Physiology Review 1

8/6/2019 Physiology Review 1

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PhysiologyTopicsfortheExam:Review/Pictures(BasedonDoc.Motocsslides,GuytonsMedicalPhysiology,Wikiandsomepersonalextras)

N1:Digestionintheoralcavity

Asfoodenterstheoralcavitythecheeksandtheclosedlipsholdfood

betweentheteeth,thetonguemixesthefoodwithsalivatosoftenit,

andtheteethcutandgrinditintoabolus.Thetongueinitiatesthevoluntaryphaseofdeglutition.Thetipofthetongueisplaceonthe

hardpalate,andthencontractswhichforcesthebolusintothe

oropharynx.

*Salivarysolutes?Getalist!(SalivarypH=6,8)

Salivaryamylase(beginsstarchdigestion,worksatneutralpH,

isinactivatedbythestomachspH)

Linguallipase(inactiveatneutralpH,activatedinthestomach) Mucus(lubricationandbindingsoffoodintobolus) Lysozyme(killsbacteria) IgA(inhibitsbacteriasgrowing) Electrolytes

***furtherinfosattopicn10

N2:MotilityoftheStomach

Thebolusismixedwithgastricjuicetoformchime.Thisispossible

becauseofthe3musclelayersofthestomach(longitudinal,circular

andoblique),andthecontractionofthepyloricsphincter.

Thepropulsionphase:

Afterameal,peristalsisbeginsnearthecardiacregionandmoves

towardthepyloricsphincter.Theintensityofthemovementsisdue

totheincreaseinthenumberofmusclelayersofthestomach.The

pyloricregionholdsabout30mlofchyme.Itallowsonlyliquidsand

smallparticlesofchyme,about3ml,topassthroughthevalvefor

eachperistalticwave.Thecontractionsofthepyloriusdecreasethe

openingofthevalve.Thisresultsintheremainingchymebeing

remixedagainandagain.Therateofperistalticwavesisconstant

3/min.,however,theintensitycanbemodified.Thiscontractile

rhythmissetbythespontaneousactivityofpacemakercellslocated


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inthelongitudinalsmoothmusclelayer.Thesecellsestablishthe

basicelectricalrhythmofthestomach.Thestomachusuallyempties

completelywithin4hoursafterameal.Therateofgastricemptying

dependsonthecontentsoftheduodenumasonwhatishappeningin

thestomach.

N3:Gastrointestinalsmoothmuscle

SeveraldifferentlayersformtheGItractstructures(fromthe

internaltotheexternalportion):

Epithelium Laminapropria(containslymphnodes) Muscularismucosae

Submucosa(andhisglands) Circularlayer


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Longitudinallayer Serosa

ElectricFeatures:

Restingpotentialis-40to-80mV(usuallynearthelowerendofthisrange).ElectrogenicNa/K-ATPasemaycontributemoretoresting

potential.Slowwaves(3to12perminute)areoscillationsofresting

membranepotential.Actionpotentialsareslowwithlittleovershoot

(L-typeCa2+channelsinvolved)

InterstitialcellsofCajalgenerateslowwaves.Theiramplitude(and

frequency)isinfluencedbynervesandhormones.Contractionsmay

occurintheabsenceofactionpotentials.Whenactionpotentials

occur,contractionismoreforceful

N4:Neurologicalandhormonalcontrolofthestomach


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*Bythewayslidesmaybealittleconfused,takeitstepbystepwouldbehelpful:

1. CephalicPhase:stageinwhichthestomachrespondstosight,smell,tasteorthoughtoffood,thesesensoryandmentalinputsconvergeonhypothalamusreleasingsignalstothemedulla

oblongata.Fromthispointsignalsaretransmittedtothe

VAGUSNERVEstimulatinggastricactivity

2.Gastricphase:aperiodinwhichswallowedfoodandsemi-digestedproteinsactivategastricactivity,2/3ofgastric

secretionsoccurinthisphase,ingestedfoodstimulatesgastric

activityin2ways,bystretchingthestomachandbyraisingthe

pHofitscontents.Thesestretchesactivate2reflexes,ashort

onebythemyentericnerveplexusandalongonebythevagusandthebrainstem.*NOWREVIEWTHEGASTRICSECRECTIONS

3. Intestinalphase:stageinwhichtheduodenumrespondstothearrivingchime.Firstitenhancesgastricsecretionsbutsoon

inhibitsit.

