of villi are exfoliated and replaced by mitosis in crypt of Lieberkuhn Lamina propria contain lymphocytes, capillaries, and central lacteal Marc Imhotep Cray, M.D.
Fox SI. Human Physiology 12th ed. New York, NY: McGraw-Hill, 2011.
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Absorption in Small Intestine Duodenum and jejunum: Carbohydrates, amino acids, lipids, iron, and Ca2+
Ileum: Bile salts, vitamin B12, electrolytes, and H20
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Intestinal Enzymes • Microvilli contain brush border enzymes that are not secreted into the lumen. • Brush border enzymes remain attached to the cell membrane with their active sites exposed to the chyme.
• Absorption requires both brush border enzymes and pancreatic enzymes.
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Intestinal Contractions and Motility 2 major types of contractions occur in small intestine: Peristalsis: o Slow movement o Pressure at pyloric end of small intestine is greater than at distal end Segmentation: o Major contractile activity of small intestine o Contraction of circular smooth muscle • Mix chyme Marc Imhotep Cray, M.D.
Insert fig. 18.14
Fox SI. Human Physiology 12th ed. New York, NY: McGraw-Hill, 2011.
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Contractions of Intestinal Smooth Muscles Occur automatically in response to endogenous pacemaker activity Rhythm of contractions is paced by graded depolarizations called slow waves Slow waves produced by interstitial cells of Cajal Slow waves spread from 1 smooth muscle cell to another through nexuses Fox SI. Human Physiology 12th ed. New York, NY: McGraw-Hill, 2011. Marc Imhotep Cray, M.D.
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Fox SI. Human Physiology 12th ed. New York, NY: McGraw-Hill, 2011.
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Contractions of Intestinal Smooth Muscles When slow waves rise above threshold triggers APs by opening of VG Ca2+ channels Inward flow of Ca2+: o Produces upward depolarization phase o Stimulates contraction of smooth muscle Repolarization: VG K+ channels open o Slow waves decrease in amplitude as they are conducted. May stimulate contraction in proportion to magnitude of depolarization Parasympathetic NS, stretch and gastrin increase amplitude of slow waves Stimulate APs SNS decrease APs Marc Imhotep Cray, M.D.
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Intestinal Smooth Muscle Action Potential +30
Vg Ca++ Channel
-55
Vg K+ Channel Fox SI. Human Physiology 12th ed. New York, NY: McGraw-Hill, 2011.
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Cells and Electrical Events in Muscularis
Fox SI. Human Physiology 12th ed. New York, NY: McGraw-Hill, 2011. Marc Imhotep Cray, M.D.
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Large Intestine Outer surface bulges outward to form haustra Little absorptive function o Absorbs H20, electrolytes, several vitamin B complexes, vitamin K, and folic acid • Intestinal microbiota produce significant amounts of folic acid and vitamin K • Bacteria ferment indigestible molecules to produce short-chain fatty acids • Does not contain villi
Secretes H20, via active transport of NaCl into intestinal lumen Guanylin stimulates secretion of Cl- and H20, and inhibits absorption of Na+ (minor pathway) o Membrane contains Na+/K+ pumps • Minor pathway Marc Imhotep Cray, M.D.
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Fluid and Electrolyte Absorption in Intestine Small intestine: Most of fluid and electrolytes are absorbed by small intestine Absorption of H20 occurs passively as a result of osmotic gradient created by active transport o Aldosterone stimulates NaCl and H20 absorption in ileum
Large intestine: Absorbs about 90% of remaining volume o Absorption of H20 occurs passively as a result of the osmotic gradient created by active transport of Na+ and Cl-
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Defecation Waste material passes to rectum Occurs when rectal pressure rises and external anal sphincter relaxes Defecation reflex: Longitudinal rectal muscles contract to increase rectal pressure o Relaxation of internal anal sphincter Excretion is aided by contractions of abdominal and pelvic skeletal muscles o Push feces from the rectum Marc Imhotep Cray, M.D.
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Structure of Liver
Liver largest internal organ Hepatocytes form hepatic plates that are 1–2 cells thick Arranged into functional units called lobules
Plates separated by sinusoids More permeable than other capillaries
Contains phagocytic Kupffer cells
Secretes bile into bile canaliculi which are drained by bile ducts Marc Imhotep Cray, M.D.
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Structure of Liver (2)
Insert fig. 18.20
Fox SI. Human Physiology 12th ed. New York, NY: McGraw-Hill, 2011. Marc Imhotep Cray, M.D.
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Hepatic Portal System Products of digestion that are absorbed are delivered to liver Capillaries drain into hepatic portal vein, which carries blood to liver ¾ blood is deoxygenated Hepatic vein drains liver
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Enterohepatic Circulation Compounds that recirculate
between liver and intestine Many compounds can be absorbed through small intestine and enter hepatic portal blood Variety of exogenous compounds are secreted by liver into bile ducts
Can excrete these compounds into intestine with bile Fox SI. Human Physiology 12th ed. New York, NY: McGraw-Hill, 2011. Marc Imhotep Cray, M.D.
