HD1Pathology

AtherosclerosisandIschemicHeartDisease
I) Atherosclerosis
A) Generalproperties
1) Apathologicchangethataffectslargeandmediumsizedarteries
2) Characterizedbyintimallesionscalledatheromas(oratheromatousplaques)
(a) Theseareraisedlesionscoveredbyawhitefibrouscapandcontainingasoft,yellow,lipidcore
3) Canobstructbloodflow,rupture,calcify,and/orweakentheunderlyingmedia

B) Riskfactorsforatherosclerosis

Major

Lesser,Uncertain,
orNonquantitated

RiskFactorsforAtherosclerosis
Nonmodifiable
Increasingage
Malegender
Familyhistory
Geneticabnormalities
Obesity
Physicalinactivity
Stress
Postmenopausalestrogendeficiency
Hardened(trans)unsaturatedfatintake

Potentiallycontrollable
Hyperlipidemia
Hypertension
Cigarettesmoking
Diabetes
Highcarbohydrateintake
Alcohol
LipoproteinLp(a)
Chlamydiapneumoniae

1) Hypercholesteremiaasamajorriskfactor
(a) LDL(badcholesterol)deliverscholesteroltoperipheraltissues
(b) HDL(goodcholesterol)recyclescholesteroltotheliverforexcretion
2) Inflammationasariskfactor
(a) Creactiveprotein,anacutephasemolecule,isausefulmarkerofriskforatherosclerosisand
ischemicheartdisease
C) Pathogenesis
1) Endothelialinjuryordysfunctionproducesathrombogenicand/oradhesivecellsurface
2) Adhesionofplateletsandmonocytes,whichreleasegrowthfactors
3) Smoothmusclecellsmigratetothedysfunctionalsiteandproliferate
4) Smoothmusclecellsproducecollagen,proteoglycans,andotherECMconstituents
5) Macrophagesdigestlipid(e.g.LDL)andbecomefoamcells
D) Stagesofatheromatousplaques
1) Fattystreak
(a) Earlylesions(mayevenbeobservedinchildrenandadolescents)
(b) Oftenappearatbranchpointswhereflowismoreturbulent
2) Fibrofattyplaque
3) Advancedplaque
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(a) Stableplaque
(b) Vulnerableplaque
4) Complicatedplaque
(a) Mostseriousstage
(b) Oftenhaveoverlyingthrombithatmyhaveruptured
(c) Calcificationsinthenecroticcentersarecommon
E) Complicationsofatheromas
1) Stenosis(especiallyofsmallarteries)
2) Ulcerationoffibrouscapthrombosisatheroembolism
3) Intraplaquehemorrhage
4) Aneurysmformation
5) Calcification
II) IschemicHeartDisease
A) Anginapectoris
1) Chestpainresultingfromischemiawithoutfrankinfarction
2) Threeclinicalpatternsofangina
(a) Stablecausedbystenosisofmajorcoronaryvessels
(b) Prinzmetalcausedbyvasospasm
(c) Unstablecausedbyplaquedisruptionwithvariablemuralthrombi
B) Myocardialinfarction(MI)
1) Leadingcauseofdeathindevelopednations
2) Distributionofinfarctsbyvesselinvolvement
(a) Leftanteriordescendingartery
(i) Anteriorwallofleftventricle
(ii) Anteriorpartofinterventricularseptum
(b) Rightcoronaryartery
(i) Posteriorwallofleftventricle
(ii) Posteriorpartofinterventricularseptum
(c) Circumflexartery
(i) Lateralwallofleftventricle
3) MacroscopicdatingofMI
(a) Appearsnormalupto8hourspostMI
(b) Appearsmottledafter8hours
(c) Appearsyellowwitharededgeafter36hours
(d) Slightshrinkageisobservedafter1week
(e) Thinningisobservedafter3weeks
(f) Scarringisobservedafter68weeks
(g) Adensescarisformedafter3months
4) MicroscopicdatingofMI
(a) 412hourscoagulativenecrosisandedema
(b) 1224hoursnuclearpyknosis,increasedeosinophilia,neutrophilsatborder
(c) 13dayslossofstriationsandnuclei,neutrophilsinvade
(d) 37dayslossofmyocytes,neutrophilsvanish,histiocytesappear
(i) Itisduringthisperiodthatthemyocardiumismostvulnerabletorupture
(e) 710daysphagocytosis,earlygranulationtissue
(f) 1014daysadvancedgranulationtissue
(g) >2monthsdensescar
5) ResultsandcomplicationsofMI
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(a) Nocomplications(1020%)
(b) Cardiacfailure(60%)
(i) Arrhythmias,heartblock,suddendeath
(c) Cardiogenicshock(10%)
(d) Muralthrombusandembolism(1540%)
(e) Rupture(15%)
(f) Cardiacaneurysm
(g) Fibrinouspericarditis(Dresslersyndrome)
III) ReperfusionandReperfusionInjury
A) Reperfusion
1) Reperfusioncanbeaccomplishedbythrombolysisorplacementofastent
2) Earlierreperfusionisassociatedwithbetteroutcomes
(a) Reperfusionwithin20minutesusuallypreventsnecrosis
(b) Reperfusionwithinthefirst34hoursiscritical,asreperfusionafterthistimewillfailtolimitthe
sizeoftheinfarct
3) Reperfusedmyocardiumishemorrhagic
4) Contractionbandsareseeninirreversiblyinjuredmyocytesduetoexaggeratedcontractionofcells
duringreperfusion(duringwhichtheyareexposedtohighconcentrationsofcalcium)
B) Reperfusioninjury
1) Fourtypes
(a) Stunnedmyocardium
(b) Impedanceofmicrovascularbloodflow(noreflowphenomenon)
(c) Reperfusionarrhythmias
(d) Lethalreperfusioninjury
(i) Independentmediatorofcardiomyocytedeath
(ii) Causes
o Increasedintracellularcalcium
o ROS
o pHchanges
o Inflammation
(iii)
Mediatescardiomyocytedeathbyopeningmitochondrialpermeabilitytransitionpores
(PTPs)andinducingmyocardialhypercontracture
PatternsofPulmonaryInjuryI
I) Atelectasis
A) Definition
1) Collapse(orincompleteexpansion)ofpartorallofthelung
B) Severaltypesdependingontheirmechanismofcollapse
1) Resorptiveresultsfromobstructionofairway
(a) Secretions
(b) Aspirationofforeignbodies
2) Compressiveresultsfromexternalcompressionofalveoli
(a) Hydro,pneumo,hemothorax
(b) Exudateinpleuralcavity(pleuraleffusion)
(c) Tumor
II) PulmonaryEdema
A) Definition
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1) Buildupoffluidinthealveoli
B) Numerouscauses
1) Increasedhydrostaticpressureinpulmonarycapillaries
(a) Leftheartfailure
(b) Mitralstenosis
(c) Increasedbloodvolume
(d) Pulmonaryveinobstruction
2) Decreasedoncoticpressureinpulmonarycapillaries
(a) Hypoalbuminemia
(b) Nephroticsyndrome
(c) Liverdisease
(d) Proteinlosingenteropathies
3) Pulmonarymicrovascularinjury
(a) Infection
(b) Aspirationofforeignbody
(c) Drugs
(d) Radiation
(e) Trauma
C) Twotypes,dependingoncardiacinvolvement
1) Cardiogenic,whereheartpathologyprecipitatespulmonaryedema
2) Noncardiogenic,whereotherpathologiesprecipitatepulmonaryedema
III) DiffuseAlveolarDamage
A) Definition
1) Histologicalpatternoflunginjuryseeninacuterespiratorydistresssyndrome
B) Mechanism
1) Injurytopneumocytesandendothelialcellsismediatedbyseveralfactors
(a) Activationofneutrophilsandmacrophages
(i) Releaseofproinflammatorycytokines(IL8,IL1,andTNF)recruitneutrophilstothe
alveolarspace
(ii) Activatedneutrophilssubsequentlyreleaseproteasesandleukotrieneswhichcontributeto
localtissuedamage
(b) Chronicinflammationandimbalanceofpro/antiinflammatorymediators
(c) Lossofsurfactant
C) Numerousetiologies
1) Infections
2) Physicalandchemicalinjury
3) Hematologicconditions
4) Medical/surgicalconditions(e.g.transfusionassociatedlunginjury,TRALI)
D) Phases
1) Exudative
2) Proliferative(<50%survivalrateoncethisstageisreached)
IV) ChronicObstructivePulmonaryDisease
A) Definition
1) Constellationofpathologiesthathindertheabilitytoexhaleairefficiently
B) Compositepathologies(discussedinfurtherdetailbelow)
1) Emphysema
2) Chronicbronchitis/bronchiolitis
3) Bronchiectasis
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4) Bronchialasthma
V) Emphysema
A) Definition
1) Destructiveenlargementofairspacesdistaltotheterminalbronchioles
B) Fourtypes
1) Centriacinaremphysema
(a) Destructionofthecentralportionofthefunctionalacinuswithsparingofdistalairways
(b) Upperlobesaretypicallyaffectedmoreseverely
(c) Associatedwithsmoking
2) Panacinaremphysema
(a) Uniforminjuryacrossthediseasedregion
(b) Lowerlobesaretypicallyaffectedmoreseverely
(c) Associatedwithsmokingand1antitrypsindeficiency
3) Paraseptalemphysema
(a) Areasoffibrosisandatelectasisarefoundadjacenttothepleura
(b) Morefrequentlyaffectstheupperlobes
4) Irregularemphysema
(a) Injuryisobservedadjacenttoareasoffibrosis