MECHANICALDIGESTION,PROPULSION:

1.Pace-makercells--interstitialcellsofCajalestablishintrinsic

control.

2.Vagusnervecontrolmechanicaldigestionextrinsically.

MECHANICALDIGESTION:

1. Gastrin--stimulategastricemptying2. Serotonin--contractionofsmoothmuscle3.

Somatostatin--inhibitsmotilityandemptying4. Secretin--inhibitsgastricmotility

5. GastricInhibitoryPeptide--inhibitsgastricmotility

PROPULSION:

1.Gastrin--stimulatesemptying

2.Somatostatin--inhibitsgastricmotilityandemptying

3.Secretin--inhibitsgastricmotilityandemptying

4.GastricInhibitoryPeptideinhibitsgastricmotilityandemptying


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N5Physiologicaleventsinthesmallintestine(Ifyougetthisoneyourluckisfallingdownapart)

Theseeventscanbedividedin:

1. Mechanicaldigestion:MOTILITY

Insegmentation,nonadjacentsegmentsoftheintestinealternately

contractandrelax,movingthechymeforwardandthenbackward

resultingthroughmixing.Thisresultsinthechymebeingwellmixed

withtheenzymesfromtheliverandthepancreas.Inaddition,segmentationensuresthatthechymewellmovetotheplasmamembraneoftheliningcellsofthesmallintestine.Thesesimple

columnarepithelialcellshavebrushborderenzymeswithintheir

plasmamembrane,whichcompletethechemicaldigestionofthe

chyme.Onebyonewecanreadbelowthesekeyfeatures:

Contractions,servestomixchimewithintestinaljuice,bile,pancreaticjuiceandneutralizeacidinordertodigestnutrients

moreeffectively.Ithelpstobringthechimeincontactwiththe

mucosafornutrientabsorptionandtomoveresiduestowardtheintestine.

Segmentationisamovementinring-likeconstrictions,commonofseveralplacesoftheintestine.

Pacemakercellsofmuscolarisexternasettherhythmofsegmentations,contractingit12times/minuteinduodenum

and8-9times/minuteinileum.Segmentationprocessesslow

downasthechimeprogressestowardthecolon.


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2. Chemicaldigestion:(GoodLuck!) Carbohydrate,firstlybysalivaryamylase,thenbypancreatic

amylaseandbrushborderenzymes.(Fromstarchto

oligosaccharides,fromthisonetomaltoseandfinallyto

glucosereadytobeabsorbed)

Proteins,hydrolyzedbypepsin,trypsinandchymotrypsin.(Breakingallpeptidesbondswehavetounderlinetheaction

oftreemoreenzymes:Carboxypeptidase,Aminopeptidse,

Dipeptidase) Lipids,mainlyby:lipases(lingualandpancreatic),important

featuresofemulsificationandreducingdropletsintosmaller

onesmadebybilecomponents.


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Peristalsisbeginsinduodenum,travels10/70cmanddiesouttobefollowedbyanotherwave,beginsalittlefurtherdownthanthefirst

onedid.

N6NeurologicalandHormonalcontrolofthesmallintestine

Intrinsicpacemakercellsinlongitudinalsmoothmusclelayerinitiate

segmentation.Gastrinstimulatescontractionofthesmoothmuscleof

thesmallintestines.Thisresultsinanincreaseinsegmentation.

