Presentation on theme: "Homework 1 Innervation of the stomach Sympathetic nerve?"— Presentation transcript:
1 Homework 1Innervation of the stomachSympathetic nerve?
2 A, Parasympathetic. Dashed lines indicate the cholinergic innervation of striated muscle in the esophagus and external anal sphincter. Solid lines indicate the afferent and preganglionic efferent innervation of the rest of the gastrointestinal tract.B, Sympathetic. Solid lines denote the afferent and preganglionic efferent connections between the spinal cord and the prevertebral ganglia. Dashed lines indicate the afferent and postganglionic efferent innervation.CG, celiac ganglion; IMG, inferior mesenteric ganglion; SMG, superior mesenteric ganglion.Gastrointestinal Physiology, Seventh Edition. LEONARD R. JOHNSON. 2007, Mosby, Inc.
3 Homework 2 Ionic mechanism of spike potential (Action potential): Depolarization: Ca2+ influx?L-type Ca2+ currentL-type Ca2+ channels provide the Ca2+ influx that initiates contraction. Blockade of Ca2+ channels reduces the duration and amplitude of electrical slow waves in many muscles and blocks generation of action potentials.Horowitz B, Ward SM, Sanders KM. Annu Rev Physiol. 1999;61:19-43.
4 Gastrointestinal Physiology (Part 2) Xia Qiang, PhDDepartment of PhysiologyZhejiang University School of Medicine
11 Secretion of bicarbonate ions Secreted by the epithelial cells of the ductules and ducts that lead from aciniUp to 145mmol/L in pancreatic juice (5 times that in the plasma)Neutralizing acid entering the duodenum from the stomach
14 OTHERS Trypsin inhibitor Blockade of trypsin activity Lithostathine Possible prevention of stone formation; constituent of protein plugsGP2Endocytosis?; formation of protein plugsPancreatitis-associated proteinBacteriostasis?Na , Cl , H2OHydration of secretionsCa?
19 Trypsin InhibitorInhibits the activity of trypsin and thus guards against the possible activation of trypsin and the subsequent autodigestion of the pancreas
20 Regulation of pancreatic secretion Basic stimuli that cause pancreatic secretionAchCholecystokinin:Secreted by I cellsStimulates the acinar cells to secrete large amounts of enzymesSecretin:Released by S cellsActs primarily on the duct cells to stimulate the secretion of a large volume of solution with a high HCO3- concentration
21 Stimulation of protein secretion from the pancreatic acinar cell Stimulation of protein secretion from the pancreatic acinar cell. A, The pancreatic acinar cell has at least two pathways for stimulating the insertion of zymogen granules and thus releasing digestive enzymes. ACh and CCK both activate Gα , which stimulates PLC, which ultimately leads to the activation of PKC and the release of Ca . Elevated [Ca ] also activates calmodulin (CaM), which can activate protein kinases (PK) and phosphatases (PP). Finally, VIP and secretin both activate Gα , which stimulates adenylyl cyclase (AC), leading to the production of cAMP and the activation of PKA. B, Applying a physiological dose of CCK (i.e., 10 pM) triggers a series of [Ca ] oscillations, as measured by a fluorescent dye. However, applying a supraphysiological concentration of CCK (1 nM) elicits a single large [Ca ] spike and halts the oscillations. Recall that high levels of CCK also are less effective in causing amylase secretion.
22 In addition to protein, acinar cells in the pancreas secrete an isotonic, plasma-like fluid. Stimulation of isotonic NaCl secretion by the pancreatic acinar cell. Both ACh and CCK stimulate NaCl secretion, probably through phosphorylation of basolateral and apical ion channels.The rise in [Cl ] produced by basolateral Cl uptake drives the secretion of Cl down its electrochemical gradient through channels in the apical membrane. As the transepithelial voltage becomes more lumen negative, Na moves through the cation-selective paracellular pathway (i.e., tight junctions) to join the Cl secreted into the lumen. Water also moves through this paracellular pathway, as well as through aquaporin water channels on the apical and basolateral membranes. Therefore, the net effect of these acinar cell transport processes is the production of an isotonic, NaCl-rich fluid that accounts for ∼25% of total pancreatic fluid secretion.
27 Regulation of pancreatic secretion Phases of pancreatic secretion: A meal triggers cephalic, gastric, and intestinal phases of pancreatic secretionCephalic PhaseGastric PhaseIntestinal Phase
28 The three phases of pancreatic secretion StimulantRegulatory PathwayPercentage of Maximum Enzyme SecretionCephalicSightSmellTasteMasticationVagal pathways25%GastricDistentionGastrin?Vagal-cholinergic10%-20%IntestinalAmino acidsFatty acidsH+CholecystokininSecretinEnteropancreatic reflexes50%-80%
29 Three phases of pancreatic secretion Three phases of pancreatic secretion. A, During the cephalic phase, the sight, taste, or smell of food stimulates pancreatic acinar cells, through the vagus nerve and muscarinic cholinergic receptors, to release digestive enzymes and, to a lesser extent, stimulates duct cells to secrete HCO and fluid. The release of gastrin from G cells is not important during this phase. During the gastric phase, the presence of food in the stomach stimulates pancreatic secretions'primarily from the acinar cells'through two routes. First, distention of the stomach activates a vagovagal reflex. Second, protein digestion products (peptones) stimulate G cells in the antrum of the stomach to release gastrin, which is a poor agonist of the CCK receptors on acinar cells. B, The arrival of gastric acid in the duodenum stimulates S cells to release secretin, which stimulates duct cells to secrete HCO and fluid. Protein and lipid breakdown products have two effects. First, they stimulate I cells to release CCK, which causes acinar cells to release digestive enzymes. Second, they stimulate afferent pathways that initiate a vagovagal reflex that primarily stimulates the acinar cells through M cholinergic receptors.
