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SYSTEMIC EFFECTS OF

SURGICAL STRESS

M.BHARATHIDASAN

MVM 13048

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WHAT IS STRESS?

Inphysicstheamountofpressureapplieduntilthebreakingpointisreached

Inbiology:Stressisanenvironmentaleffecton

anindividualwhichover-taxesitscontrolsystemsandresultsinadverseconsequences,eventuallyreducedfitness.(Broom&Johnson,2000)

Threats=internalandexternal(stressors) Homeostasis,e.g.pHofblood

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STRESS RESPONSE

Body Reacts to external stimuli, ranging from minor tomassiveinsultbothlocally&generally.

General response - form of wide spread endocrinal,metabolic&biochemicalreactionsthroughoutthebody.

Magnitudeofresponseishighlydependentontheseverity,intensity&durationofstimulus.

For triggering such reflex response & presenting acomplexinterplayofsubstances

Betweenhypothalamicpituitaryaxis, theclassicalneuro-endocrinalhormonesystem&

autonomicnervoussystem-broughttoaction-calledstressresponseoralarmreaction.

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local response -great importance forhealinganddefenseagainstinfection.

It involvesmediators,vascularendothelialcellproducts&eventheintracellularproductsofsinglecells.

Stress response leads to secretion of many anabolic &catabolic hormones resulting in hyper metabolism, -accelerationmostbiochemicalreactions

Response play as compensatory mechanism & provides

maximumchancesofsurvival

Byincreasedcardio-vascularfunctions,fluidpreservationandsupply of the increased demands for energy generatingsubstrates.

Stressresponseprolonged,continuoushypermetabolicstate

leads-exhaustionofessentialcomponentsofthebody

e.g. glucose,fat,protein,minerals, causing lossofweight,fatigue, decreased resistance, delayed ambulation andincreasedmorbidityandmortality

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THE NET EFFECT OF STRESS RESPONSE

THE NEURO-ENDOCRINAL OUTFLOW

Cardiovascularchanges:-cardiacoutput,heartrate,blood pressure, increased myocardial contractility,increaseoxygendemand.

Blood volume distribution : Peripheral & splanchnicvasoconstriction,coronary&cerebralvasodilatation.

RespiratoryChanges:-Increasedrespiratoryrate.

Fluid and electrolyte changes :- Sodium & water

retention.

Coagulation:-Hypercoagubility&fibrinolysis.

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Immunosuppression:-WoundInfections.

Metabolic Changes : Substrate mobilization -hyperglycemia.

Urinarychanges:reducedurinaryoutput.

Thestresschanges -well toleratedby normal healthy

patients.

Returntonormalinduecourseoftime.

In patients systemic diseases, these changes are lifethreatening.

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PRIMARY STIMULI OF NEUROENDOCRINE REFLEXES

Hypotension

Reduction - effective circulating volume due to any reason(trauma,haemorrhage,burns,sepsis,neurogeniccollapseetc.)

It is sensed by - pressure sensitive baroreceptors in aorta,

carotid&renalarteries,

Proportionaltothemagnitudeofthevolumeloss,

Directly through central autonomic pathway to activate releaseofpituitaryhormones

Such as ACTH, vasopressin, growth hormone, beta endorphinandindirectlythroughsympatheticnervoussystem

Toactivatethereleaseofcatecholamine,glucagon,

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Inhibitinginsulinrelease&resultinginretentionofsodium

andwater,riseinheartrate,bloodpressureandbloodsugar.

Decrease in renal blood flow due to splanchnicvasoconstriction

It is sensed by the high pressure stretch receptors atjuxtaglomerularcomplexesofkidney

Resultinginreninandangiotensinsecretionwhichresultsinriseofbloodpressureandreductioninurinaryoutput.

Uneven blood flow for longer time may lead to renal

dysfunction

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OXYGEN, CARBON DIOXIDE

AND HYDROGENION

Changes initiate cardio-vascular, pulmonary andneuroendocrineresponses

throughtheactivationoftheperipheralchemoreceptors,aorticandcarotidbodies.

Decrease in arterial blood flow or oxygen tension,chemoreceptoroxygenextraction,venousPO2.

The 9thand 10thcranial nervescarry thesesensationtothehypothalamusresultingintocardiacsympatheticoutflow

Causing rise in heart rate, cardiac contractility andhyperventilation.

Furtherhypovolemiamaypotentiate thehormonalreflexresponsetohypoxia.