Perstalsisisstimulatedbygastrin.Also,gastrinrelaxestheileocecal

valve,whichallowchymeintothelargeintestines.

N7RegulationofGISecretions,Generalities(LOL!)

ThereareseveraltypesofstimulationoftheAlimentarytractglands:

Themechanicalpresenceoffoodstimulateglandsofthatregiontosecretjuices

Hormonalandneuralstimulitotheparasympatheticnervesrisemostofthesecretions

Thesympatheticnervesstimulationhastworoles:itcanslightlyincreasethesecretionswhenrunaloneanditcanbe

superimposedtotheparasympatheticoneifitisalready

causingcopioussecretionsbyglands.

Takingafurtherlookforthemotilityandsecretionregulationitis

quitebettertotalkabouttheharmonybetweenENS,CNSandGI

peptides.

CentralnervoussystemtriggerslongreflexestotheGItract,cooperatingwiththeESN,externalstimulibymanysensory

structuresandemotionalstatuses(likebutterflyinthe

stomachfeeling)*mediatedbyVagusandBrainstem

Entericnervoussystemheadtheshortreflexes(thissystemstandalonefromthebrainandregulateitself)*mediatedbythemyentricnerveplexus

Forcompleteness:theGIpeptidesaresignalmoleculesthatarereleasedintothebloodbytheGIcells.Theyactonavarietyof

tissuesincludingthebrain,digestiveaccessoryorgans,andtheGItract.Theeffectsrangefromexcitatoryorinhibitoryeffects


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onmotilityandsecretiontofeelingsofsatietyorhungerwhen

actingonthebrain.

N8TypesofGIhormonesandtheirrole

Epithelialcellsliningthelumenofthestomachandsmall

intestinesecretetheclassicalGIhormones.Thesehormone-

secretingcells(endocrinocytes)areinterspersedamongamuch

largernumberofepithelialcellsthatsecretetheirproducts(acid,

mucus,etc.)intothelumenortakeupnutrientsfromthelumen.GI

hormonesaresecretedintoblood,andhencecirculatesystemically,

wheretheyaffectfunctionofotherpartsofthedigestivetube,liver,

pancreas,brainandavarietyofothertargets.

Thereareabunchofhormones,neuropeptidesand

neurotransmittersthataffectgastrointestinalfunction.Interestingly,

anumberoftheclassicalGIhormonesarealsosynthesizedinthe

brain,andsometimesreferredtoas"brain-gutpeptides".The

significanceofthispatternofexpressionisnotclear.

Onebyonereview:

Gastrinisamajorphysiologicalregulatorofgastricacidsecretion.Italsohasanimportanttrophicorgrowth-

promotinginfluenceonthegastricmucosa.Gastrinis

synthesizedinGcells,whicharelocatedingastricpits,

primarilyintheantrumregionofthestomach.Theprimarystimulusforsecretionofgastrinisthepresenceofcertain

foodstuffs,especiallypeptides,certainaminoacidsand

calcium,inthegastriclumen.ItisinhibitedbyalowpH.Itsmainfeatureistostimulategastricacidsecretionandto

promotemucosalgrowth.

Cholecystokininplaysakeyroleinfacilitatingdigestionwithinthesmallintestine.Itissecretedfrommucosal

epithelialcellsinthefirstsegmentofthesmallintestine

(duodenum),andstimulatesdeliveryintothesmallintestineof

digestiveenzymesfromthepancreasandbilefromthe

gallbladder.Cholecystokininisalsoproducedbyneuronsinthe

entericnervoussystem,andiswidelyandabundantlydistributedinthebrain.Themostpotentstimuliforsecretion