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Major Categories of Liver Function
Fox SI. Human Physiology 12th ed. New York, NY: McGraw-Hill, 2011.
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Bile Production and Secretion Liver produces and secretes 250–1500 ml of bile/day Bile pigment (bilirubin) is produced in spleen, bone marrow, and liver Derivative of heme groups (without iron) from hemoglobin.
Free bilirubin combines with glucuronic acid and forms conjugated bilirubin Secreted into bile
Converted by bacteria in intestine to urobilinogen Urobilogen is absorbed by intestine and enters hepatic vein o Recycled, or filtered by kidneys and excreted in urine
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Metabolism of Heme and Bilirubin
Fox SI. Human Physiology 12th ed. New York, NY: McGraw-Hill, 2011. Marc Imhotep Cray, M.D.
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Bile Production and Secretion (2) Bile acids are derivatives of cholesterol Major pathway of cholesterol breakdown in body
Principal bile acids are: Cholic acid Chenodeoxycholic acid o Combine with glycine or taurine to form bile salts Bile salts aggregate as micelles
95% of bile acids are absorbed by ileum Fox SI. Human Physiology 12th ed. New York, NY: McGraw-Hill, 2011. Marc Imhotep Cray, M.D.
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Detoxification of Blood Liver can remove hormones, drugs, and other biologically active molecules from blood by: Excretion into the bile Phagocytosis by Kupffer cells Chemical alteration of the molecules oAmmonia is produced by deamination of amino acids in liver oLiver converts it into urea • Excreted in urine
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Detoxification of the Blood cont. Inactivation of steroid hormones and drugs Conjugation of steroid hormones and xenobiotics make them anionic oCan be transported into bile by multispecific organic anion transport carriers
Steroid and xenobiotic receptors stimulate production of cytochrome P450 enzymes
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Secretion of Glucose, Triglycerides and Ketones Liver helps regulate blood glucose concentration by: Glycogenesis and lipogenesis Glycogenolysis and gluconeogenesis
Contains enzymes required to convert free fatty acids into ketone bodies
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Production of Plasma Proteins Albumin and most of plasma globulins (except immunoglobulins) are produced by liver Albumin: Constitutes 70% of total plasma protein o Contributes most to colloid osmotic pressure in blood
Globulins: Transport cholesterol and hormones Inhibit trypsin Produce blood clotting factors I, II, III, V, VII, IX, XI Marc Imhotep Cray, M.D.
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Gallbladder Sac-like organ attached to inferior surface of liver Stores and concentrates bile When gallbladder fills with bile, it expands Contraction of muscularis layer of gallbladder ejects bile into common bile duct into duodenum
When small intestine is empty, sphincter of Oddi closes Bile is forced up to cystic duct to gallbladder Marc Imhotep Cray, M.D.
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Pancreas Exocrine: Acini: oSecrete pancreatic juice
Endocrine: Islets of Langerhans: oSecrete insulin and glucagon Fox SI. Human Physiology 12th ed. New York, NY: McGraw-Hill, 2011.
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Pancreatic Juice • Contains H20, HC03- and digestive enzymes
Fox SI. Human Physiology 12th ed. New York, NY: McGraw-Hill, 2011.
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Pancreatic Juice • Complete digestion of food requires action of both pancreatic and brush border enzymes. • Most pancreatic enzymes are produced as zymogens. • Trypsin (when activated by enterokinase) triggers the activation of other pancreatic enzymes.
• Pancreatic trypsin inhibitor attaches to trypsin. • Inhibits its activity in the pancreas. Marc Imhotep Cray, M.D.
Fox SI. Human Physiology 12th ed. New York, NY: McGraw-Hill, 2011.
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Neural and Endocrine Regulation ď ąNeural and endocrine mechanisms modify activity of GI system ď ąGI tract is both an endocrine gland, and a target for action of hormones
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Regulation of Gastric Function Gastric motility and secretion are automatic Waves of contraction are initiated spontaneously by pacesetter cells Extrinsic control of gastric function is divided into 3 phases: Cephalic phase Gastric phase Intestinal phase Marc Imhotep Cray, M.D.
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Cephalic Phase Stimulated by sight, smell, and taste of food Activation of vagus: Stimulates chief cells to secrete pepsinogen Directly stimulates G cells to secrete gastrin Directly stimulates ECL cells to secrete histamine Indirectly stimulates parietal cells to secrete HCl
Continues into 1st 30 min. of a meal
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Gastric Phase Arrival of food in stomach stimulates gastric phase Gastric secretion stimulated by: oDistension oChemical nature of chyme (amino acids and short polypeptides) • Stimulates G cells to secrete gastrin • Stimulates chief cells to secrete pepsinogen • Stimulates ECL cells to secrete histamine Histamine stimulates secretion of HCl
oPositive feedback effect • As more HCl and pepsinogen are secreted, more polypeptides and amino acids are released Marc Imhotep Cray, M.D.
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Gastric Phase cont. Secretion of HCl is also regulated by a negative feedback effect: HCl secretion decreases if pH < 2.5 At pH of 1.0, gastrin secretion ceases o D cells stimulate secretion of somatostatin Paracrine regulator to inhibit secretion of gastrin
Marc Imhotep Cray, M.D.