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ANXIETY AND EMOTIONS Fear,anxiety,emotions,tensionsignificantlyreducespaintolerance.

Stimulipasstothelimbicsystemespeciallyintheregionofamygdalahippocampusandlowerbrainstemnuclei

Then transmitting the signals to the posterior

hypothalamus.

Stimulation of which controls the release of varioushormonesfrompituitary.

Pituitary secretesAVP, ACTH, cortisol, aldosteroneand

catecholaminethroughthestimulationoftheANS Itriseinheartrate,bloodpressure.

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TEMPERATURE The change - core temperature is sensed by the pre-opticareaofhypothalamus

Inducesthesecretionofthestresshormones.

The stress hormones increases the heat production but

temperaturealterationsincertainclinicalsituationscanbeseen.

The conditions like hypovolemia with inadequate hepaticbloodflow,starvation,

sepsiswithperipheralvasomotorcontrolburnwithlossofthermal insulationand inducedhypothermiaduringcardio-pulmonary bypass or neurosurgery, profound hypothermiafor total circulatory arrest are known to induce neuro-endocrinalresponses.

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ANAESTHESIA

a.Anesthetic drugs

The use of cyclopropane, ether causes release ofcatecholamine

b.Laryngoscopy and intubationglasso-pharangeal nerve and from tracheo-bronchial tree viathe vagus nerve which enhances the activities of thecervicalsympatheticafferentfibersresultingintransientriseinheartrateandbloodpressure.

c.Light anaesthesia

Duringlightplanesofanaesthesiafeelingofpain,inadequatesleep,amnesiaormusclerelaxationresultsinstressresponse

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The exaggerated pain sensation affects the ascendingreticular,limbicsystem,thalamusandhypothalamus

whichregulatestheautonomic,neuroendocrineresponsebystimulating the hypothalamic-pituitary-adrenalsympathetic axisresulting in releaseofallcatabolicandanabolichormones,beforereachingthecortex.

Thepain sensation causingsympathetic stimulationeven indeeperplanesofanaesthesiaduringskinincision (e.g. rise

inheartrateandbloodpressureduringsternotomy). Surgery :- Thestress response dependson theextentofinjury.

The procedures of short duration,minimum tissue handlingevokeonlyaslightresponse.

The major procedures elicit more pronounced response -which the flow phase may last up to several days orweeks.

This results in excessive weight loss, also delays therecovery,andambulationresultinginincreasedmorbidityand

mortality

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STRESS HORMONES reflexneuroendocrine response tothe injury isconsideredasautocrines,endocrinesandparacrines.

Autocrines (Autonomic response) Catecholamines, insulinandglucagon

Theplasmacatecholaminesincreaseimmediatelyafterinjury&achievepeakconcentrationin24to48hoursdepending

ontheseverity. This exerts metabolic, hemodynamic and hormonemodulatingactions.

Epinephrine causes hepatic glycogenolysis, gluconeogenesis,lypolysis in the adipose tissues, ketogenesis increased

insulinresistance,preventingglucoseuptakebycells.

The direct cardio-respiratory effect increases heart rate,myocardialcontractility,bloodpressureandrespiratoryrate.

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INSULIN Theplasmaconcentrationofinsulinduringstresshasbeennotedtobebiphasic,

characterizedby thesuppression of insulinsecretionfollowedbyanormalsecretion,

whichhasbeentermedasthephaseofphysiologicinsulinresistance.

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ENDOCRINES Hormonesunderhypothalamicpituitarycontrollikecortisol,

thyroxine,AVP,growthHormone. Cortisol

ThecentralkeyistheexcitationofthehypothalamusduringstressresultinginthesecretionofACTH

whichinturninitiatessuddenincreaseincortisollevel

Themetaboliceffectsof cortisol aredirected to overcomethestressfulstate.

Thereisadirect feedbackmechanismforcortisol tobothhypothalamus and pituitary gland to decreasethe

concentrationofcortisolinplasma the potent stress stimuli always initiates either periodicexacerbations of cortisol secretion at multiple times duringthedayorprolongedcortisolsecretionduringchronicstress.

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Cortisolhaswidespreadeffectsonthemetabolism&utilizationofglucose,aminoacidandfattyacidsinhepaticandextra-hepatictissues.