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ofcholecystokininarethepresenceofpartiallydigestedfats

andproteinsinthelumenoftheduodenum.Thishormonehas

theeffectoftriggeringthereleasedigestiveenzymesfrom

thepancreasintotheduodenumandtotriggercontractionof

thegallbladdertodeliverbileintotheduodenum. Afloodofacidfromthestomachperiodicallyassaultsthesmall

intestine,anditisimportanttoputoutthatfireinahurryto

avoidacidburns.ThisroleistakenbySecretin,witha

principaltargetforthepancreas,whichrespondsbysecreting

abicarbonate-richfluid,whichflowsintothefirstpartofthe

intestinethroughthepancreaticduct.Bicarbonateionisabase

andservestoneutralizetheacid,thuspreventingacidburns

andestablishingapHconducivetotheactionofotherdigestive

enzymes.Asacidisneutralizedbybicarbonate,theintestinalpHrisestowardneutrality,andsecretionofsecretinisturnedoff.

Gastricinhibitorypeptide(GIP)isamemberofthesecretinfamilyofhormones.Likesecretin,itissecretedfrommucosalepithelialcellsinthefirstpartofthesmallintestine.Another

activityofGIPisitsabilitytoenhancethereleaseofinsulinin

responsetoinfusionsofglucose.Forthisaction,ithasalso

beenreferredtoasglucose-dependentinsulinotropicpeptide.

Forcompleteness: Ghrelin:appearstobeastrongstimulantforappetiteand

feeding;alsoapotentstimulatorofgrowthhormonesecretion. Motilin:apparentlyinvolvedinstimulatingpatternsofmotility

inthestomachandsmallintestine

Serotonin:increaseintestinalmotility SubstanceP:readabove Vasoactiveintestinalpeptide(VIP):neurotransmitterfor

intestinalsmoothmusclestimulatessecretionofwaterand

ions Neurotensin:decreasesintestinalmotilityincreasesbloodflow

toileum

Histamine:increaseHClsecretion

N9Gastrin(DamnIshouldhavenotwritesomuchbefore)

Dontloosetimewithgeneralities;gastrinisahormonethat

stimulatessecretionofgastricacid(HCl)bytheparietalcellsofthe

stomachandaidsingastricmotility.Gcellsinthestomach,duodenum,andthepancreasreleaseit.Itsreleaseisstimulatedby


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peptidesinthelumenofthestomach.Loosetimeforitsfunctions:

Thepresenceofgastrinstimulatesparietalcellsofthestomachto

secretehydrochloricacid(HCl)/gastricacid.Thisisdoneboth

directlyontheparietalcellandindirectlyviabindingontoCCK2/gastrinreceptorsonECLcellsinthestomach,whichthen

respondsbyreleasinghistamine,whichinturnactsinaparacrine

manneronparietalcellsstimulatingthemtosecreteH+ions.Thisis

themajorstimulusforacidsecretionbyparietalcells.

Alongwiththeabovementionedfunction,gastrinhasbeenshownto

haveadditionalfunctionsaswell:

Stimulatesparietalcellmaturationandfundalgrowth. Causeschiefcellstosecretepepsinogen,thezymogen(inactive)formofthedigestiveenzymepepsin. Increasesantralmusclemobilityandpromotesstomach

contractions.

Strengthensantralcontractionsagainstthepylorus,andrelaxesthepyloricsphincter,whichstimulatesgastric

emptying.

Playsaroleintherelaxationoftheileocecalvalve.[7] Inducespancreaticsecretionsandgallbladderemptying.[8] Impactsloweresophagealsphincter(LES)tone,causingitto

relax.[9]Takingthisintoconsideration,highlevelsofgastrin

mayplayaroleinthedevelopmentofsomeofthemore

commonLESdisorderssuchasacidrefluxdisease.

DieseaseStates:Excessivesecretionofgastrin,orhypergastrinemia,isawell-

recognizedcauseofaseverediseaseknownasZollinger-Ellisonsyndrome,whichisseenatlowfrequencyinmananddogs.Thehallmarkofthisdiseaseis

gastricandduodenalulcerationduetoexcessiveandunregulatedsecretionofgastricacid.Mostcommonly,hypergastrinemiaistheresultofgastrin-secreting

tumors(gastrinomas),whichdevelopinthepancreasorduodenum.

