ContentsPhysiology

I.SalivatorySecretions................................2 II.GastricSecretions....................................2 III.GastricMucosalDisorders.......................2 IV.PancreaticSecretions...............................2 V.BileSecretion...........................................3 VI.IntestinalSecretion..................................3

Nutrition VII.NutritonalEquations................................3VIII.DietaryMacromoleculesandVitamins....3 IX.DietaryMinerals.......................................4

LipidBiochemistry X.LipidSynthesis..........................................4 XI.LipidMetabolism......................................4 XII.Lipoproteins.............................................4XIII.FattyAcidsandObesity............................5

Pharmacology/LaboratoryXIV.Pharmacology...........................................5 XV.LaboratoryTests.......................................5

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TableI SalivatorySecretionsGland Secretion Innervation (salivatorynucleus)Parotid Serous,highamylase Oticganglion(CNIX)Submandibular 4:1seroustomucus,weakamylase,highlysozyme Submandibularganglion(CNVII)Sublingual 4:1mucustoserous Submandibularganglion(CNVII)Oral/buccalmucosa MucusDuct Action EffectIntercalatedducts Secreteprotein

StriatedductsInfluencedbyaldosterone;absorbNa/Cl,secreteK/HCOKH,HCOClexchange

Salivabecomeshypotonictoplasma,alkalineathighsecretions

Excretoryducts Secretedepidermalgrowthfactor,enzymes;lowwaterpermeability Partialdigestionoffood,maintainshypotonicityofsecretionFunctions FactorsinvolvedDigestion amylase,lipase,DNA/RNAseProtection Thiocyanate,sialoperoxidase,IgA/G/M,lysozyme,kallikreinExcretion Glucose,urea,Hg,PbRegulation Effect PathwayParasymathetic Sustainedincreaseinrateupto20x;Na/Cl,K/HCO,protein ACh/SubstanceP/VIP:secretionviaIP

SympatheticSlighttransientincreaseinrate,K/HCO,proteinOveralldecreaseinsecretionduetovasoconstriction

adrenergic:secretionviaIPadrenergic:amylaseviacAMP

Basalrate:11.5L/day,30mL/hr;maximalsecretions:400600mL/hr

TableII GastricSecretionsCell Location Secretions Description

Mucusneck Neckofgastricglands MucusProtectsautodigestionbypepsinwithtightjunctions,mucusgelbarrierpreventsabsorptionStimuatedbyPGE,ACh,HCl,glucagon,VIP;InhibitiedbyNSAIDs,alcohol,bilesalts,agonists

Gcell Pyloricantrum GastrinStimulatesHClsecretion,increasesmotility,mildlyincreasespancreaticenzymereleaseStimulatedbyACh,GRP/bombesin,pH,protein,alcohol,Ca,coffee(AAs);releasedingastricphase

EnterochromaffinDcells Pyloricantrum SomatostatinInhibits ofgastrin,releasedatpH23,inhibitssecretioninsmallint.,pancreas,gallbladderReleasedinintestinalphase

Parietalcell FundusHCl

FormedviaactiveH transport(protonpump);pH0.8,1500cal/LtosynthesizeAlkalinetide:HCOintobloodaftercarbonicanyhdraserxn(CO+HOH+HCO)SecretedwithNa,K,HO;hencevomitingcausesmetabolicalkalosis,increasedratelowers[Na]Highlevelsofacidityarerelatedtoduodenalulcers,gastriculcersaremoreduetomucosaldamage

Intrinsicfactor NecessaryforabsorptionofVitB interminalileumGastroferrin Necessaryforabsorptionofiron induodenum;convertsferric(Fe)toferrous(Fe)

Chiefcell Fundus Pepsinogen StimulatedbyNE/epi,ACh,VIP,CCK,gastrin,H; cleavedtopepsin,onlyproteaseformeatcollagenMastcells Throughout Histamine ActivatesstimulatoryH2receptorsonparietalcells,stimulatedbyfood,ACh,gastin,HCl,pepsinEntericneurons PostganglionicCNX GRP(Bombesin) Stimulatedbyprotein,neuralreflexesincephalicphase;gastrinandpancreaticsecretions

TableIII GastricMucosalDisordersDisorder Description Cause Treatment

AcutesuperficialgastritisBenign,selflimiting;vaguediscomfort,diarrheaSmallerosionsandhemorrhages,normalgastricglands

Commonresponsetoirritants:caffeine,ETOH,antibiotics,NSAIDs,spices,infection

Removeoffendingagent

ChronicatrophicgastritisProgressiveatrophyofglandularepitheliumLossofparietalandchiefcells;littleornoglandactivityResultsinperniciousanemia,HClsecretion

