SYSTEMIC EFFECTS OF

SURGICAL STRESS
M.BHARATHIDASAN
MVM 13048
WHAT IS STRESS?
Inphysicstheamountofpressureapplied
untilthebreakingpointisreached
Inbiology:Stressisanenvironmentaleffecton
anindividualwhichover-taxesitscontrol
systemsandresultsinadverseconsequences,
eventuallyreducedfitness.(Broom&Johnson,
2000)
Threats=internalandexternal(stressors)
Homeostasis,e.g.pHofblood

surgery-combinationofmultiplefactorsincluding
anesthesia,medication,tissuetrauma,bloodloss,
andtemperaturechanges--metabolicchanges.
Theyproducethepostoperativestressresponse.
Understandingtheseriesofphysiologicalchanges
(stress response) due to anaesthesia and
surgery.

Thesechangeincardio-vascular,metabolic,fluid
andelectrolytesetc.
Directly affects the condition of patients and
increasestherisk.

STRESS RESPONSE
Body Reacts to external stimuli, ranging from minor to
massiveinsultbothlocally&generally.
General response - form of wide spread endocrinal,
metabolic&biochemicalreactionsthroughoutthebody.
Magnitudeofresponseishighlydependentontheseverity,
intensity&durationofstimulus.
For triggering such reflex response & presenting a
complexinterplayofsubstances
Betweenhypothalamicpituitaryaxis,
theclassicalneuro-endocrinalhormonesystem&
autonomicnervoussystem-broughttoaction-called
stressresponseoralarmreaction.
localresponse-greatimportanceforhealinganddefense
againstinfection.
Itinvolvesmediators,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,fluidpreservationand
supply of the increased demands for energy generating
substrates.
Stressresponseprolonged,continuoushypermetabolicstate

leads-exhaustionofessentialcomponentsofthebody
e.g.glucose,fat,protein,minerals,causinglossofweight,
fatigue, decreased resistance, delayed ambulation and
increasedmorbidityandmortality
THE NET EFFECT OF STRESS RESPONSE
THE NEURO-ENDOCRINAL OUTFLOW

Cardiovascularchanges:-cardiacoutput,heartrate,
blood pressure, increased myocardial contractility,
increaseoxygendemand.
Blood volume distribution : Peripheral & splanchnic
vasoconstriction,coronary&cerebralvasodilatation.
RespiratoryChanges:-Increasedrespiratoryrate.
Fluid and electrolyte changes :- Sodium & water
retention.
Coagulation:-Hypercoagubility&fibrinolysis.
Immunosuppression:-WoundInfections.
Metabolic Changes : Substrate mobilization -
hyperglycemia.
Urinarychanges:reducedurinaryoutput.
Thestresschanges-welltoleratedbynormalhealthy
patients.
Returntonormalinduecourseoftime.
In patients systemic diseases, these changes are life
threatening.
PRIMARY STIMULI OF NEURO-
ENDOCRINE 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,
Directlythroughcentralautonomic pathwaytoactivaterelease
ofpituitaryhormones
Such as ACTH, vasopressin, growth hormone, beta endorphin
andindirectlythroughsympatheticnervoussystem
Toactivatethereleaseofcatecholamine,glucagon,

Inhibitinginsulinrelease&resultinginretentionofsodium
andwater,riseinheartrate,bloodpressureandblood
sugar.
Decrease in renal blood flow due to splanchnic
vasoconstriction
It is sensed by the high pressure stretch receptors at
juxtaglomerularcomplexesofkidney
Resultinginreninandangiotensinsecretionwhichresults
inriseofbloodpressureandreductioninurinaryoutput.
Uneven blood flow for longer time may lead to renal
dysfunction
OXYGEN, CARBON DIOXIDE
AND HYDROGENION
Changes initiate cardio-vascular, pulmonary and
neuroendocrineresponses
throughtheactivationoftheperipheralchemoreceptors,
aorticandcarotidbodies.
Decrease in arterial blood flow or oxygen tension,
chemoreceptoroxygenextraction,venousPO
2
.
The9
th
and10
th
cranialnervescarrythesesensation
tothehypothalamusresultingintocardiacsympathetic
outflow
Causing rise in heart rate, cardiac contractility and
hyperventilation.
Furtherhypovolemiamaypotentiatethehormonalreflex
responsetohypoxia.

ANXIETY AND EMOTIONS

Fear,anxiety,emotions,tensionsignificantlyreducespain
tolerance.
Stimulipasstothelimbicsystemespeciallyintheregion
ofamygdalahippocampusandlowerbrainstemnuclei
Then transmitting the signals to the posterior
hypothalamus.
Stimulation of which controls the release of various
hormonesfrompituitary.

PituitarysecretesAVP,ACTH,cortisol,aldosteroneand
catecholaminethroughthestimulationoftheANS
Itriseinheartrate,bloodpressure.