N10CompositionandroleofSaliva(Illbefastonthisone)

Keyfeatures:

Moistensmouth Digestsalittlepartofstarchandfat Cleansesteethandinhibitsbacterialgrowth Dissolvesmoleculessotheycanstimulatetastebuds


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Moistensfoodsandbindsparticlestogethertohelpswallowingprocess

Itisanhypotonicsolutionof91upto99.5%ofwaterand

Thesefollowingsalivarysolutes:

Salivaryamylase,beginsstarchdigestion Linguallipase,activatedbystomachacid(youknow) Mucus,bindsandlubricatesthefoodmass Lysozyme,killsbacteria Ig-A,inhibitsbacterialgrowing Electrolytes:Na+,K+,HCo3-,Cl-,Po4- Organicsubstances:urea,uricacidsresidues

Forcompletenesssalivaisdividedintwomainproteinsecretion:

a. Aserousone,thatcontainsptyalin(an-amilase)b. Amucuskindthatcontainsmucin,lubricatingandsurface

protectivesubstance.

N11SecretionofSaliva

Thedailysecretionisaround1.5L,whilethebasalflowcanbeof0,5

upto5mLperminute.

Itismadeby:

Parotidgland:producewateryfluid(serous) Submandibularglands:bothwaterandmucus Sublingual:mainlymucus

Itisanisotonic(290-310mOsm/L)fluidsimilartotheplasmatic

ultra-filtrate,butwithanhigherconcentrationofK+

Salivaisproducedinandsecretedfromsalivaryglands.Thebasic

secretoryunitsofsalivaryglandsareclustersofcellscalledacini.

Thesecellssecreteafluidthatcontainswater,electrolytes,mucus

andenzymes,allofwhichflowoutoftheacinusintocollectingducts.

Withintheducts,thecompositionofthesecretionisaltered.Muchof

thesodiumisactivelyreabsorbed,potassiumissecreted,andlarge

quantitiesofbicarbonateionaresecreted.Bicarbonatesecretionisof

tremendousimportancetoruminantsbecauseit,alongwithphosphate,providesacriticalbufferthatneutralizesthemassive


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quantitiesofacidproducedintheforestomachs.Smallcollecting

ductswithinsalivaryglandsleadintolargerducts,eventually

formingasinglelargeductthatemptiesintotheoralcavity.

N12Regulationofsalivarysecretion

Secretionofsalivaisundercontroloftheautonomicnervoussystem,

whichcontrolsboththevolumeandtypeofsalivasecreted.Potent

stimuliforincreasedsalivationincludethepresenceoffoodor

irritatingsubstancesinthemouth,andthoughtsoforthesmellof

food.Knowingthatsalivationiscontrolledbythebrainwillalsohelp

explainwhymanypsychicstimulialsoinduceexcessivesalivation-

forexample,whysomedogssalivatealloverthehousewhenit's

thundering.

Autonomicnervoussystemcontrolitsregulation:

Parasympathetic(ACh,VIP):

Highandsustainedoutput Synthesisandsecretionofamylaseandmucins Transportactivityofductularepithelium Vasodilationandincreasedbloodflow Positivefeedbackonbloodsupplythroughkallikrein-

kininogensystem

StimulationofglandularmetabolismandgrowthSympathetic:

Transientincreaseofsecretion Vasoconstrictionleadstodecreaseofsalivation

N13GastricJuice

Thestomachisfamousforitssecretionofacid,butacidisonlyoneof

fourmajorsecretoryproductsofthegastricepithelium,allofwhich

areimportanteithertothedigestiveprocessortocontrolofgastric

function:

Mucus:Themostabundantepithelialcellsaremucouscells,whichcovertheentirelumenalsurfaceandextenddownintothe

glandsas"mucousneckcells".Thesecellssecretea

bicarbonate-richmucusthatcoatsandlubricatesthegastricsurface,andservesanimportantroleinprotectingthe


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epitheliumfromacidandotherchemicalinsults.