C) Pathogenesis
1) SmokingdamagesthelungsthroughthegenerationofROSandalterationofproteaseactivity

2) Tissuedamagehasseveralendresults
(a) Lossofelasticrecoil(dueinparttoneutrophilelastase)
(b) Inflammation
(c) Gobletcellmetaplasiamucusplugging
(d) Thickeningofthebronchiolarwall
VI) ChronicBronchitis/Bronchiolitis
A) Definition
1) Persistentcoughwithsputumproductionforatleast3monthsinatleast2consecutiveyears
B) Causes
1) Smokinganddustirritatetheairwaysinflammation,squamousmetaplasia,andinjurytocilia
VII) Bronchiectasis
A) Definition
1) Dilationofbronchiandbronchiolessecondarytochronicinflammation
B) Associatedconditions
1) Obstruction
2) Cysticfibrosis
3) Ciliopathies
(a) Kartagenersyndrome,wherecilialackdyneinarms
4) Necrotizingpneumonia
VIII) BronchialAsthma
A) Definition
1) Chronicinflammatorydisorderoftheairwaysthatresultsincontractionofbronchialmuscle
B) Types
1) Extrinsic(atopic,allergic)
(a) MediatedbyIgEasatypeIhypersensitivityreaction
(b) IgEandmastcellsrecruiteosinophils,whichpromotesmoothmusclecontraction
2) Intrinsic(nonatopic)
(a) Noallergensensitization
LungCancer
I) OverviewofLungCancer
A) Epidemiology
1) Leadingcauseofpreventabledeath
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B)