30 Mechanisms that protect the acinar cell from autodigestion Protective FactorMechanismPackaging of many digestive proteins as zymogensPrecursor proteins lack enzymatic activitySelective sorting of secretory proteins and storage in zymogen granulesRestricts the interaction of secretory proteins with other cellular compartmentsProtease inhibitors in the zymogen granuleBlock the action of prematurely activated enzymesCondensation of secretory proteins at low pHLimits the activity of active enzymesNondigestive proteasesDegrade active enzymes
32 Acute pancreatitisAcute pancreatitis is sudden swelling and inflammation of the pancreasThe symptomatology and complications of acute pancreatitis are caused by autodigestion (resulting from the leakage of pancreatic enzymes) of the pancreas and surrounding tissueIt is commonly due to biliary tract disease, complications of heavy alcohol use, or idiopathic causesMortality rates range from below 10% to more than 50%, depending on severity
39 JaundiceJaundice is the most visible manifestation of an underlying hepatic and/or biliary tract disease.This is a yellow discoloration of the skin, sclerae, and mucous membranes that occurs secondary to elevated serum bilirubin in adults.Jaundice is usually not clinically apparent until the serum bilirubin concentration is >2.5mg/dL.
40 Functions of bile Emulsifying or detergent function of bile salts Bile salts help in the absorption of:Fatty acidMonoglyceridesCholesterolOther lipids
41 Emulsifying large fat particles to facilitate its digestion
47 Regulation of bile secretion Substances increasing bile productionBile salts (Enterohepatic circulation of the bile)Secretin: stimulating H2O and HCO3- secretion from the duct cellsSubstance inhibiting bile productionSomatostatin
48 Contraction of the gall bladder Substances causing gall bladder contractionAChCCKGastrin
51 Secretin and cholecystokinin are produced and secreted by cells in the lining of the alimentary tract. Which of the following statements about these 2 secretions is true?A They are produced by enteroendocrine cells in the lining of the stomachB They are digestive enzymes present within the lumen of the duodenumC They are produced by Paneth cellsD They are hormones whose target cells are primarily in the pancreas and biliary tractE They are produced by Brunner’s glands and released into the lumina of the crypts of Lieberkühn
52 Liver bile flow is increased by: A Gastrin.B Pancreatic secretion.C Vagal stimulation.D Sympathetic nerve stimulation
54 Small intestinal juices Secreted by:Brunners glandsCrypts of Lieberkuhn1~3 L/daypH 7.6IsosmoticComponentsH2OElectrolytes (Na+, K+, Ca2+, Cl-)MucusIgAEnterokinase
55 Small intestinal juices Function: Completing the digestion of peptides, carbohydrates & fatSecretion by intestinal glands is mainly due to the local effects of chyme in the intestine and is regulated by both neural and hormonal factors
56 Movement of small intestine during digestion Tonic contraction: maintaining a basal state of intestinal smooth muscle contractionSegmentation: consisting of the alternate contraction and relaxation of adjacent bands of circular smooth musclePeristalsis: a ring of muscle contraction appears on the oral side of a bolus of ingesta and moves toward the anus, propelling the contents of the lumen in that direction; as the ring moves, the muscle on the other side of the distended area relaxes, facilitating smooth passage of the bolus
58 Migrating motor complex (MMC) Local areas of peristaltic contractionPresent in the interdigestive period and disappear when feeding beginsSweeping material (undigested food residues, dead mucosal cells, bacteria) into the colon and keeping the small intestine cleanRegulated by autonomic nerves and by the release of motilin
59 Contractions at three loci in the small bowel Contractions at three loci in the small bowel. Note that at each locus, phases of no or intermittent contractions are followed by a phase of continuous contractions that ends abruptly. Also note that the phase of continuous contractions appears to migrate aborally along the bowel. Such a pattern is called the migrating motor complex (MMC). min, minute; mm Hg, millimeters of mercury
60 Regulation of intestinal motility Autoregulation: Regulated by BERNeural Reflexes:mainly by ‘short’ reflexes in the intrinsic plexuses which are responsible for peristalsis and segmentationalso by extrinsic nerves (sympathetic & vagal nerves) which mediate ‘long’ reflexesHormonal control:Gastrin, CCK, motilin, 5-HT (+)Secretin, VIP, glucagon (-)
62 Function of large intestine The principle functions of the colon:Absorption of water and electrolytes from the chyme to form solid fecesStorage of fecal matter until it can be expelledDigestion in large intestine: very limitedBacteria: vitamin B, K
63 Motility of the colon Haustration: mixing movement Mass movement: propulsive movementSegmentation