Acid:Hydrochloricacidissecretedfromparietalcellsintothelumenwhereitestablishesanextremelyacidicenvironment.

Thisacidisimportantforactivationofpepsinogenand

inactivationofingestedmicroorganismssuchasbacteria.Proteases:Pepsinogen,aninactivezymogen,issecretedinto

gastricjuicefrombothmucouscellsandchiefcells.Once

secreted,pepsinogenisactivatedbystomachacidintothe

activeproteasepepsin,whichislargelyresponsibleforthe

stomach'sabilitytoinitiatedigestionofproteins.Inyoung

animals,chiefcellsalsosecretechymosin(rennin),aprotease

thatcoagulatesmilkproteinallowingittoberetainedmore

thanbrieflyinthestomach.

Hormones:Theprincipalhormonesecretedfromthegastricepitheliumisgastrin,apeptidethatisimportantincontrolofacidsecretionandgastricmotility.

Gastricepithelialcellssecreteanumberofotherenzymes,including

alipaseandgelatinase.Onesecretoryproductofconsiderable

importanceinmanisintrinsicfactor,aglycoproteinsecretedby

parietalcellsthatisnecessaryforintestinalabsorptionofvitaminB12.

N14SecretionoftheStomach(why?Gastricjuicewasntenough???DAMN)

1part:MechanismofAcidSecretion

Thehydrogenionconcentrationinparietalcellsecretionsisroughly

3millionfoldhigherthaninblood,andchlorideissecretedagainst

bothaconcentrationandelectricgradient.Thus,theabilityofthe

partietalcelltosecreteacidisdependentonactivetransport.

ThekeyplayerinacidsecretionisaH+/K+ATPaseor"protonpump"

locatedinthecannalicularmembrane.ThisATPaseismagnesium-

dependent,andnotinhibitablebyouabain.Thecurrentmodelforexplainingacidsecretionisasfollows:

Hydrogenionsaregeneratedwithintheparietalcellfromdissociationofwater.Thehydroxylionsformedinthisprocess

rapidlycombinewithcarbondioxidetoformbicarbonateion,a

reactioncataylzedbycarbonicanhydrase.

Bicarbonateistransportedoutofthebasolateralmembraneinexchangeforchloride.Theoutflowofbicarbonateintoblood

resultsinaslightelevationofbloodpHknownasthe"alkalinetide".ThisprocessservestomaintainintracellularpHinthe


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parietalcell.

Chlorideandpotassiumionsaretransportedintothelumenofthecannaliculusbyconductancechannels,andsuchisnecessary

forsecretionofacid.

Hydrogenionispumpedoutofthecell,intothelumen,inexchangeforpotassiumthroughtheactionoftheprotonpump;potassiumisthuseffectivelyrecycled.

Accumulationofosmotically-activehydrogenioninthecannaliculusgeneratesanosmoticgradientacrossthe

membranethatresultsinoutwarddiffusionofwater-the

resultinggastricjuiceis155mMHCland15mMKClwitha

smallamountofNaCl.

ControllingtheAcid:Parietalcellsbearreceptorsforthreestimulatorsofacidsecretion,reflectingatriumverateofneural,

paracrineandendocrinecontrol:

Acetylcholine(muscarinictypereceptor)GastrinHistamine(H2typereceptor)

2Part:PepsinogenandPepsin

Pepsinsaretheprincipalproteasesingastricsecretionsofadult

mammals.Theyaremembersofthefamilyofasparticproteases,and

closelyrelatedtochymosin,anothergastricproteaseexpressed

particularlyinyounganimals.Theseenzymesaresynthesizedand

secretedpredominantlybychiefcellsinthegastricmucosa.