Unknown;H.pylori,ZollingerEllisontumor,cancer,smoking,ETOH,stress,autoimmune

Hblockers,antacids,sucralfate,prostaglandins,VitB

Pepticulcerdisease

Penetrationofmusc.mucosa,mostlyduodenum,antrumPresentswithepigastricpain13haftermeals,relievedbyfood/antacids;N/V,weightloss,bleeding

Excessivepepsin/HCl,ETOH,tobacco,caffeine,H.pylori,NSAIDsHdiffusioncausestissueinjuryreleasinghistamine,whichfurtherstimulatesHCl

Surgical:gastroenterostomy,subtotalgastrectomy,truncalvaogotomy,selectivegastricvagotomyPharm:Hagonists,PPIs,antacids,antimuscarinics,sucralfate,prostaglandinagonists,colloidalBi

Helicobacterpyloriinfection

7595%ofallulcersnotcausedbydrugsorchemicals

Urease:ureaammonia+COProtease:digestsglycoproteinsinmucosaPhospholipases:digestepithelialcellsProteins:immuneresponse,pepsinsecretion

Abxamoxicillin,clarithromycinProtonpumpinhibitorTreatmentforconditionscausedbyinfection

TableIV PancreaticSecretionsComponent Function ImageAcinarcells SpontaneoussecretionsofNa,K,Cl,HCO;stimulatedbycAMP(secretin)orIP/Ca(ACh,VIP,CCK)Extralobularducts SecretinstimulatedsecretionofNa,K,Cl,HCO,especiallyHCO(carbonicanhydrase)Maincollectingduct Cl(in)/HCO(out)exchange,limitedbyhighflowrate(HCO,pHinduct)

Enzyme Secretedby Stimulus Function

Cholecystokinin(CCK) Icells(duod,jej) Fats,AAs,secretinpancreatic secretion,gallbladdercontractiongastricemptying

Secretin Scells(duod,jej) Acid,high/lowosmolaritychyme pancreaticHCO,HOsecretion,cAMP

PancreatitisCauses:alcoholism(90%),gallstones,tumors,hyperlipidemia,postoperative,traumaPresentation:epigastric/LUQpain,leastbothersomewhenbentforward,N/V/D,BP,WBC,Hct,amylase,lipaseTreatment:painrelief,nutritionalsupport,alcoholabstention,oralpancreaticenzymeextract

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TableV BileSecretion Action Description Image

LiverBiledependent Secretedbyhepatocytes,nodirecthumoral/neuronalcontrol;formsprimary(1)acidBileindependent Secretedbybileductepithelium,stimulatedbysecretin;HCO,water

Gallbladder

Storage Holds60mLofbileConcentration ActiveabsorptionofNa(withCl,HO)concentratesbile1220xRelease StimulatedbyCCK(relaxessphincterofOddiatMDP),secretin,vagalstimulation

Gallstones80%arecholesterol,20%arepigment;obstructioncausesfatmalabsorption,hepaticdamage,drugtoxicity,inflammation

SmallIntestineBacterialconversion Formssecondary(2)bileacidsfrom1bileacidsConjugation 2bileacidsareionized,reabsorbedbyepitheliumboundtoproteins

Functions Emulsification,micelletransport,bufferingofgastricacid,excretionofbilirubin,cholesterol,toxins

CycleSynthesis:0.20.6g/day,bilepool:3g,secretorycycles:412/d,sototalsecretion=poolcycles=1236g/dayHenceexcretionroughlyequalssynthesis:urinary30=overweight,>40=obese

TotalEnergyExpenditure

restingmetabolicexpexpenditure+thermiceffectoffood +activeenergyexpenditure

RMR=24Kcal

daykg=.0167

Kcal

min kg;normal0.81Kcal/min(women),1.11.3Kcal/min(men)

TEFisdifficulttoestimate,sogeneralactivity(35%ofRME)isusedAEE:givenforspecificexerciseintermsofKcal/hr;So,estimatedTEE=1.35(RME)+AEE

TableVIII DietaryMacromolecules&VitaminsMolecule

Amountneeded(%ofcaloricintake)

Requiredfunctions Metabolism

Carbohydrate 4565%oftotal Almostexclusivesourceforneurons,RBCs Sucrose=GlcFru,Maltose=GlcGlc,Lactose=GlcGal;occursatbrushborder

Lipids

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TableIX DietaryMineralsMineral Sources Functions Metabolism Deficiency

CalciumDairy,greenleafies,legumes,nuts,grains

Musclecontraction,nervetransmission,clotting,bones,teeth,heartrhythm,cellpermeability

Increasedabsorptionwithvit.D,CHO,protein,acidicenvironment,bodilyneed

Tetany,rickets,osteomalacia,osteoporosis,boneresorption

Sodium Salt,meats,cheeseOsmoticbalance,acid/basebalance(w/PO),cellpermeability,neuronal/musclefxn,GIabsorption