TEMPERATURE
Thechange - core temperature is sensed by the pre-
opticareaofhypothalamus
Inducesthesecretionofthestresshormones.
The stress hormones increases the heat production but
temperaturealterationsincertainclinicalsituationscanbe
seen.
The conditions like hypovolemia with inadequate hepatic
bloodflow,starvation,
sepsiswithperipheralvasomotorcontrolburnwithlossof
thermalinsulationandinducedhypothermiaduringcardio-
pulmonary bypass or neurosurgery, profound hypothermia
for total circulatory arrest are known to induce neuro-
endocrinalresponses.
ANAESTHESIA
a.Anesthetic drugs
The use of cyclopropane, ether causes release of
catecholamine
b.Laryngoscopy and intubation
glasso-pharangeal nerve and from tracheo-bronchial tree via
the vagus nerve which enhances the activities of the
cervicalsympatheticafferentfibersresultingintransientrisein
heartrateandbloodpressure.
c.Light anaesthesia
Duringlightplanesofanaesthesiafeelingofpain,inadequate
sleep,amnesiaormusclerelaxationresultsinstressresponse
Pain
Thesuperficiallayeroftheskinisdenselysupplied-pain
nerveendings
Such pain characterized by both peripheral and central
sensitization.
Peripheralsensitization-damagedtissuesevokethetypical
localinflammatoryresponse.
The release of the traditional inflammatory mediators like
cytokine, leukotrienes, nerve growth factor, histamine,
serotonin, kallikrenin, protaglandins etc. increase the
sensitivityofnociceptors.
Centralsensitization-Thehighintensitypainsensationis
carriedthroughthefinelymyelinatednociceptivefibres.
A delta & smaller fibres cutaneous nerve fibres pass
throughthelamina,
where the change in the excitability of neurons in the
spinalcordistriggeredbytheafferentimpulses.


The exaggerated pain sensation affects the ascending
reticular,limbicsystem,thalamusandhypothalamus
whichregulatestheautonomic,neuroendocrineresponseby
stimulating the hypothalamic-pituitary-adrenalsympathetic axis
resultinginreleaseofallcatabolicandanabolichormones,
beforereachingthecortex.
Thepainsensationcausingsympatheticstimulationevenin
deeperplanesofanaesthesiaduringskinincision(e.g.rise
inheartrateandbloodpressureduringsternotomy).
Surgery:-Thestressresponsedependsontheextentof
injury.
The procedures of short duration, minimum tissue handling
evokeonlyaslightresponse.
The major procedures elicit more pronounced response -
which the flow phase may last up to several days or
weeks.

This results in excessive weight loss, also delays the

recovery,andambulationresultinginincreasedmorbidityand
mortality
WOUND
Tissueinjuryduringsurgicalincisionandtissuehandling,
activatesinflammationandhostdefencesystem
Quantity of the mediators and spill over of these
mediatorsaffectstheneuroendocrinereflexes.
Releaseofthemediatorsubstances,suchasinterleukinI
(IL-I) & tumor necrosis factor (TNF) from various cells
stimulatetheneuro-immuneaxisreleaseofthehormones
suchasACTH.

THE STRESS RESPONSE IS

DIVIDED IN TO TWO PHASES
SHOCK PHASE
very transient and
characterized by a
hypodynamicstate
Reduction in
metabolic rate &
depression of most
of the physiologic
processes.

FLOW PHASE
Hyper dynamic phase - last for
fewdaystoweeks
Flow phase corresponds to the
period of compensation, -increase
in metabolic rate, enzyme
modulation directed to glucose
production &consequent restitution
ofbloodvolume&stimulationof
theimmunesystem.
If the compensatory system
prevails, energy expenditure
diminishes and metabolism shifts
toanabolicpathways
STRESS HORMONES

reflexneuroendocrineresponsetotheinjuryisconsidered
asautocrines,endocrinesandparacrines.
Autocrines (Autonomic response) Catecholamines, insulin
andglucagon
Theplasmacatecholaminesincreaseimmediatelyafterinjury
&achievepeakconcentrationin24to48hoursdepending
ontheseverity.
This exerts metabolic, hemodynamic and hormone
modulatingactions.
Epinephrine causes hepatic glycogenolysis, gluconeogenesis,
lypolysis in the adipose tissues, ketogenesis increased
insulinresistance,preventingglucoseuptakebycells.
The direct cardio-respiratory effect increases heart rate,
myocardialcontractility,bloodpressureandrespiratoryrate.

GLUCAGON
The glucogan release is modulated by plasma
glucose, amino acid concentration, ANS and CNS
activities.
Glucagon along with catecholamine and cortisol
promotesandprolongstheliverglycogenesis.
It does not exert its effect during acute
hyperglycemia.
INSULIN
Theplasmaconcentrationofinsulinduringstresshas
beennotedtobebiphasic,
characterizedbythesuppressionofinsulinsecretion
followedbyanormalsecretion,
whichhasbeentermedasthephaseofphysiologic
insulinresistance.

