physiology review 1
TRANSCRIPT
-
8/6/2019 Physiology Review 1
1/20
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
-
8/6/2019 Physiology Review 1
2/20
inthelongitudinalsmoothmusclelayer.Thesecellsestablishthe
basicelectricalrhythmofthestomach.Thestomachusuallyempties
completelywithin4hoursafterameal.Therateofgastricemptying
dependsonthecontentsoftheduodenumasonwhatishappeningin
thestomach.
N3:Gastrointestinalsmoothmuscle
SeveraldifferentlayersformtheGItractstructures(fromthe
internaltotheexternalportion):
Epithelium Laminapropria(containslymphnodes) Muscularismucosae
Submucosa(andhisglands) Circularlayer
-
8/6/2019 Physiology Review 1
3/20
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
-
8/6/2019 Physiology Review 1
4/20
*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
-
8/6/2019 Physiology Review 1
5/20
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.
-
8/6/2019 Physiology Review 1
6/20
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.
-
8/6/2019 Physiology Review 1
7/20
-
8/6/2019 Physiology Review 1
8/20
-
8/6/2019 Physiology Review 1
9/20
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
-
8/6/2019 Physiology Review 1
10/20
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
-
8/6/2019 Physiology Review 1
11/20
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
-
8/6/2019 Physiology Review 1
12/20
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
-
8/6/2019 Physiology Review 1
13/20
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
-
8/6/2019 Physiology Review 1
14/20
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
-
8/6/2019 Physiology Review 1
15/20
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
-
8/6/2019 Physiology Review 1
16/20
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.
-
8/6/2019 Physiology Review 1
17/20
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
-
8/6/2019 Physiology Review 1
18/20
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
-
8/6/2019 Physiology Review 1
19/20
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
-
8/6/2019 Physiology Review 1
20/20
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