C)

D)

E)

F)

G)

2) ThirdmostcommonmalignancyintheUS,butmostfrequentlethalcancer(~29%ofallcancer
deaths)
Riskfactors
1) Smoking(includingsecondhandsmoke)
2) Geneticpredisposition
(a) CYP1A1polymorphisms
(b) GlutathioneStransferase(GSTM1)polymorphisms
3) Radongas
4) Asbestos
5) Airpollutants
6) Viruses(e.g.HPV,JCV,SV40,CMV,etc.)
7) Radiation
Oncogenicmutations
1) Krasprotooncogene
(a) Observedin2030%ofnonsmallcelllungcancers
2) Epithelialgrowthfactorreceptor(EGFR)gene
3) ALK(anaplasticlymphomakinase)translocations
(a) Associatedwithnonsmallcelllungcancersinlightandnonsmokers
Clinicalpresentation
1) Earlycancerisasymptomatic,makingearlydetectiondifficult
2) Advancedtumorsareassociatedwithseveralsymptoms
(a) Recurrentpneumonia
(b) Dyspnea
(c) Coughingandhemoptysis
(d) Weightloss
3) Specialpresentations
(a) Paraneoplasticsyndromes
(b) Superiorvenacavasyndrome(obstructionofSVC)
(c) Pancoasttumor(tumoratveryapexoflung)
(d) Hornerssyndrome(sympatheticsymptomsofptosis,miosis,ahidrosis,etc.)
Diagnosis
1) Imaging(CXR,CT,PETCT,bonescans,etc.)
2) Tissuesampling
(a) Bronchialbrushing/washing
(b) Bronchioalveolarlavage
(c) Biopsy
Metastasis
1) Lymphaticspreadhilarlymphnodesmediastinallymphnodes
(a) Mediastinalnodeinvolvementisastrongmarkerofdistantspreadandpoorsurvival
2) Residentsites
(a) Bone
(b) Brain
(c) Liver
(d) Adrenalglands
Classifications
1) Therapeuticclassifications
(a) Smallcelllungcarcinoma(unresectable)
(b) Nonsmallcelllungcarcinoma(resectableatearlystages)
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(c) Metastaticcarcinomas(fromothersites)
2) Histologicclassification
(a) Adenocarcinoma(4050%)
(i) Bronchioalveolarcarcinoma(specialtypeofadenocarcinoma)
(b) Squamouscellcarcinoma(2030%)
(c) Largecellundifferentiated(510%)
(d) Smallcellcarcinoma(10%)
(e) Carcinoid
II) Adenocarcinoma
A) General
1) Malignantepithelialtumorswithseveralgrowthpatternsandmucusproduction
(a) Tubular
(b) Acinar
(c) Papillary
2) Mayappearasspiculated,starshapedlesionsonchestCT
3) Irregulargrowthpatterninvadeslung
B) Bronchioalveolarcarcinoma
1) Noninvasivetumorwithblandcytology
2) Maybeclassifiedasadenocarcinomainsitu
3) Types
(a) Mucinous
(b) Nonmucinous
III) SquamousCellCarcinoma
A) General
1) Malignantepithelialtumorwithmorphologicevidenceofkeratinizationand/orintercellularbridges
2) Highlylinkedtosmoking
IV) SmallCellCarcinoma
A) General
1) Malignantepithelialtumorconsistingofsmallcellswithseveralfeatures
(a) Minimalcytoplasm
(b) Finelygranularnuclearchromatin
(c) Absentorinconspicuousnucleoli
(d) Prominentnuclearmolding
(e) Highmitotic,apoptotic,andnecroticactivity
2) Highlyassociatedwithsmoking
3) Commonlycausesparaneoplasticsyndromes
(a) EctopicACTHsecretionCushingssyndrome
(b) InappropriateADHsecretion
(c) Encephalitis
B) Poorprognosis
1) Longtermsurvival<5%
2) Unresectable
V) CarcinoidTumors
A) General
1) Neuroendocrinetumorswithuniform,blandcytology
2) Allhavemalignantpotential
B) Typicalcarcinoid
1) <2mitoses/10HPF(highpowerfield)
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2) Nonecrosis
3) 5yearsurvivalrate>90%
C) Atypicalcarcinoid
1) 210mitoses/10HPF
2) Necrosis
3) 5yearsurvivalrateof5070%
D) Treatment
1) Surgicalresectionwithlymphnodedissection
MyocardialDiseaseandTumors
I) Cardiomyopathy
A) Fourtypes
1) Dilatedcardiomyopathy(DCM)
(a) Dilationofallfourheartchambers(especiallytheleftventricleandatrium)
(b) Impairmentofcontractilitysystolicdysfunction
(c) Causes
(i) Mostcasesareidiopathic
(ii) Alcoholismandmalnutrition
(iii)
Peripartum
(iv)Myocarditis
(v) Adriamycintherapy(DNAintercalatorusedforcancerchemotherapy)
o AcuteDCMwillresolvewhenadriamycintherapyisstopped
o ChronicDCMwillpersistregardlessofadriamycintherapy
(vi)Geneticmutationsincytoskeletalproteins(includingdystrophin)
(d) Diagnosticcriteria
(i) Positivecriteria(allfourmustbepresent)
o Generalizedhypertrophyanddilation(large,globularheart)
o Muralthrombi
o Endocardialthickening
o Myocardialfibrosis
(ii) Negativecriteria(noneofthesecanbepresent)
o Nomajorcoronaryarterydisease/anomaly
o Novalvulardiseaseoranomaly
o Nosystemichypertension
o Noshuntswithinoroutsidetheheart
(e) Histologicfindings
(i) Dark,enlargednucleiwithbluntedends(rectangularshape)
(ii) Hypertrophiccardiomyocytes
2) Hypertrophiccardiomyopathy(HCM)
(a) Hypertrophyoftheleftventriclewithleftatrialenlargement