Thecortisolcausesrapidmobilizationofaminoacids

and fat from their cellular stores, making themimmediately available both for energy and synthesisof other compounds including glucose needed bydifferenttissues

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EFFECT OF CORTISOL ON

GLUCOSE METABOLISM

The cortisol and other glucocorticoids have the ability to stimulategluconeogenesisbyliverasmuchas6to10foldsduringstress.

Oneofitseffectisincreaseinglycogenstorageinthelivercellswhichistheprimarysourceofglucoseproduction.

The glucose production during flow phase is mediated through

glucagon and insulin using amino acids, lactates, pyruvates andglyceroletc.

Cortisol mobilizes amino acids from the extra-hepatic tissues andconvertsitintoglucose.

Italsodecreasesanddelaystherateofglucoseutilizationinspiteof increased insulinsecretion,bloodglucoseconcentration increasesupto50%ofthenormal.

Excess of glucoseprovides a ready sourceof energy to obligatetissuessuchasCNS,woundandredcells, since thesecellsdonotrequireinsulinforglucosetransportandutilization.

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PROTEIN METABOLISM Cortisolmobilizesaminoacidsfromtheextrahepaticcells&diminishingthetissuestores.

Increase in catabolism and decreased proteinsynthesis

ResultsInthinningandweaknessofmuscles.

Incontrast,liverincreasestheformationofessentialplasmaproteinsandglucose.

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FAT METABOLISM Cortisolhelpsinmobilizationoffattyacidsfromtheadiposetissues

Italsoincreasesoxidationoffattyacidsinthecells,

changingthemetabolicsystemofthecellsintimes

ofstarvationorstressfromutilizationofglucoseforenergy.

Ketogenesisdependsontheseverityofinjurybutissuppressedbythehighinsulinlevel.

DuringinjurytheperipheralconversionofT4 toT3

isimpaired.

Theplasma concentrationof free and totalT3 aredecreasedafterinjury

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GROWTH HORMONE The secretion of growth hormone is governed byhypothalamicfactors,

autonomicstimulationandnon-hormonalsignals.

TheprimarymetabolicactionofGHduringstressistopromoteproteinsynthesisandenhancelipidbreakdown,andglucosestores.

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ARGININE VASOPRESSIN

Secretion of AVH is increased after major trauma,hemorrhage,sepsis,pain.

ImmediateAVHrelease, following acute reduction ofcirculatingvolume,

It is a complex event acting through afferentsincluding baro, chemoreceptors and left atrialreceptors.

The preservation of water and sodium reduction in

the urine volume occurs as a compensatoryphenomenon.

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ALDESTERONE ACTH and angiotensin increases and stimulates

aldesteroneconcentrationfollowinginjury.

The primary aldesterone secretion is related tosodium and water resorption from the distal

convolutedtubules

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RENIN ANGIOTENSIN Renin release is under the control of juxtaglomerular

neurogenic receptors and the macula densa.

Decreased circulating volume, ACTH, AVP, glucagon,

prostaglandins, potassium, magnesium and calcium influence

the renin secretion.

Angiotensin II acts directly on cardiovascular system, fluid

electrolyte balance, hormonal modulation and metabolism.

It is a potent vaso-constrictor, also stimulates heart rate,

myocardial contractility and increases vascular permeability.

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PARACRINES Theactivatedlocaltissue,vascularendothelialcellsystemandsinglecellinitiatesresponseduringhemorragesepsis

inflammationandotherformofinjury.

It releases the cell derived mediator likes cytokine,leukotrines, prostaglandins, histamine, serotonin, TNF,interleukin I, II, VI, plasminogen activator, ecisanoids,kallikreins-kininsandothermediators.

ThesemediatorsarealsoreleasedasaconsequenceofcellinjuryordeathwhichhavedirecteffectontheANSand CNS on the classical hormone system releasingcortisol,EPandNEandotherstresshormonesinsmallquantity.

Some mediators affect the vascular, metabolic,coagulation,angiotensinandimmunologicalsystem.

The preventive measures for the release of suchmediators may play an important role in reducing thestresshormones

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IMMUNE RESPONSE Infectious complications continue to be one of the causes of

post-operative morbidity.

The body protects itself against foreign organisms or

substances.

The mechanism of Immunosuppression in the post-operative

period is not fully understood.

The known mediators of immune depression are neuro-

endocrine response

Intravenous opioids and inhalational agents which have shownan increase -susceptibility infection through a significant

decrease in - cytotoxic activity of the natural killer cells.