DIGESTIVEPHYSIOLOGY
PhysiologyUnit4
InPhysiologyToday
Functions
• Motility– Ingestion– Mastication– Deglutition– Peristalsis
• Secretion– 7liters/day!– Exocrine/endocrine
• Digestion• Absorption
DigestionofCarbohydrates
• Averageintakeis250-300g/day
• Amylase• Salivary,pancreatic• Products:maltose,shortchainsofglucose
• Brushborderenzymes• Products:glucose,galactose,fructose
AbsorptionofCarbohydrates• Luminalabsorption• Glucose• cotransportwithNa+intoenterocytes
• Basolateralabsorption• Monosaccharidesenterbloodvia facilitateddiffusion
DigestionofProteins• Require40-50gofprotein/day
– Supplyessentialaminoacids– Weconsume70-90g/day
• Stomach– Pepsin
• Productsareshortchainpolypeptides• Smallintestinesfrompancreas• Trypsin,chymotrypsin
• Productsareshortchainpolypeptides• Carboxypeptidase
• Productsarefreeaminoacids• SmallIntestinesfrombrushborderenzymes• Aminopeptidase
• Productsarefreeaminoacids
AbsorptionofProteins
• Luminalabsorption– Freeaminoacidsenterenterocytesbycounter-transportwithNa+
– Shortpolypeptides(2or3aminoacids)enterenterocytesby counter-transportofH+
• Basolateralabsorption– Freeaminoacidsenterbloodbyfacilitateddiffusion
DigestionofFat
• Dailyintake70-100g/day(mostlytriglycerides)
• Emulsificationbybilesalts• Pancreaticlipase– Monoglyceride+2fattyacids
• Formationofmicellesbybilesalts
AbsorptionofFat• LuminalAbsorption– Monoglyceridesandfattyacidsenterenterocytesbydiffusion
• Basolateralabsorptionintolacteals– Exocytosisofchylomicrons
– Chylomicronscontaintriglycerides,phospholipids,cholesterol,fat-solublevitamins
LipidTransport
• Fromlymphaticstothoracicduct• Freefattyacidsandglycerolintotissues• Leftoverstoliver– Remnantparticlescontaincholesterol– Combinedwithapoproteins(lipidbindingprotein)toproduceVLDL’s– Delivertriglyceridestootherorgans
Lipoproteins• Lipid&proteincomplexes– Transportcholesterol&triglyceridesinblood– Proteinallowshydrophobiclipidstoremaininsuspension
• Fiveclasses:Basedondensity,molecularweight,size,chemicalcomposition
• Chylomicrons• VLDL• IDL• LDL
– HighlevelsassociatedwithincreasedriskCVD• HDL
– LowlevelsassociatedwithincreasedriskofCVD– Bestprofile=highHDL,lowLDL
AbsorptionofVitamins
• Fat-solublevitamins– VitaminsA,D,E,K– Exocytosisinchylomicrons
• Water-solublevitamins– VitaminsB,C– Absorbedbydiffusion ormediatedtransport
• VitaminB12– Bindstointrinsicfactor– Endocytosis (inileum)intoenterocytes
VitaminB12
AbsorptionofWaterandMinerals
• Waterismostabundantsubstanceinchyme– 8Lofingestedandsecretedwaterenterthesmallintestineeachday!
– 1.5Lmakeittothelargeintestine– 80%absorbedinsmallintestine
• Minerals– Na+
– HCO3-
– Cl-
– SmallconcentrationsK+,Mg2+,Ca2+,Fe3+,Zn2+,I-
RegulationofGastrointestinalProcesses
• Regulationoftheconditionsofthelumenofthetract(theoutsideofthebody)
• Governedbythevolumeandcompositionoftheluminalcontentsratherthanthenutritionalstateofthebody(theinsideofthebody)
BasicPrinciples
1. Distentionofthelumenwall(volumeofcontents)
2. Chymeosmolarity(soluteconcentration)3. Chymeacidity4. Chymeconcentrations–Monosaccharides– Fattyacids– Peptides– Aminoacids
NeuralRegulation
• EntericNervousSystem(ENS)
• Myentericplexus– Influencessmoothmuscleactivity
• Submucosalplexus– Influencessecretoryactivity
NeuralRegulation
• Neuralactivityinoneplexusinfluencestheactivityoftheother
• Stimulationatonepointintheplexuscanleadtoimpulsesthatareconductedbothupanddownthetract
• NeuralreflexesindependentofCNS• CNScaninfluencemotilityandsecretionofthetract
HormonalRegulation
• HormonesthatcontroltheGIsystemaresecretedbycellsscatteredthroughouttheepitheliumofthestomachandsmallintestine
• Onesurfaceofeachendocrinecellisexposedtothelumenofthetract
• Chemicalsinchymestimulatethecelltosecreteitshormonesfromtheoppositesideofthecellintotheblood
HormonalRegulations
• Eachhormoneparticipatesinafeedbackcontrolsystemthatregulatessomeaspectofthetheluminalenvironment