Pepsinsaresynthesizedasinactivepre-proenzymes,consistingofa

signalpeptide,activationpeptideandactiveenzyme.Thesignal

peptideiscleavedastheproteinisinsertedintoendoplasmicreticulumandtheresultingproenzyme-pepsinogen-istransported

totheGolgiandcondensedintosecretorygranules.

Pepsinogensaresecretedinaformsuchthattheactivationpeptide

assumesacompactstructurethatoccludestheactivesite.On

exposuretoanacidic(pHStructurally,theactivesiteislocatedina

deepcleftwithinthemolecule.OptimalactivityofpepsinsisatpHof

1.8to3.5,dependingontheisoform.Theyarereversiblyinactivated

ataboutpH5andirreversiblyinactivatedatpH7to8.


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Ingeneral,secretionofpepsinogensiscoupledtosecretionofacid

fromtheparietalcell.Invitrostudieshavedemonstratedthatagents

thatstimulateeitheroftwoconditionseffectivelystimulate

secretion:

ElevatedintracellularlevelsofcyclicAMP:examplesincludesecretin,vasoactiveintestinalpeptideandepinephrine.

Elevatedintracellularcalcium:theprincipalmediatorsinvestigatedincludeacetylcholineandpeptidesofthe

gastrin/cholecystokininfamily

3Part:IntrinsicFactor

Intrinsicfactorisaglycoproteinsecretedbyparietal(humans)orchief(rodents)cellsofthegastricmucosa.Inhumans,ithasan

importantroleintheabsorptionofvitaminB12(cobalamin)inthe

intestine,andfailuretoproduceorutilizeintrinsicfactorresultsin

theconditionperniciousanemia.

DietaryvitaminB12isreleasedfromingestedproteinsinthestomach

throughtheactionofpepsinandacid.Itisrapidlyboundbyoneof

twovitaminB12-bindingproteinsthatarepresentingastricjuice;at

acidpH,thesebindingproteinshaveagreateraffinityforthevitamin

thandoesintrinsicfactor.Inthesmallintestine,pancreaticproteases

digestthebindingproteins,releasingvitaminB12,whichthen

becomesboundtointrinsicfactor.Finally,therearereceptorsfor

intrinsicfactorontheilealmucosa,whichbindthecomplex,allowing

vitaminB12tobeabsorbedintoportalblood.

4Part:Chymosin(Renin)

Chymosin,knownalsoasrennin,isaproteolyticenzymesynthesized

bychiefcellsinthestomach.Itsroleindigestionistocurdleor

coagulatemilkinthestomach,aprocessofconsiderableimportance

intheveryyounganimal.Ifmilkwerenotcoagulated,itwould

rapidlyflowthroughthestomachandmisstheopportunityforinitial

digestionofitsproteins.

Chymosinefficientlyconvertsliquidmilktoasemisolidlikecottage

cheese,allowingittoberetainedforlongerperiodsinthestomach.

Chymosinsecretionismaximalduringthefirstfewdaysafterbirth,

anddeclinesthereafter,replacedineffectbysecretionofpepsinas


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themajorgastricprotease.

Chymosinissecretedasaninactiveproenzymecalledprochymosin

that,likepepsin,isactivatedonexposuretoacid.Chymosinisalso

similartopepsininbeingmostactiveinacidicenvironments,whichmakessenseconsideringitsmission.

N15Hydrochloricacidsecretion(forthemechanismreadaboveJ)

Thebest-knowncomponentofgastricjuiceishydrochloricacid,the

secretoryproductoftheparietal,oroxynticcell.Itisknownthatthe

capacityofthestomachtosecreteHClisalmostlinearlyrelatedtoparietalcellnumbers.

Whenstimulated,parietalcellssecreteHClataconcentrationof

roughly160mM(equivalenttoapHof0.8).Theacidissecretedinto

largecannaliculi,deepinvaginationsoftheplasmamembranewhich

arecontinuouswiththelumenofthestomach.