(b) Impairmentofcompliancediastolicdysfunction
(c) Causes
(i) Almostexclusivelygenetic(mutationsinsarcomericproteins)
(d) Diagnosticfeatures
(i) Dynamicleftventricularoutflowobstructiontransientmurmur
o Theanteriorleafletofthemitralvalveslapsagainsttheventricularseptumfibrosisof
boththeleafletandseptalwall(mirrorimageplaque)stenosisandmurmur
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(ii) Dyspneaonexertion
(iii)
Ventricularenlargementcanbesymmetricorasymmetric(ASH)
(e) Histologicfindings
(i) Myocytehypertrophy
(ii) Myofiberdisarray
3) Restrictivecardiomyopathy(RCM)
(a) Mildhypertrophyoftheleftventriclewithleftatrialenlargement
(b) Impairmentofcompliancediastolicdysfunction
(c) Causes
(i) Idiopathic
(ii) Amyloidosis
o Cardiacamyloidosismayoccuraspartofsystemicamyloidosis(ALamyloidosis)
o Insolubleamyloidproteinisdepositedinbetapleatedsheets,whichbindcongoreddye
forvisualization(appeargreenwithluminescence)
(iii)
Radiationinducedfibrosis
4) Arrhythmogenicrightventriculardysplasia/cardiomyopathy(ARVCM)
(a) Hypertrophyoftherightventricularfreewallismostcommon(thoughleftventricularand
biventricularformsexist)
B) Channelopathies
1) Geneticmutationsthataffectmyocardialionchannels
2) Examples
(a) QTsyndrome
(b) Brugadasyndrome
3) Patientshaveelectricalabnormalitiesthatpredisposethemtosuddencardiacdeathfromfatal
arrhythmias
II) Myocarditis
A) Majorcausesofmyocarditis
1) Infections
(a) Viruses(e.g.,coxsackievirus,echo,influenza,CMV)
(b) Chlamydiae
(c) Rickettsiae
(d) Bacteria(e.g.,Corynebacteriumdiphtheria,Neisseriameningococcus,Borreliaburgdorferi)
(e) Fungi
(f) Protozoa
(g) Helminths
2) Immunemediatedreactions
(a) Postviral
(b) Poststreptococcal(rheumaticfever)
(c) SLE
(d) Drughypersensitivity
(e) Transplantrejections
3) Unknown
(a) Sarcoidosis
(b) Giantcellmyocarditis
B) Grossfindings
1) Thin,mottledventricularwall
C) Histologicfindings
1) Neutrophilinfiltration
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2) Isolatednecrosis
3) Granulomaformationwithgiantcells
4) Endstagefibrosiswithcollagendeposition
III) Tumors
A) Primarytumorsoftheheartarerare
1) Myxoma
(a) Mostcommonprimarytumorinadults
(b) Clinically,mimicmitralstenosisorinfectiveendocarditis
(c) Dangerofembolism
(d) Histologyrevealsspindleshapedmyxomacellsinagelatinousbackgroundthatgiveriseto
capillaryvessels
2) Rhabdomyoma
(a) Mostcommonprimarytumorinchildren
(b) Probablyhamartomas(malformations)
(c) Associatedwithtuberoussclerosis
B) Morecommonly,tumorsintheheartaremetastasesofothertumors
1) Breast
2) Lung
3) Lymphoma
4) Melanoma
LaboratoryDiagnosisofHeartDisease
I) CommonRiskBiomarkers
A) Riskfactorsforischemicheartdisease
1) ElevatedLDL(>100mg/dL)
2) LowHDL(<40mg/dL)
3) Cigarettesmoking
4) Hypertension(BP>140/90)
5) FamilyhistoryofprematureCHD
(a) Malefirstdegreerelative<55yearsold
(b) Femalefirstdegreerelative<65yearsold
6) Age
(a) Males>45yearsold
(b) Females>55yearsold
7) Obesity
8) Physicalinactivity
9) Poor(atherogneic)diet
10) ElevatedCreactiveprotein(CRP,>1.0mg/dL)
(a) Thepathologyofatherosclerosishasaninflammatorycomponent
(b) CRPisanonspecificmarkerofinflammationthatiselevatedinsubjectswithinflammation
(includingatherosclerosis)
(c) Twoassaysfordetection
(i) Generalassaywilldetecthighlevels
(ii) Highsensitivityassay(hsCRP)willdetectsubtleincreases
(d) StatintherapywasshowntobeeffectiveinpatientswithnormalLDLlevels,butelevatedCRP
II) MarkersofMyocardialInjury
A) Featuresofusefulbiomarkers
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1) Accurateandrepeatablemeasurementsareavailable
(a) Reasonablecost
(b) Rapidturnaroundtime
2) Provideinformationnotobtainablebyclinicalassessment
3) Knowledgeofthemeasuredlevelaidsclinicaldecisionmaking
B) Cardiactroponins(IorT)
1) Preferredlabmarkers
(a) Risewithin23hours
(b) Peakwithin24hours
(c) Remainelevatedfor1014days(dependsonassay)
2) Threeisoforms
(a) TnC(bindscalcium)
(i) Notcardiacspecific,andthusnotusedfordiagnosis
(b) TnI(inhibitsactin/myosininteractions)
(i) Cardiacspecific,andthusisusedfordiagnosis
(c) TnT(bindstropomyosin)
(i) Foundprimarilyinmyocytes,andmaybeusedfordiagnosis
(ii) Longerhalflife
(iii)
Risesinrenalfailure
(d) Recommendedtotestat0,6,and9hoursafterpresentation
3) Freecytolosicformsarereleasedfirst,andcomplexedformsarereleasedasnecrosispersists
4) Presenceofelevatedtroponinlevelsmayaltertreatmentcourse

