IP100 CVS Disease (2) KS 2013 B&W

9/09/13
Objec;ves
Topic 4
Describesomeofthecauses,riskfactors, pathophysiologyandclinicalmanifesta;onsof thefollowingdiseases:

Heartfailure Aneurysm Arteriosclerosisandatherosclerosis Coronaryarterydisease
Cardiovascular Disease II
Kate Smith
K.F.Smith@curtin.edu.au

IP100Introduc;ontoPathophysiology
Describethepathogenesisofthrombosisand embolism OutlinetheprocessesinvolvedduringcloJng

FacultyofHealthSciences
HEARTFAILURE
Heartfailureriskfactors
Acomplexclinicalsyndrome Heartisincapableofmaintaininga cardiacoutput Leadstoinadequateperfusionof;ssues or, IncreaseddiastolicllingpressureofLV Resultsinincreasedpulmonarylling pressures

Hyperlipidemia Hypertension Diabetes Insulinresistance Highsaltintake Cardiomyopathy Smoking

Heartfailurecauses
HFtermstounderstand
Coronaryarterydisease Hypertension Heartvalvedisease Toxicinjury(virus,alcohol,drugsetc) Unknown(20%) Rarecasespregnancy

Preload AZerload Myocardialcontrac;lity Cardiacoutput Ejec;onfrac;on
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SystolicHeartFailure
Le#sidedHeartFailure
Inabilityofthehearttogenerateoutput sucienttoperfuse;ssues
Renalperfusiondecreases Ac;va;onofRAAS
Strokevolumedependenton:
Contrac;lity Preload AZerload
Contrac;lityreduced,egMI:
Ventricularremodellingresultsindisrup;on ofstructure Consequentdila;onofmyocardium SVdecreases,LVEDVincreases
IncreasedaZerload,egHTN,aor;cvalve disease
Resistancetoventricularemptying Increasedwork Hypertrophy MediatedbyangiotensinII
Preloadincreases
Toomuchstretch
ViciousCycle
LeZsidedHeartFailureconsequences
Decreasingcontrac;lity Increasingpreload IncreasingaZerload
Signs&symptoms
Shortnessofbreath Cough Decreasedurineoutput Fa;gue
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HeartFailure
Management
DRUGS!
Inotropestoincreasecontrac;lity Diure;cstoreducepreload ACEinhibitorstoreduceaZerload
DiastolicHeartFailure
Systolicfunc;onpreserved Pulmonaryconges;ondespitenormalSV& CO Inotropicdrugsnotindicated
RightsidedHeartFailure
RightsidedHeartFailure Inabilityofrightventricletoprovideadequate bloodowintopulmonarycircula;on IntheabsenceofleZheartfailure,abributed tohypoxicpulmonarydisease,eg

COPD Cys;cbrosis ARDS
RightsidedHeartFailure
Hypoxaemia Reexvasoconstric;onofpulmonary capillaries Narrowingofvessels Pulmonaryhypertension IncreasedrightventricularaZerload Failure(corpulmonale)

9/09/13
RightsidedHeartFailureconsequences
RightvsLeZHeartFailure
Signs&symptoms:
Swollenankles Liverfailure Weightloss
NewYorkHeartAssocFunc;onalClassica;onScale
ClassI: Nosymptomswithordinaryac;vity ClassII:Slightlimita;onofphysicalac;vity. Comfortableatrest,butordinaryphysicalac;vity resultsinfa;gue,palpita;on,dyspnoea,orangina ClassIII:Markedlimita;onofphysicalac;vity. Comfortableatrest,butlessthanordinaryphysical ac;vityresultsinfa;gue,palpita;on,dyspnoea,or anginapain ClassIV:Unabletocarryoutanyphysicalac;vity withoutdiscomfort.Symptomsofcardiacinsuciency maybepresentevenatrest
ANEURYSM Deni;on:localiseddila;onoroutpouching ofavesselwallorcardiacchamber Areaofweakness&vulnerability Forma;onisduetodisrup;onofthevessel wall Atherosclerosisisthemostcommoncauseof arterialaneurysms HTNincreasesstressonthewall Aortasuscep;ble
Aneurysm
Aneurysms
Trueaneurysms
Fusiformcircumferen;al Saccular Morelikelytoburst
Falseaneurysms
Extravascularhaematoma Morelikelytodissect
vascularweb.org
9/09/13
Aneurysm
Aneurysm
drstandley.com
www.aneurysmsymptoms.net
Cerebralaneurysm
ARTERIOSCLEROSIS Arteriosclerosisis...
Chronicdiseaseofthearterialsystem characterisedbyabnormalthickening&hardening ofthevesselwalls
drugster.info
Vesselsandinjury
VesselsandInjury
Vesselsmadeupof3layers:
Tunicain;ma(endothelialcells) Tunicamedia Adven;;a
Arteriosclerosis=hardeningofarteries Atherosclerosisisthepathologicalprocess
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Atherosclerosis
Pathophysiology InjuryInamma;on Frankinjury:

Toendothelialcells
SoZdepositsofintraarterialfat&brininthe vesselwallsthathardenwith;me Causesocclusiontobloodow Leadingcauseofcoronaryartery& cerebrovasculardisease
Injuriousenvironment:
Smoking,hypertension,diabetes,increasedLDL& decreasedHDLcholesterol Also:elevatedCreac;veprotein,increasedserum brinogen,insulinresistance,oxida;vestress, infec;on,periodontaldisease
ATHEROSCLEROSIS
ANTITHROMBOTICS INJURY INFLAMMATION VASODILATION
CORONARYARTERYDISEASE
MACROPHAGE FOAMCELLS FATTYSTREAK FIBROUSPLAQUE
Anyvasculardisorderthatnarrowsor occludesthecoronaryarteries Mostcommonisatherosclerosis CADmyocardialbloodsupply ischaemiaacutecoronarysyndromes infarc;on(irreversiblemyocardialdamage)
COMPLICATEDPLAQUE
EMBOLIS
CADRiskFactors
Atherosclerosisintherestofthebody
HTN Smoking Diabetesmellitus Obesity/sedentarylifestyle IncCreac;veprotein Hyperhomocysteinemia Infec;on

Anyvessel Supplyofbloodtoimportantareassuchas
Heart Brain Kidney Lungs Liver Limbs
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THROMBOSIS&EMBOLISM Slowbloodowistheenemy! Roughening,trauma,infec;on,obstruc;onor inamma;onofthein;mal/endothelium surface Ac;vatescloJngcascade Shockcanini;atecoagula;onpathways
Thrombus
rejuvenal.info
Thrombosis
Embolism
Embolus=abolusofmabercircula;nginthe bloodstreame.g.dislodgedthrombus,anair bubble,afatball,bacteria,cancercells, foreignsubstances Embolism=theobstructedvessel Embolusistransportedinbloodstreamun;lit reachesavesselthatitistoonarrowtot through

www.the-hospitalist.org/.../2009_05_pp21_01.jpg
EmbolismandEmbolus
ConsequencesofEmbolism
Ischemia Infarc;on Necrosis Organdysfunc;on Pain Where:lungs,heart,brain,kidney,liver, gut,limbs...

lockyep.blogspot.com
9/09/13
Haemostasis
PlateletFunc;ons
Arrestofbleeding Threecomponents:
1. Platelets 2. Bloodproteins(cloJngfactors) 3. Vasculature(endothelialcells&subendothelial matrix)
1. Contributetoregula;onofbloodowintoa damagedsitethroughinduc;onof vasoconstric;on 2. Ini;ateinterac;onsresul;nginforma;onof plateletplug 3. Ac;vatecloJngcascadetostabiliseplatelet plug 4. Ini;aterepairprocesses

PlateletAc;va;on Plateletsac;vatedwhenavesselisdamaged Ac;va;onproceedsthrough:

Adhesion Aggrega;on Ac;va;on
CloJng ThecloJngsystemisagroupofplasma proteinsthat,whenac;vatedsequen;ally, formabloodclot Abloodclotisameshworkofproteinstrands (brin)thatstabilisestheplateletplug&traps othercells Clots:

Plugdamagedvessels Trapmicroorganisms Provideaframeworkforhealing
Ac;vatedplateletscauseaplateletplugto sealtheinjuredendothelium Ifdamageisminor,haemostasisisachieved Abloodclotstabilisestheplateletplug

CloJng
CloJng
Complexsystemwiththreebasicsteps:
1. ReleaseofcloJngfactorsfrominjured;ssue cells&s;ckyplatelets 2. Seriesofchemicalreac;onsresul;nginthe forma;onofthrombin 3. Forma;onofbrin&trappingofbloodcellsto formaclot
Processusuallypresentedastwopathwaysof ini;a;on
1. Intrinsic(;ssuefactor) 2. Extrinsic(contactac;va;on)
thatjoininacommonpathway
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CloJng
1.IntrinsicPathway
Pathwaysac;vatedbymanysubstances releasedduring;ssueinjury&infec;on,eg
Collagen Proteinases Kallikrein Plasmin Bacterialproducts,egendotoxins
Contactac;va;onpathway Ac;vatedinthepresenceofanabnormalor damagedvesselwall Hagemanfactor(factorVII)inplasmacontacts subendothelialsubstancesexposedby vascularinjury
2.ExtrinsicPathway
CommonPathway
Tissuefactorpathway Tissueinjury Membraneboundorsoluble;ssuefactor (;ssuethromboplas;n)isreleasedby damagedendothelialcellsinbloodvessels Reactswithac;vatedfactorVII(VIIa)
BothpathwaysconvergeatfactorX(Stuart Prowerfactor) Ac;va;onoffactorXbeginsthecommon pathway:

Prothrombinisconvertedtothrombin Thrombinconvertsbrinogentobrin Fibrinpolmerisestoformaclot
Tutorial&Lab
CommonwealthofAustralia
Copyright Regulations 1969
Tutorial:
Ques;onsthatleadyoutoexploretherole ofinamma;oninthepathophysiologyof atherosclerosis Usep.594onwardsfromyourtext
WARNING Thismaterialhasbeencopiedandcommunicatedtoyoubyor onbehalfofCur;nUniversityofTechnologypursuanttoPart VboftheCopyrightAct1968(theAct). Thematerialinthiscommunica;onmaybesubjectto copyrightundertheAct.Anyfurthercopyingor communica;onofthismaterialbyyoumaybethesubjectof copyrightprotec;onundertheAct. Donotremovethisno;ce
Lab:
ECGs&BP

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9/09/13

Describesomeofthecauses,riskfactors, pathophysiologyandclinicalmanifesta;onsof thefollowingdiseases:

Describethepathogenesisofthrombosisand embolism OutlinetheprocessesinvolvedduringcloJng

Acomplexclinicalsyndrome Heartisincapableofmaintaininga cardiacoutput Leadstoinadequateperfusionof;ssues or, IncreaseddiastolicllingpressureofLV Resultsinincreasedpulmonarylling pressures

Hyperlipidemia Hypertension Diabetes Insulinresistance Highsaltintake Cardiomyopathy Smoking

Coronaryarterydisease Hypertension Heartvalvedisease Toxicinjury(virus,alcohol,drugsetc) Unknown(20%) Rarecasespregnancy

Preload AZerload Myocardialcontrac;lity Cardiacoutput Ejec;onfrac;on

Decreasingcontrac;lity Increasingpreload IncreasingaZerload

Inotropestoincreasecontrac;lity Diure;cstoreducepreload ACEinhibitorstoreduceaZerload

Systolicfunc;onpreserved Pulmonaryconges;ondespitenormalSV& CO Inotropicdrugsnotindicated

RightsidedHeartFailure Inabilityofrightventricletoprovideadequate bloodowintopulmonarycircula;on IntheabsenceofleZheartfailure,abributed tohypoxicpulmonarydisease,eg

Hypoxaemia Reexvasoconstric;onofpulmonary capillaries Narrowingofvessels Pulmonaryhypertension IncreasedrightventricularaZerload Failure(corpulmonale)

Pathophysiology InjuryInamma;on Frankinjury:

SoZdepositsofintraarterialfat&brininthe vesselwallsthathardenwith;me Causesocclusiontobloodow Leadingcauseofcoronaryartery& cerebrovasculardisease

MACROPHAGE FOAMCELLS FATTYSTREAK FIBROUSPLAQUE

Anyvasculardisorderthatnarrowsor occludesthecoronaryarteries Mostcommonisatherosclerosis CADmyocardialbloodsupply ischaemiaacutecoronarysyndromes infarc;on(irreversiblemyocardialdamage)

HTN Smoking Diabetesmellitus Obesity/sedentarylifestyle IncCreac;veprotein Hyperhomocysteinemia Infec;on

THROMBOSIS&EMBOLISM Slowbloodowistheenemy! Roughening,trauma,infec;on,obstruc;onor inamma;onofthein;mal/endothelium surface Ac;vatescloJngcascade Shockcanini;atecoagula;onpathways

Embolus=abolusofmabercircula;nginthe bloodstreame.g.dislodgedthrombus,anair bubble,afatball,bacteria,cancercells, foreignsubstances Embolism=theobstructedvessel Embolusistransportedinbloodstreamun;lit reachesavesselthatitistoonarrowtot through

Ischemia Infarc;on Necrosis Organdysfunc;on Pain Where:lungs,heart,brain,kidney,liver, gut,limbs...

1. Contributetoregula;onofbloodowintoa damagedsitethroughinduc;onof vasoconstric;on 2. Ini;ateinterac;onsresul;nginforma;onof plateletplug 3. Ac;vatecloJngcascadetostabiliseplatelet plug 4. Ini;aterepairprocesses

PlateletAc;va;on Plateletsac;vatedwhenavesselisdamaged Ac;va;onproceedsthrough:

CloJng ThecloJngsystemisagroupofplasma proteinsthat,whenac;vatedsequen;ally, formabloodclot Abloodclotisameshworkofproteinstrands (brin)thatstabilisestheplateletplug&traps othercells Clots:

Ac;vatedplateletscauseaplateletplugto sealtheinjuredendothelium Ifdamageisminor,haemostasisisachieved Abloodclotstabilisestheplateletplug

Contactac;va;onpathway Ac;vatedinthepresenceofanabnormalor damagedvesselwall Hagemanfactor(factorVII)inplasmacontacts subendothelialsubstancesexposedby vascularinjury

Tissuefactorpathway Tissueinjury Membraneboundorsoluble;ssuefactor (;ssuethromboplas;n)isreleasedby damagedendothelialcellsinbloodvessels Reactswithac;vatedfactorVII(VIIa)

BothpathwaysconvergeatfactorX(Stuart Prowerfactor) Ac;va;onoffactorXbeginsthecommon pathway:

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