ENDOCRINES
Hormonesunderhypothalamicpituitarycontrollikecortisol,
thyroxine,AVP,growthHormone.
Cortisol
Thecentralkeyistheexcitationofthehypothalamusduring
stressresultinginthesecretionofACTH
whichinturninitiatessuddenincreaseincortisollevel
Themetaboliceffectsofcortisolaredirectedtoovercome
thestressfulstate.
Thereisadirectfeedbackmechanismforcortisoltoboth
hypothalamus and pituitary gland to decreasethe
concentrationofcortisolinplasma
the potent stress stimuli always initiates either periodic
exacerbations of cortisol secretion at multiple times during
thedayorprolongedcortisolsecretionduringchronicstress.

Cortisolhaswidespreadeffectsonthemetabolism&
utilizationofglucose,aminoacidandfattyacidsin
hepaticandextra-hepatictissues.
Thecortisolcausesrapidmobilizationofaminoacids
and fat from their cellular stores, making them
immediately available both for energy and synthesis
of other compounds including glucose needed by
differenttissues
EFFECT OF CORTISOL ON
GLUCOSE METABOLISM
Thecortisolandotherglucocorticoidshave theabilitytostimulate
gluconeogenesisbyliverasmuchas6to10foldsduringstress.

Oneofitseffectisincreaseinglycogenstorageinthelivercells
whichistheprimarysourceofglucoseproduction.
The glucose production during flow phase is mediated through
glucagon and insulin using amino acids, lactates, pyruvates and
glyceroletc.
Cortisol mobilizes amino acids from the extra-hepatic tissues and
convertsitintoglucose.
Italsodecreasesanddelaystherateofglucoseutilizationinspite
ofincreasedinsulinsecretion,bloodglucoseconcentrationincreases
upto50%ofthenormal.
Excessofglucoseprovidesareadysourceofenergytoobligate
tissuessuchasCNS,woundandredcells,sincethesecellsdo
notrequireinsulinforglucosetransportandutilization.
PROTEIN METABOLISM
Cortisolmobilizesaminoacidsfromtheextrahepatic
cells&diminishingthetissuestores.
Increase in catabolism and decreased protein
synthesis
ResultsInthinningandweaknessofmuscles.
Incontrast,liverincreasestheformationofessential
plasmaproteinsandglucose.
FAT METABOLISM
Cortisolhelpsinmobilizationoffattyacidsfromthe
adiposetissues
Italsoincreasesoxidationoffattyacidsinthecells,
changingthemetabolicsystemofthecellsintimes
ofstarvationorstressfromutilizationofglucosefor
energy.
Ketogenesisdependsontheseverityofinjurybutis
suppressedbythehighinsulinlevel.
DuringinjurytheperipheralconversionofT4toT3
isimpaired.
TheplasmaconcentrationoffreeandtotalT3are
decreasedafterinjury
GROWTH HORMONE
The secretion of growth hormone is governed by
hypothalamicfactors,
autonomicstimulationandnon-hormonalsignals.
TheprimarymetabolicactionofGHduringstressis
topromoteproteinsynthesisandenhancelipidbreak
down,andglucosestores.
ARGININE VASOPRESSIN

Secretion of AVH is increased after major trauma,
hemorrhage,sepsis,pain.
ImmediateAVHrelease,followingacutereductionof
circulatingvolume,
It is a complex event acting through afferents
including baro, chemoreceptors and left atrial
receptors.
The preservation of water and sodium reduction in
the urine volume occurs as a compensatory
phenomenon.

ALDESTERONE
ACTH and angiotensin increases and stimulates
aldesteroneconcentrationfollowinginjury.
The primary aldesterone secretion is related to
sodium and water resorption from the distal
convolutedtubules
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.

PARACRINES
Theactivatedlocaltissue,vascularendothelialcellsystem
andsinglecellinitiatesresponseduringhemorragesepsis
inflammationandotherformofinjury.

It releases the cell derived mediator likes cytokine,

leukotrines, prostaglandins, histamine, serotonin, TNF,
interleukin I, II, VI, plasminogen activator, ecisanoids,
kallikreins-kininsandothermediators.
Thesemediatorsarealsoreleasedasaconsequenceof
cellinjuryordeathwhichhavedirecteffectontheANS
and CNS on the classical hormone system releasing
cortisol,EPandNEandotherstresshormonesinsmall
quantity.
Some mediators affect the vascular, metabolic,
coagulation,angiotensinandimmunologicalsystem.
The preventive measures for the release of such
mediators may play an important role in reducing the
stresshormones
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 shown
an increase -susceptibility infection through a significant
decrease in - cytotoxic activity of the natural killer cells.