65 Two mass movements. A, Appearance of the colon before the entry of barium sulfate. B, As the barium enters from the ileum, it is acted on by haustral contractions. C, As more barium enters, a portion is swept into and through an area of the colon that has lost its haustral markings. D, The barium is acted on by the returning haustral contractions. E, A second mass movement propels the barium into and through areas of the transverse and descending colon. F, Haustrations again return. This type of contraction accomplishes most of the movement of feces through the colon
69 Major gastrointestinal diseases and nutritional deficiencies Organ Site of Predominant DiseaseDefects in Nutrient Digestion/AbsorptionCeliac sprueDuodenum and jejunumFat absorption, lactose hydrolysisChronic pancreatitisExocrine pancreasFat digestionSurgical resection of ileum; Crohn disease of ileumIleumCobalamin and bile acid absorptionPrimary lactase deficiencySmall intestineLactose hydrolysis
70 CarbohydratesThe three monosaccharide products of carbohydrate digestion— glucose, galactose, and fructose—are absorbed by the small intestine in a two-step process involving their uptake across the apical membrane into the epithelial cell and their coordinated exit across the basolateral membrane.The Na/glucose transporter 1 (SGLT1) is the membrane protein responsible for glucose and galactose uptake at the apical membrane. The exit of all three monosaccharides across the basolateral membrane uses a facilitated sugar transporter (GLUT2).
71 ProteinsAction of luminal, brush border, and cytosolic peptidases. Pepsin from the stomach and the five pancreatic proteases hydrolyze proteins—both dietary and endogenous—to single amino acids, AA, or to oligopeptides, (AA) . These reactions occur in the lumen of the stomach or small intestine. Various peptidases at the brush borders of enterocytes then progressively hydrolyze oligopeptides to amino acids. The amino acids are directly taken up by any of several transporters. The enterocyte directly absorbs some of the small oligopeptides through the action of the H /oligopeptide cotransporter (PepT1). These small peptides are digested to amino acids by peptidases in the cytoplasm of the enterocyte. Several Na -independent amino acid transporters move amino acids out of the cell across the basolateral membrane
72 Absorption of whole proteins Absorption of whole proteins. Both enterocytes and specialized M cells can take up intact proteins. The more abundant enterocytes can endocytose far more total protein than can the M cells. However, the lysosomal proteases in the enterocytes degrade ∼90% of this endocytosed protein. The less abundant M cells take up relatively little intact protein, but approximately half of this emerges intact at the basolateral membrane. There, immunocompetent cells process the target antigens and then transfer them to lymphocytes, thus initiating an immune response
73 LipidsThe breakdown of emulsion droplets to mixed micelles
74 Micellar transport of lipid breakdown products to the surface of the enterocyte. Mixed micelles carry lipids through the acidic unstirred layer to the surface of the enterocyte. 2-MAG, fatty acids, lysophospholipids, and cholesterol leave the mixed micelle and enter an acidic microenvironment created by an apical Na-H exchanger. The acidity favors the protonation of the fatty acids. The lipids enter the enterocyte by (1) nonionic diffusion, (2) incorporation into the enterocyte membrane (collision), or (3) carrier-mediated transport.
75 Re-esterification of digested lipids by the enterocyte and the formation and secretion of chylomicrons. The enterocyte takes up short- and medium-chain fatty acids and glycerol and passes them unchanged into the blood capillaries. The enterocyte also takes up long-chain fatty acids and 2-MAG and resynthesizes them into TAG in the SER. The enterocyte also processes cholesterol into cholesteryl esters and lysolecithin into lecithin. The fate of these substances, and the formation of chylomicrons, is illustrated by steps 1 to 8.
76 CalciumActive Ca uptake in the duodenum. The small intestine absorbs Ca by two mechanisms. The passive, paracellular absorption of Ca occurs throughout the small intestine. This pathway predominates, but it is not under the control of vitamin D. The second mechanism—the active, transcellular absorption of Ca —occurs only in the duodenum. Ca enters the cell across the apical membrane through a channel. Inside the cell, the Ca is buffered by binding proteins, such as calbindin, and is also taken up into intracellular organelles, such as the endoplasmic reticulum
77 IronAbsorption of nonheme and heme iron in the duodenum. The absorption of nonheme iron occurs almost exclusively as Fe , which crosses the duodenal apical membrane through DMT1, driven by a H gradient, which is maintained by Na-H exchange. Heme enters the enterocyte by an unknown mechanism. Inside the cell, heme oxygenase releases Fe , which is then reduced to Fe . Cytoplasmic Fe then binds to mobilferrin for transit across the cell to the basolateral membrane. Fe probably exits the enterocyte through basolateral ferroportin. The ferroxidase activity of hephaestin converts Fe to Fe for carriage in the blood plasma bound to transferrin.
78 Summary General properties of GI Stomach Pancrea Small and large intestineAbsorption