Fox SI. Human Physiology 12th ed. New York, NY: McGraw-Hill, 2011.
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Intestinal Phase Inhibits gastric activity when chyme enters small intestine Arrival of chyme increases osmolality and distension Activates sensory neurons of vagus and produces an inhibitory neural reflex:
oInhibits gastric motility and secretion oIn presence of fat, enterogasterone inhibits gastric motility and secretion
Hormone secretion:
Inhibit gastric activity: oSomatostatin, CCK, and GLP-1
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Enteric Nervous System ď ąSubmucosal and myenteric plexuses contain 100 million neurons ď ąInclude preganglionic parasympathetic axons, ganglion cell bodies, postganglionic sympathetic axons; and afferent intrinsic and extrinsic sensory neurons
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Enteric Nervous System cont. Peristalsis: ď&#x201A;§ ACh and substance P stimulate smooth muscle contraction above bolus ď&#x201A;§ NO, VIP, and ATP stimulate smooth muscle relaxation below bolus
Fox SI. Human Physiology 12th ed. New York, NY: McGraw-Hill, 2011. Marc Imhotep Cray, M.D.
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Paracrine Regulators of Intestine Serotonin (5-HT): Stimulates intrinsic afferents, which send impulses into intrinsic nervous system; and activates motor neurons
Motilin: Stimulates contraction of duodenum and stomach antrum.
Guanylin: Activates guanylate cyclase, stimulating production of cGMP o cGMP stimulates intestinal cells to secrete Cl- and H20 • Inhibits the absorption of Na+
Uroguanylin: May stimulate kidneys to secrete salt in urine. Marc Imhotep Cray, M.D.
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Intestinal Reflexes Intrinsic and extrinsic regulation controlled by intrinsic and paracrine regulators Gastroileal reflex: Increased gastric activity causes increased motility of ileum and movement of chyme through ileocecal sphincter
Ileogastric reflex: Distension of ileum, decreases gastric motility
Intestino-intestinal reflex: Overdistension in 1 segment, causes relaxation throughout rest of intestine Marc Imhotep Cray, M.D.
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Secretion of Pancreatic Juice Secretion of pancreatic juice and bile is stimulated by: Secretin: o Occurs in response to duodenal pH < 4.5 o Stimulates production of HC03- by pancreas o Stimulates the liver to secrete HC03- into the bile
CCK:
o Occurs in response to fat and protein content of chyme in duodenum o Stimulates production of pancreatic enzymes o Enhances secretin o Stimulates contraction of sphincter of Oddi
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Digestion and Absorption of Carbohydrates Salivary amylase: Begins starch digestion
Pancreatic amylase: Digests starch to oligosaccharides Oligosaccharides hydrolyzed by brush border enzymes
Glucose is transported by secondary active transport with Na+ into the capillaries
Fox SI. Human Physiology 12th ed. New York, NY: McGraw-Hill, 2011. Marc Imhotep Cray, M.D.
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Digestion and Absorption of Protein Digestion begins in stomach when pepsin digests proteins to form polypeptides In duodenum and jejunum: Endopeptidases cleave peptide bonds in interior of polypeptide: o Trypsin o Chymotrypsin o Elastase
Exopeptidases cleave peptide bonds from the ends of the polypeptide: o Carboxypeptidase o Aminopeptidase Marc Imhotep Cray, M.D.
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Digestion and Absorption of Protein cont. Free amino acids absorbed by cotransport with Na+ Dipeptides and tripeptides transported by secondary active transport using a H+ gradient to transport them into cytoplasm Hydrolyzed into free amino acids and then secreted into blood Fox SI. Human Physiology 12th ed. New York, NY: McGraw-Hill, 2011. Marc Imhotep Cray, M.D.
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Digestion and Absorption of Lipids Arrival of lipids in duodenum serves as a stimulus for secretion of bile Emulsification: Bile salt micelles are secreted into duodenum to break up fat droplets
Pancreatic lipase and colipase hydrolyze triglycerides to free fatty acids and monoglycerides Colipase coats the emulsification droplets and anchors lipase enzyme to them Form micelles and move to brush border Marc Imhotep Cray, M.D.
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Digestion and Absorption of Lipids cont. Free fatty acids, monoglycerides, and lysolecithin leave micelles and enter into epithelial cells Resynthesize triglycerides and phospholipids within cell oCombine with a protein to form chylomicrons.
Secreted into central lacteals
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Transport of Lipids In blood, lipoprotein lipase hydrolyzes triglycerides to free fatty acids and glycerol for use in cells Remnants containing cholesterol are taken to the liver Form VLDLs which take triglycerides to cells Once triglycerides are removed, VLDLs are converted to LDLs oLDLs transport cholesterol to organs and blood vessels
HDLs transport excess cholesterol back to liver Marc Imhotep Cray, M.D.
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Absorption of Fat
Fox SI. Human Physiology 12th ed. New York, NY: McGraw-Hill, 2011.
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THE END
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