Slide 1Slide 2Slide 3Slide 4Slide 5Slide 6Slide 7Slide 8Slide 9Slide 10Slide 11Slide 12Slide 13Slide 14Slide 15Slide 16Slide 17Slide 18Slide 19Slide 20Slide 21Slide 22Slide 23Slide 24Slide 25Slide 26Slide 27Slide 28Slide 29Slide 30Slide 31Slide 32Slide 33Slide 34Slide 35Slide 36Slide 37Slide 38Slide 39Slide 40Slide 41Slide 42Slide 43Slide 44Slide 45Slide 46Slide 47Slide 48Slide 49Slide 50Slide 51Slide 52Slide 53Slide 54Slide 55Slide 56Slide 57Slide 58Slide 59Slide 60Slide 61Slide 62Slide 63Slide 64Ted Kalogeris, Ph.D.Office: M561, School of MedicinePhone: 884-8160 or 882-1030email: [email protected]•Digestion & Absorption•Metabolism & Energy Balance•Endocrine Control of Growth & Metabolism•Integrative Physiology: Exercise•Immune system•Reproduction & DevelopmentMajor take-home messages are listed in ITALICSFunctions of the gastrointestinal system [Silverthorn, Ch. 21]•Processing of ingested food & delivery of nutrients•Development: gut endoderm plays role in formation of heart, and is foundation for development of gut-derived organs: thyroid, lungs, liver, pancreas•Largest immune organ•Largest single habitat for microflora—bacteria, archaea, fungi 1014 organismsDigestive System[GI tract + accessory organs]•Gastrointestinal Tract mouth esophagus stomach small intestine large intestine rectum, anus•“Accessory” Organs salivary glands liver/gallbladder pancreas[Fig 21.3b, p. 700]Stomach [Fig. 21.3c, p. 700]Small intestine—duodenum, jejunum, ileum•Most digestion occurs in s.i.– carried out by pancreatic, intestinal enzymes, aided by other factors from liver via the gallbladder—all exocrine secretions enter at the duodenumLarge intestine—cecum, colon  rectum  anus•Reabsorption of water, electrolytes, bile acids•Absorption of some nutrients (vitamin K, short chain fatty acids•Forms semi-solid feces for elimination•Major habitat for resident microfloraSingle layer of epithelialcells—enterocytes, endocrinecells, goblet cellsLamina propria—hydrated, connectivetissue matrix which supports epithelium,contains capillaries, is collection point for lymph, contains sensory nerves,and immune cells Muscularis mucosae--thin layerof smooth muscle which controls movement of villi, contains efferent nerve endings from the submucosalplexus of the ENSMucosaFour layers in GI tract wall– Ch. 21, pp. 702-3SubmucosaConnective tissue layer containing larger blood vessels,lymph ducts, and the submucosal plexus (Meissner’s plexus)of nerves from the enteric nervous system (ENS)Muscularis externaInner layer of circular muscle—affects lumen diameterOuter layer of longitudinal muscle—affects lengthMyenteric plexus (Auerbach’s plexus)—lies between muscle layers,controls gut motility via coordination of contraction/relaxation ofthe two muscle layersSerosa•Outer covering—connective tissue membrane continuous with peritoneal membraneIntestinal Epithelium—specialized for absorption/transportNote: luminalsurface of colonlacks villiSee Fig. 21.7, p.710Intestinal epithelium is continually being renewed•Stem cell niche resides 4-5 cells from bottom of crypt•Two types of stem cells: 1) slowly dividing (stem cell renewal); 2) rapidly dividing (epithelial replacement)•Continuous proliferation pushes cells up the villus•As they migrate, they differentiate into enterocytes, enteroendocrine cells, goblet cells; transit time to villus tip = 3-5 days•On reaching tip, cells are shed, die (anoikis), and are replaced•Another population of proliferating cells moves downward from the stem cell niche to bottom of crypt  paneth cells (live for ~ 20 days, then phagocytosed and replaced)Intestinal epithelial cells are structurally and functionally polarized[Review section on epithelia, Ch. 3, pp. 80-84, Fig. 3.10e (p. 83)]Epithelial cells are polarized—different functions of apical vs basolateral sides determined by expression of different proteinsNa+ GlucoseNa/glucosetransporterK+ Na+Na/K ATPaseEnteric Nervous System (ENS)•Intrinsic nervous system, able to generate reflexes independently of CNS input—if cut neural connections to CNS, gut can still engage in regulated function— gut is only organ with such a system•However, CNS and gut communicate via afferent/efferent connections to ENS, + direct innervation to gut sensory/effector neurons[Ch. 21, pp. 716-17]Gastrointestinal Hormones [review key features of hormones, Ch. 7, pp. 208-9]•Synthesized and released from endocrine cells in gastric/intestinal epithelium in response to lumenal contents and/or neural signals—3 major ones: gastrin, CCK, secretin [Ch. 21, pp. 718-19]•Act to control gut functions so as to optimize digestionExample: CCKLumenal fat, aa’sM cellsCCK↑ Gallbladdercontraction↑ Pancreatic exocrine secretion↓GastricemptyingRole: 1) moves food aborally from mouthanus 2) mixes food with digestive secretions 3) breaks food into small particles, ↑ surface area•controlled by neural, hormonal, paracrine signals acting on GI smooth muscle•gastrointestinal smooth muscle contracts as a unit due to anatomic and electrical coupling.MOTILITY 1. Migrating myoelectric motor complex: slowly moving peristaltic wave progressing from stomach  colon/rectum—occurs during postabsorptive period, serves to clear the upper tract2. Peristalsis: aboral movement by progressive, simultaneous muscular contraction behind bolus and relaxation ahead of it. 2. Segmentation: mixing function--segments of gut alternately contracting and relaxingmixing of contents, but no net forward movement [Ch. 21, pp. 703-5]Two types: a) primary—initiated in esophagus by swallowing b) secondary—initiated by distension (local ENS reflexes)Peristalsis—moves material aborallySegmentation: mixes chymeSECRETION •78% of fluid passing through GI tract is secreted•Half from accessory organs, half from digestive tract epithelium•Mostly water & ions [Na+, K+, Cl-, HCO3-, H+]•Secreted ions are reabs- orbed, water follows osmotic gradients created by solute transfer[Ch. 21, pp. 705-9]HCl secretion from parietal cell in stomach—active pumping of H+followed by passive movement of Cl-, and accompanied by netmovement of HCO3- into the blood “alkaline tide” 123SECRETION (2)[pp. 705-6, Fig. 21.5a]Intestinal/pancreatic secretion of Cl- and