Excretedviakidneys,sensitivetoaldosterone

DehydrationToxicity:HTN

IronMeat,liver,shellfish,yolk,fruit,nuts,legumes,molasses

Heme(70%),myoglobin(5%),storedasferritin(20%),cellularenzymecofactor(5%)

Hemeisslower,mustbereducedfromferric(Fe)toferrous(Fe)byvit.CinSI

WomenneedtwiceasmuchHypochromic,microcyticanemia

Iodine Seafood,iodizedtablesalt Thyroidhormonesynthesis(thyroxine)7080%storedinthyroid;TSHfromant.pituitarystimulatesIuptake

Cretinism,braindamageGoiter:creationofthyroglobulininsteadofthyroxine,hypertrophy

TableX LipidSynthesisAgent Actions Regulators Image

AcetylCoAcarboxylase FormsmalonylCoAusingATPandbiotinascofactorbycitrate,insulin,dephosphorylationbylongchainacylCoA,glucagon,cAMP

FattyAcidSynthesisFromGlucose/Pyruvate

CholesterolSynthesisfromAcetylCoA

MalonylCoA BindstoPsiteofFAsynthaseatstartofeachcycle carnitinepalmitoyltrxansferase1(CPT1)

Malicenzyme Oxidizesmalatetopyruvate,reducesNADPtoNADPH bypyruvate,NADPH;byNADP

PhospholipaseA2Cleavesesterbondat2carbonofglycerolProstaglandinsynthesis,presentinsnakevenom

byphosphorylationbysteroidantiinflammatories

Prostacyclins(PGIs)InhibitsplateletaggregationCausesvasodilation

byeicosapentenoicacid(20:53),PGIsynthasebycyclooxygenase(COX)inhibitors(NSAIDs)

ThromboxaneAStimulatesplateletaggregationCausesvasoconstriction

byarachidonicacid(20:46),TXAsynthasebycyclooxygenase(COX)inhibitors(NSAIDs)

HexosaminidaseACleavesNAcGalfromsialylceramideDeficientinTaySachsdisease;GM2ganglioside

Glucosidase Cleavesglucoseceramide,deficientinGauchers

Cholicacid Basicprecursorofallbileacidsincludingcholesterol

HMGCoAsynthase FormsHMGCoAfromacetylandacetoacetylCoA bycholesterol

HMGCoAreductase Formsmevalonatefrom3hydroxy3methylglutaratebystatins,cholesterol(keylimitingstep)InhibitingHMGCoAreductaseupregulatesLDLrec.

AcylCoAAcyltransferase Formscholesteryloleateesterinsidecell bycholesterolviaLDLbinding

TableXI LipidMetabolismAgent Location Actions Image

Pancreaticlipase SecretedbypancreasTriacylglycerol2monoacylglycerol(2MAG)+2fattyacidsRequiredforpassagethroughintestinalepithelium

FattyacylCoAsynthase Intestinalmucosalcell UsesCoAandATPAMP+PPitoformfattyacylCoAtoregenerateTAGShortchainfattyacids Various 28carbons;unesterified,absorbedbyportalcirculationtoliverMediumchainFAs Various 1012carbons;someesterified,absorbedbyportalandlymphatics

LongchainFAs Various 12+carbons;esterified,absorbedbylymphaticsaschylomicrons

Bilesalts IntestinallumenEmulsification;amphipathicsaltsurroundsTAGforabsorptionCeasesformingbileacidmonomerandstartsformingmicellesatCMC

LipoproteinlipaseOutersurfaceofmostlyadipose,somemuscle

HydrolyzeslipidsinchylomicronsinordertoabsorbTAGsforstorage(adipose)orenergymetabolism(muscle)

Propionicacid Liver Onlyrecoverableenergyproductofcholesterolmetabolism

TableXII LipoproteinsComposition Lipoprotein Transport Destination Components

Chylomicron Dietarytriglyceridesfromintestine Tissues,liverApoB48:neededforformationApoCII:activateslipoproteinlipaseRemnantsreturnedtoliverandareatherogenic

VLDL Endogenous(hepatic)TGsfromliver Tissues ApoB100:receptormediatedcatabolism

LDL(atherogenic) Cholesterol Tissues,liver ApoB100:receptormediatedcatabolismOxidizedLDLstimulatesmacrophages,coagulability

HDL(antiathero) Cholesterol Liver Lowersperipheraltissuecholesterolandreturnsittoliversinceitcannotbemetabolizedintissue

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TableXIII FattyAcidsandObesitySubstance Action RegulationInsulin Promotesfattyacidsynthesisandstorage by cAMP,glucose;releasebyfreeFAs