• MostGIhormonesaffectmorethanonetypeoftargetcell
• BestunderstoodpeptideGIHormones– Gastrin– Cholecystokinin(CCK)– Secretin– Glucose-dependentinsulinotropicpeptide(GIP)
Gastrin
• Endocrinecelllocation:– Gcellsoftheantrumofstomach
• Stimulusforrelease– Proteininstomach– Parasympatheticnervoussystem
• Actions– Stimulates• Stomach:(+)acidsecretionandmotility• Pancreas:(+)enzymesecretions• Intestines:(+)motilityinileumandcolon
Cholecystokinin(CCK)
• Endocrinecelllocation:smallintestine• Stimulusforrelease– aminoacids,fattyacidsinsmallintestine
• Actions– Stimulates
• Pancreas:(+)enzymesecretion• Gallbladder:(+)contraction
– Potentiates• Pancreas:(+)bicarbonatesecretion• Liver:(+)bicarbonatesecretion
– Inhibits• Stomach:(-)acidsecretion,gastricmotility
Secretin
• Endocrinecelllocation:smallintestine• Stimulusforrelease– Acidinsmallintestine
• Actions• Stimulates• Pancreas:(+)bicarbonatesecretion• Liver:(+)bicarbonatesecretion
• Inhibits• Stomach:acidsecretion,gastricmotility
Glucose-DependentInsulinotropicPeptide
• Endocrinecelllocation:smallintestine• Stimulusforrelease– glucose,fatinthesmallintestine
• Actions– Stimulates• Pancreas:(+)insulinsecretion
Stomach
• Function– Initiatesproteindigestion
– Killsbacteria– Intrinsicfactor
• Secretedbyparietalcells• NeededforVitaminB12absorptioninileum
– Absorption• Water• Alcohol• Aspirin
• 3functionsofpHinstomach– Denatureingestedprotein
– Convertpepsinogentopepsin• Digestsproteins
– Destroybacteria
GastricGlands• Gobletcells
– mucus• Parietalcells
– HCl– Intrinsicfactor
• Chiefcells– Pepsinogen
• Argentaffincells– Serotonin– Regulateintestinal
movements• Gcells
– Gastrin
Pancreas• Pancreaticacini– Pancreaticjuice
• water• bicarbonate• digestiveenzymes
– Activationbyenterokinase
PancreaticEnzymes
EnergyRegulationbyIsletsofLangerhans
• Threecelltypesproducepeptidehormones– Betacells:insulin
• Stimulatescellularuptakeofglucose• Inliver,activatesglycogenesis• Stimulateslipidsynthesis• Stimulatescellularuptakeofaminoacids
– Alphacells:glucagon• Encouragesliberationofreserves• Preventsglucoseuptakebyliver,muscle,adipose
– Deltacells:somatostatin• Notsure
RegulationofInsulinandGlucagonSecretion
• Effectsofglucoseandaminoacids– Increaseinplasmaglucose
• Stimulatesbcells• Inhibitsacells
– Decreaseinplasmaglucose• decreasedinsulinproduction• increasedglucagonproduction
– Mealshighinprotein• stimulatesinsulin
– Mealshighinproteinandlowincarbohydrate• stimulatesglucagon• result:increaseinbloodglucoseandincreasedincorporationofaminoacidsintotissues
RegulationofInsulinandGlucagonSecretion
• Effectsofautonomicnerves– Parasympatheticactivation• increasedinsulin
– Sympatheticactivation• increasedglucagon,inhibitsinsulin
– Goal: Keepbloodglucosebetween– 50-170mg/100ml• higher=glycosilation;lower=braindamage
FunctionsoftheLiver
• Exocrine• Endocrine• Clottingfunctions• Synthesizesplasmaproteins• Organicmetabolism• Cholesterolmetabolism• Excretoryanddegradativefunctions
Exocrine&EndocrineFunctions
ExocrineFunctions• Synthesisandsecretionof
bilesalts– 250-1500ml/day
• Addsbicarbonaterichsolutiontobile
EndocrineFunctions• SecretesIGF-1
– promotescelldivision
• FormsT3 fromT4• Secretesangiotensinogen
– IncreasesBP– Stimulatesaldosterone
secretion
• Metabolizeshormones• Secretesimmunecytokines
ClottingandPlasmaProteins
• Produces– Prothrombin– Fibrinogen– Plasmaalbumin• Regulatesbloodvolume
– Acutephaseproteins– Bindingproteins– Lipoproteins
OrganicMetabolism
• Convertsplasmaglucosetoglycogenandtriglycerides
• Convertsaminoacidstofattyacids• Producestriglyceridesandsecretesthemaslipoproteins
• Gluconeogeneisisandglycogenolysis• Convertsfattyacidsintoketones• Producesurea
CholesterolMetabolism/Excretory&DegradativeFunctions
• Synthesizescholesterol• Convertsplasmacholesterolintobilesalts– BilesaltsneededforvitaminKabsorption
• Excretestoxinsviabile• Destroysolderythrocytes• …andlots,lotsmore!