C) Creatinekinase(CKorCPK)
1) Largelyreplacedbytroponintesting
2) DimerofMandBsubunits
D) Olderbiomarkers
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1)
2)
3)
4)

Increasedwhitecellcount
Myoglobin(risesandfallsearly)
Aspartateaminotransferase(AST)
Lactatedehydrogenase(flippedpattern)

III) MarkersofHeartFailure
A) Atrialnatriureticpeptide
1) Notused,duetoshorthalflife
B) Btypenatriureticpeptide(BNP)
1) Synthesizedbymyocytesandfibroblastsinresponsetodiastolicstretch
2) EffectsofBNP
(a) Inhibitssympatheticactivity
(b) Reducessecretionofsomehormones
(i) Renin
(ii) AngiotensinII
(iii)
Aldosterone
(c) Causesvasodilation
(d) Decreasesbloodpressure
(e) Increasessodiumandwaterexcretion
3) PhysiologicalvariationsinBNPlevels
(a) Age(increaseswithage)
(b) Sex(higherinfemales)
(c) BMI(DecreaseswithBMI)
4) Usedtoassessheartfailure
(a) Veryhighnegativepredictivevalue
(i) I.e.,anormalBNPlevelisastrongindicatorthatthepatientdoesnothaveheartfailure
ValvularHeartDisease
I) GeneralConcepts
A) Insufficiency
1) Valvedoesnotclosecompletely,allowingreverseflow
2) Alsocalledregurgitationorincompetence
B) Stenosis
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1) Valvedoesnotopencompletely,restrictingforwardflow
C) Somediseasesmayhavefeaturesofbothinsufficiencyandstenosis
D) Leftsidedvalvulardisordersaremuchmorecommon
II) AorticPathology
A) Degenerativeaorticvalvestenosis
1) Progressivecondition
(a) Depositionoflipoproteinschronicinflammationdystrophiccalcificationofvalvecusps
(b) Withseniletypecalcificaorticvalvestenosis,theindividualtypicallybecomessymptomatic
aroundage7080
2) Characteristics
(a) Scatteredcalcificnodulesandareasoffibrosisappear
(b) Mostprominentdamageoccursatthebaseofthevalvecuspsontheaorticside
3) Complications
(a) Leftventricularhypertrophy
(b) Aorticrootdilation
(c) Coronaryinsufficiency
(d) Mitralvalveannulardilation
(e) Heartfailure

B) Congenitalanomalies
1) Bicuspidaorticvalve
(a) Mostfrequentcardiovascularmalformationinhumans
(b) Mayhaveraphe
(i) Fibrousattachmentsbetweenthevalvecuspandtheaorticwallthatinsertslowerthanthe
commissure
2) Unicuspidaorticvalve
(a) Veryrare
(b) Thecentralholemaybeacommissural(doesnotextendtotheaorticwall)orunicommissural
(makesoneconnectiontotheaorticwall)

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3) Bicuspidandunicuspidaorticvalvespredisposetheindividualtodegenerativechangesatanearlier
age
(a) Calcificationsofbicuspidaorticvalvestypicallybecomesymptomaticaroundage5060
(b) Unicuspidaorticvalvestypicallybecomesymptomaticinchildhood(<15yearsofage)
III) MitralValveProlapse
A) Arelativelycommonconditioncharacterizedbyafloppymitralvalve
B) Threegroupsofpatientsaretypicallyaffected
1) Youngfemalesmayexperienceabenigncourse
2) Oldermenmayexperienceamoreaggressivecourserequiringsurgicalintervention
3) Oftenseeninpatientswithconnectivetissuedisorders(e.g.,MarfanSyndrome)
C) Characteristics
1) Theposteriorleafletisaffectedmostoften
(a) Moreseverecasesmayinvolvebothleaflets
2) Depositionofgelatinous(pseudomyxoma)materialcreatesahoodingeffect,wherethevalvecan
billowbackintotheleftatrium
(a) Chordaetendinaearealsoaffectedbythedepositionofthismaterial
3) Causesmitralinsufficiency
D) Clinicalfindings
1) PVCswithpalpitations
2) Midsystolicclickuponauscultation
3) Progressivemitralregurgitation
E) Complications
1) Riskfactorforbacterialendocarditis
(a) Vegetations(thrombiorbacterial)mayformonthevalveandembolize
2) Rupturedchordaetendinae
3) Arrhythmia(PVCs)
4) Suddendeath(rare)
IV) RheumaticHeartDisease
A) Mostcommoncauseofmitralstenosisworldwide
B) Rheumaticheartdiseaseisachronicpathologyaffectingthecardiacvalves,andoftendevelopsafter
multipleepisodesofacuterheumaticfever
1) Rheumaticfeverresultsfromanimmunemediatedhypersensitivityreactionfollowing
untreated/chronicgroupAstreptococcusinfection(e.g.,Streptococcuspyogenes)
(a) AppearstobetheresultofantigenicsimilaritybetweenbacterialMproteinsandhostmyocardial
tissues,causingthehosttoraiseantibodiesagainsthosttissue
2) Rheumaticfeverinvolvesallthreelayersoftheheart(endocarditis,myocarditis,andepicarditis)
C) Characteristicfeatures
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1) Fusionofthecommissuresfishmouthappearance