Whenacidsecretionisstimulatedthereisadramaticchangeinthe

morphologyofthemembranesoftheparietalcell.Cytoplasmictubulovesicularmembranes,whichareabundantintherestingcell


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virtually,disappearinconcertwithalargeincreaseinthe

cannalicularmembrane.Itappearsthattheprotonpumpaswellas

potassiumandchlorideconductancechannelsinitiallyresideon

intracellularmembranesandaretransportedtoandfusedintothe

cannalicularmembranejustpriortoacidsecretion.

Theepitheliumofthestomachisintrinsicallyresistanttothe

damagingeffectsofgastricacidandotherinsults.Nonetheless,

excessivesecretionofgastricacidisamajorprobleminhumanand,

toalesserextent,animalpopulations,leadingtogastritis,gastric

ulcersandpepticaciddisease.Asaconsequence,theparietalcelland

themechanismsitusestosecreteacidhavebeenstudiedextensively,

leadingtodevelopmentofseveraldrugsusefulforsuppressingacid

secretion.

N16Protectivemechanismofthestomach(Quiteso!)

Thegastrointestinalmucosaformsabarrierbetweenthebodyanda

luminalenvironment,whichnotonlycontainsnutrients,butisladen

withpotentiallyhostilemicroorganismsandtoxins.Thechallengeis

toallowefficienttransportofnutrientsacrosstheepitheliumwhile

rigorouslyexcludingpassageofharmfulmoleculesandorganisms

intotheanimal.Theexclusionarypropertiesofthegastricand

intestinalmucosaarereferredtoasthe"gastrointestinalbarrier".

Thegastrointestinalbarrierisoftendiscussedashavingtwo

components:

Theintrinsicbarrieriscomposedoftheepithelialcellsliningthedigestivetubeandthetightjunctionsthattiethemtogether.

Theextrinsicbarrierconsistsofsecretionsandotherinfluencesthatarenotphysicallypartoftheepithelium,butwhichaffect

theepithelialcellsandmaintaintheirbarrierfunction.Thegastricmucosalbarrieristhepropertyofthestomachthat

allowsittocontainacid.

Ifthebarrierisbroken,asbyacetylsalicylicacid(ASS,aspirin)inacid

solution,aciddiffusesbackintothemucosawhereitcancause

damagetothestomachitself.

Thebarrierconsistsofthreeprotectivecomponents.Theseprovide

theadditionalresistanceforthemucosalsurfaceofthestomach:

Acompactepithelialcelllining,tightjunctionsthatrepelharshfluidsthatmayinjurethestomachliningbindcellsinthe


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epitheliumofthestomach.

Aspecialmucuscovering:themucuscoveringisderivedfrommucussecretedbysurfaceepithelialcellsandmucosalneck

cells.Thisinsolublemucusformsaprotectivegel-likecoating

overtheentiresurfaceofthegastricmucosa.Themucusprotectsthegastricmucosafromautodigestionbye.g.pepsin

andfromerosionbyacidsandothercausticmaterialsthatare

ingested.

Bicarbonateions,secretedbythesurfaceepithelialcells.Thebicarbonateionsacttoneutralizeharshacids.

N17Regulationofgastricsecretions(arewejoking???)

READSOMEOFTHEABOVEMENTIONEDPOINTS!!!(4,5,7)

N18Cholecystokinin(Name!)==>READN8

N19Secretin==>READN8

N20Imtoosleepyletsreviewitontheseconddocument!!!

Thatsallfortodayfolks,tomorrowIwouldliketostartfrom

hereandfinishwiththerespiratorysystem(oratleastIhope

so)

Hopeitwillbeuseful;ifImissedsomethingorIwrotehogwash

pleasetellmesoIdfixeverything

YourBelovedcolleague,AlessandroMotta

Maytheforcebewithyou

Physiology Review 1

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