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!