2) Fusionofchordaetendinae
3) Aschoffbodiesarediagnosticofrheumaticfever
(a) Regionsoffibrinoidnecrosissurroundedbylymphocytes,macrophages,plasmacells,and
occasionalgiantcells
(b) Containscaterpillarcells(orAnitschkowcells),macrophageswithawavynucleus
D) Complications
1) Mitralstenosisleftatrialdilation
2) Valvefibrosisanddeformity
3) Valvestenosisandinsufficiency
4) Ultimately,damagetothevalvesurfaceleadstotheformationofvegetations
(a) Vegetationsdevelopalongthelineofvalveclosure
(b) Vegetationsdeveloponthesideofbloodflow
(i) Atrialsideforatrioventricularvalves
(ii) Ventricularsideforsemilunarvalves

5) Themitralvalveisaffectedmostcommonly,followedbytheaorticvalve,thenthetricuspidvalve,
andfinallythepulmonicvalve
V) Endocarditis
A) Endocarditisisobservedunderfourmainconditions
1) Rheumaticheartdisease(RHDE)
2) Infectiousendocarditis(IE)
3) Nonbacterialthromboticendocarditis(NBTE)
4) LibmanSacksendocarditis(LSE)
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B) Infectiousendocarditis
1) Characteristics
(a) Bacterialvegetationsformingonthesurfacesofstructuralanomalies
(i) Ventricularseptaldefects
(ii) Atrialseptaldefects
(iii)
Patentductusarteriosus
(b) Vegetationsdeveloponthesideofbloodflow
(c) Thevegetationsmyextendintothesurroundingtissue,creatingdestructiveabscesses
(d) Leftsidedvalvesareaffectedmorecommonly
(i) RightsidedvalvesareaffectedinIVdrugusers
2) Etiologicagents
(a) Staphylococcusaureus
(b) Staphylococcusepidermidis
(c) Streptococcusviridans
(d) HACEKorganisms
(i) Haemophilus
(ii) Actinobacillus
(iii)
Cardiobacterium
(iv)Eikenella
(v) Kingella
(e) Fungal
(i) AspergillusandCandidaspecies
(f) Other
(i) EnterococcusandRickettsialorganisms
3) Clinicalpresentation
(a) Fever,malaise,andflulikesymptoms
(b) Evidenceofembolitomicrovasculature
(i) Petechiae
(ii) Subungalsplinterhemorrhages
(iii)
Rothspotsintheeyes
4) Histologicfindings
(a) Acute
(i) Combinationoffibrin,necroticdebris,organisms,andinflammatorycells(usually
neutrophils)
(b) Chronic
(i) Fibroustissue
(ii) Granulationtissue
5) Complications
(a) EndocarditisabscessvalvularinsufficiencyCHF
(b) Septicemboli
(c) Cardiacabscesses(ofteninthevalvering)
(d) Mycoticaneurysms
(e) Arrhythmia
C) Nonbacterialthrombotic(marantic)endocarditis
1) Characteristics
(a) Fibrinthrombiattachtovalvesurface
(b) Vegetationsdeveloponthesideofbloodflow
2) MorecommoninpatientspresentingwithhypercoaguablestatesorDIC
17

D) LibmanSacksendocarditis
1) ExclusivelyaffectspatientswithSLE
2) Sterilevegetationsdeveloponeithersideofthevalveorthechordaetendinae
3) Mayhealandscardeformationofthevalve
VI) ProstheticValves
A) Bioprostheticvalves
1) Typicallydonotrequireanticoagulation
2) Maybesourcedfromhumanorporcinetissues
3) Shorterlifespanthanmechanicalvalves
B) Mechanicalvalves
1) Requirelifelonganticoagulation
2) Longerlifespanthanbioprostheticvalves
PatternsofPulmonaryInjuryII
I) PulmonaryEmbolism
A) Mostpulmonaryemboliarisefromveinsinthelegs
1) Largeemboli(10%)cancausesaddleobstructionandcancausesuddendeath
2) Mediumemboli(20%)generallycauseinfarctions
3) Smallemboli(70%)havevariousfates
(a) Clinicallysilent
(b) Infarction
(c) Hemoptysis
B) Outcomes
1) Death
2) Mayresolvecompletelythroughthrombolysis
3) Mayleaveeccentricarterialscarsorwebs
4) Chronicthromboembolipulmonaryhypertension
II) PulmonaryHypertension
A) Medialhypertrophyofmuscularandelasticarteries
1) Increasesrightheartpressuresrightheartfailurecorpulmonaleanddeath
B) Types
1) Primary(idiopathic)
(a) MutationofBMPR2infamilialandsomesporadiccases
2) Secondary(mostcommon)
(a) COPD
(b) Chronicinterstitialpulmonarydisorders
(c) Chronicheartfailure
(d) Recurrentpulmonaryemboli
(e) Obstructivesleepapnea
(f) Drugs
C) Localizingthelesion