Hormonesensitivelipase BreaksdownTAGinto3FAs,glycerolinadipocytesDeactivatedbylipasephosphataseActiveinphosphorylatedform

Leptin Promotessatiety,glucoseuptakebymuscles

FreefattyacidsOxidizedinmuscle/livercausingglucoseutilizationandgluconeogenesis,causinghyperglycemiaImpairsinsulinreleasebyinterferingwithcells

byinsulin;FFAscauseshyperinsulinemia,Chronicelevationcausesmuscleinsulinresistance,resultinginglucoseoutputandglucosetolerance,insulinsecretioncausingdiabetes

Metabolicsyndrome:obesity,TGs,HDLc(atherogenicdyslipidemia),HTN,insulinresistance,prothromboticandproinflammatorymarkers(CRP,fibrinogen,coagfactors)

TableXIV GIPharmacology Drug Action Effect ConditionsIndicatedNSAIDs(Aspirin,ibuprofen)

InhibitscyclooxygenasebyacetylationPGIsynthesis,decreasingmucussecretioncausingGIupset

NoneGIrelated

Protonpumpinhibitors(prazole)

BlocksH/Kpumpinparietalcellbycovalentlymodifyingsulfhydrylgroup

IrreversiblyinactivatesHClsecretion,pHDuodenalandgastriculcers,GERD,H.pylori

Hreceptorantagonists(tidine)

CompetetivelyinhibitshistaminemediatedstimulationofH/Kpumpinparietalcell

volume/concentrationofHClsecretion,pHCimetidineinhibitsP450,slowingdrugmetabolism

Duodenalandgastriculcers,GERD,hypersecretorystates

Aluminumhydroxide OHionsreactwithHinsolution Decreasedacidity(pH) ConstipationMagnesiumhydroxide OHionsreactwithHinsolution Decreasedacidity(pH) DiarrheaBismuthsalicylate(PeptoBismol)

Enhancesmucus/HCOsecretionInhibitspepsinactivity,chelatesulcerbase

Enhancedprotectionofepithelium,especiallyatulcers

Ulcers,H.pylori

Sucralfate Formsstickygelwhichadherestoepithelium Enhancedprotectionofepithelium Misoprostol AnalogofPGE;stimulatesmucus/HCOsecretion Enhancedprotectionofepithelium Bulkforminglaxatives(methylcellulose,psyllium)

InsolubletohumandigestiveenzymesAccumulatesbulkinchimeofintestineoverseveraldays

Constipation

Osmoticlaxatives(polyethyleneglycol/lytes)

Altersosmolarityofchime Rapidliquiddiarrhea Endoscopy,colorectalsurgery

Opioids(loperamide[Imodium],diphenoxin)

ActatreceptorsinGItract,poorCNSpenetration DecreaseGImotility Diarrhea

5HTreceptorantagonists(setron)

Blocksserotoninatsitesinvomitingreflex,includingchemoreceptortriggerzone(CTZ)

Veryeffectiveinhibitionofemesis Vomiting

D2receptorantagonists(metaclopramide)

BlocksdopamineatsitesinvomitingreflexAlsoforpromotility:5HTantagonist,5HTagonist

Increasesmotility,depressesvomitingreflex Vomiting,gastroparesis,GERD

TableXV GILaboratoryTestsTest Associatedconditions Condition Elevated DecreasedALT(SGPT) inhepatitis,drugtoxicity;specificforliverdisease Hepatocellularliverdisease ALT,AST;bili,GGT,AP albuminAST(SGOT) inalcoholism(withlowerALT),lessspecificforliver Obstructiveliverdisease Bili,AP,GGT;ALT,ASTAlkalinephosphatase inbileduct,intestine,kidney,placenta,andboneDx Pancreatitis Amy,lip,AST,Na,K,WBC Ca,GGT inbileductdisease Celiacdisease AntigliadinIg DxyloseabsBilirubin direct:impairedliverdisease,indirect:hemolysis Inflammatorybowel(Crohns) ANCAsw/perinuclear H&H,K,Mg,Ca,alb,B,folAlbumin inpoorliverfunction,cirrhosis,malnutrition,kidney Cholecystitis WBC,AP,ALT,AST,bili,amyProthrombintime(PT) inbleedingdisorders,liverdysfunction(clottingfax) Myocardialinfarction CK,CKMB,TropIAmylase inpancreatitis,salivaryhyperamylasemiaLipase inpancreatitis;lip/amyratioinalcoholismTrypsin inpancreatitis,renalfailure;radioimmunoassayBUN inkidneydisease,dehydration,pancreatitisDxyloseabsorption inceliacdisease,malabsorptionANCAs(vsneutrophil) Inflammatoryboweldisease:perinuclearstainingCK(CPK) inmuscledamage,includingcardiacCKMB inMI,specificforMITroponinI inMI,specificforMI