18

1) Pulmonaryarteries(pulmonaryembolism)
2) Pulmonarycapillaries(COPD,interstitialpulmonaryfibrosis,pulmonaryarterialhypertension)
3) Pulmonaryvenules(Anomalousvenoocclusivedisease)
4) Leftatrium(myxoma)
5) Leftventricle(DCM,HCM)
6) Aorta(hypertension)
III) PulmonaryVasculitis
A) Caninvolvearteries,veins,orcapillaries
B) Causes
1) Antineutrophilcytoplasmicantibodies(ANCA)
(a) WegenersvasculitisisanANCArelatedvasculitis
(i) Systemicinvolvement
o Upperrespiratorytract
o Kidneys
o Lungs
(ii) Threekeyfeatures
o Vasculitisinlargeandsmallvessels
o Necrosis(fibrinoidandregional)
o Granulomatousinflammation
2) Immunecomplexdiseases(e.g.,SLE)
3) Pulmonaryhemorrhage
4) Systemicdiseases
IV) PulmonaryInfections
A) Pneumonia
1) Alveolarpneumoniaismostcommon
(a) Involves(fills)alveoli
(b) Bacterialetiologies
(c) Types
(i) Lobarpneumoniaoccupiesanentirelobe
o Fourstages
Congestion(swellingofvessels)
Redhepatization(mildhemorrhage)
Grayhepatization(organization)
Resolution
19

B)

C)
D)
E)

F)

(ii) Bronchopneumoiainfiltratesthroughupperairway
2) Interstitialpneumonia
(a) Involvestissuebetweenalveoli
(b) Viralandatypicaletiologies
3) Pathogenesis
(a) Inhalationofinfectiousairdroplets
(b) Aspirationofinfectedsecretions/objects
(c) Hematogenousspread(secondarytobacteremia)
4) Predisposingfactors
(a) Decreasedcoughreflex
(b) Ciliarydysfunction/injury
(c) Decreasedfunctionofalveolarmacrophages
(d) Edema/congestion(e.g.,CHF)
(e) Retentionofsecretions
Abscess
1) Localizedsuppurativenecrosis
(a) Highlyvirulentorganismsareoftentheculprit(s)
2) Causes
(a) Aspiration
(b) Pneumonia
(c) Septicemboli
(d) Tumors
(e) Directinfection
Histoplasmosis
1) Associatedwithpigeonandbatdroppings
2) Calcifiedgranulomasareoftenfoundafterresolution
Blastomycosis
1) Associatedwithparticularsoils
Pulmonarytuberculosis
1) CausedbyMycobacteriumtuberculosis
2) Stagesoftuberculosis
(a) Primary
(i) Singlegranulomawithinparenchyma
(ii) Infectiontypicallydoesnotprogressresolutionviacalcification(Gohnnodule)
(iii)
MaydisseminatetomiliaryTB
(b) Secondary
(i) Reactivationorinfectionofsensitizedindividual
(ii) Cavitaryfibrocaseouslesions
(iii)
Bronchopneumonia
(iv)CandisseminatetomiliaryTB
Opportunisticpneumonias
1) Infectionsthataffectimmunosuppressedpatients
(a) AIDS
(b) Iatrogenic
(i) Cancerpatients
(ii) Transplantrecipients
2) Organisms
(a) Pneumocystis
20

(b) Aspergillus
(c) CMV
V) Pneumoconioses
A) General
1) Disorderscausedbyinhalationofinorganicelements(primarilymetals)
2) Injuryisdeterminedbyseveralfeatures
(a) Lengthofexposure
(b) Physicochemicalcharacteristics
(c) Hostfactors
B) Coalworkerspneumoconiosis(carbondust)
1) Anthracosis
2) Progressiontomassivefibrosis
C) Silicosis(silicon)
1) Smallnodulesinsideswirlinglesions
D) Asbestosis(asbestos)
1) Pulmonaryfibrosis
2) Pleuraldisease(e.g.,mesothelioma)
3) Lungcarcinomas
VI) Sarcoidosis
A) Systemicgranulomatousdisorderofunknownetiology
1) Majorityofcasesinvolvelungsandhilarlymphnodes
B) Pathology
1) Noncaseatinggranulomas
2) Pulmonaryfibrosisin~20%ofcases
VII) ChronicInterstitialLungDiseases
A) Idiopathicpulmonaryfibrosis(usualinterstitialpneumonia)
1) Progressivefibrosisofunknownetiology
2) Respiratoryandheartfailureensueswithinthreeyears
3) Honeycombappearancetolungswiththickwalls
(a) Activefibrosisisobservedattheboundarybetweenhealthyandscarredlung
(b) Strangely,theresnoinflammatorycellinfiltratethatdrivesthefibrosis
B) Nonspecificinterstitialpneumonia(NSIP)
1) Unknownetiologywithdiffuselymphocyticinfiltrate
C) Cryptogenicorganizingpneumonia(bronchitisobliteransorganizingpneumonia,BOOP)
1) Acuteillnessassociatedwithpriorrespiratoryinfection
2) Restrictivepatternoffibrosis
3) Responsivetosteroidtherapy
VIII) HypersensitivityPneumonitis
A) Immunemediateddisordersaffectingtheairwaysandinterstitium
B) Causedbyprolongedexposuretoinhaledantigens
C) Examples
1) Farmerslung
2) Pigeonbreederslung
3) Airconditionerlung
D) Characteristics
1) Bronchiolitis
2) Intersitiallymphocyteinvasion
3) Small,vaguegranulomas
21

E) Therapy
1) Avoidtrigger
2) Steroids
CongenitalHeartDisease
I) Overview
A) Statistics
1) CHDaffects0.251%oflivebirths
2) 10%ofcasesalsohaveachromosomalabnormality
(a) Themostcommonistrisomy21(Downsyndrome)
(b) Turnersyndrome(45,X)
(c) 22q11deletions(velocardiofacialsyndrome)
B) Verybroadphenotypicspectrum
C) Anatomydeterminesthephysiology,whichdeterminestheclinicalpresentation
1) Anatomy(andthusphysiologyandpresentation)maychangeovertime
II) ThreeMajorTypesofLesion
A) Lefttorightshunt
1) Features
(a) Oxygenatedbloodmixesintorightsidedcirculation
(b) Increasedbloodflowtopulmonaryarteries
2) Sequelae
(a) IncreasedpulmonarybloodflowpulmonaryhypertensionRVhypertrophyincreased
RVpressureshuntreversal(nowrighttoleft)cyanosis
(b) Eisenmengersyndromeisoftenthefinalresult
(i) Cyanosis
(ii) Exerciseintolerance
(iii)
Suddendeath
(c) Cyanosis
(i) Acrocyanosisiscyanosisofthehandsandfeet
o Canbenormalininfants
(ii) Perioralorcentralcyanosisiscyanosisofthelips,face,and/ortrunk
o Pathological
3) Examples
(a) Ventricularseptaldefect(VSD)
(b) Atrialseptaldefect(ASD)
(c) Patentductusarteriosus(PDA)
B) Righttoleftshunt
1) Features
(a) Deoxygenatedbloodmixesintosystemiccirculation
2) Sequelae
(a) Cyanoticheartdisease
(i) Failuretothrive
(ii) Polycythemia
(iii)
Clubbing
(iv)Cerebralhypoxia
3) Examples(theterribleTs)
(a) Transpositionofthegreatarteries
22

(b) TetralogyofFallot
(c) Truncusarteriosus
C) Obstruction
1) Features
(a) Completeorpartialblockageofanoutflowtract
(b) Frequentlyassociatedwithashunt
(i) Inorderforsomeobstructionstobecompatiblewithlife,ashuntmustbepresent
(ii) Inthesecases,itsimperativethatprostaglandinEadministrationorsurgicalintervention
takeplaceinordertopreservetheshunt
2) Examples
(a) Aorticcoarctation
(b) Aorticstenosis/atresia
(c) Pulmonarystenosis
D) Combinedlesions
1) Exhibitfeaturesfrommultiplecategories
III) DuctusArteriosus
A) Anatomy
1) Actsasaconduitbetweenthebifurcationofthepulmonaryarteryandthetransverseaorticarch
2) Inthefetus,theductusarteriosuscarriesoxygenatedbloodfromtherightheartintothesystemic
circulation,bypassingthelungs
(a) Recallthattherightheartisoxygenatedinthefetusbecausebloodisreturningfromtheplacenta,
wherefetalgasexchangeoccurs
B) Closureisstimulatedbydecreasingprostaglandinlevelswithin24hoursafterbirth
1) NSAIDSinhibitprostaglandinsynthesisandcanstimulateclosure
2) ProstaglandinEinfusioncankeeptheductusarteriosusopen
C) PDAisassociatedwithcongenitalrubella
IV) VentricularSeptalDefect
A) Features
1) Lefttorightshunting
2) Twomajortypes
(a) Membranous(85%)
(i) Mostcommonlocationisjustbelowtheaorticvalve
(b) Infundibularormuscular(15%)
(i) Mayclosespontaneously
B) Presentationvarieswiththesizeofthehole
1) LargeVSDswillpresentatbirthwithsymptomsofheartfailure
2) SmallVSDswillpresentlaterwithamurmurorEisenmengersyndrome
C) Associatedwithfetalalcoholsyndrome
V) AtrialSeptalDefect
A) Features
1) Lefttorightshunting
2) Threemajortypes
(a) Secundum(90%,A)
(i) Defectinforamenovale
(b) Primum(5%,B)
(i) Defectinatrialwall(typicallybetweenAVvalves)
(c) Sinusvenosusdefect(5%,C)
23

B) Presentation
1) Flowmurmurduetotheexcessflowthroughthepulmonicvalve
2) Maybeasymptomaticinadults
C) AssociatedwithDownSyndrome(trisomy21)
VI) AtrioventricularCanal
A) Features
1) Endocardialcushiondefectthatinvolvesincompleteformationofthreecomponents
(a) LoweratrialseptumASD
(b) MembranousventricularseptumVSD
(c) AtrioventricularvalvesAVcanal
(i) Instead,thereisasingle,common,5leafletvalvethatencirclesthecenteroftheheart
B) Presentation
1) 50%ofcasesareassociatedwithtrisomy21(Downsyndrome)
2) Conversely,50%oftrisomy21casesareassociatedwithsomecongenitalheartdefect
VII) TranspositionoftheGreatArteries
A) Features
1) Therightventricleisconnectedtotheaorta
2) Theleftventricleisconnectedtothepulmonaryartery
3) Requiresashunttoremainviable
(a) VSD(40%)
(b) PFOorPDA(60%)
(i) Theseareunstableandrequireanatrialseptostomy(surgicalcreationofanASD)inthefirst
daysoflife
B) Presentation
1) Cyanoticheartdisease
2) Associationwith22q11deletion
(a) Autosomaldominantmutationwithvariablepenetrance
(b) 3MBdeletionthatmaybedetectedbykaryotypeorFISH
(c) Includesathymichypoplasia/aplasiaSCID
3) Alsoassociatedwithmaternaldiabetes
C) Surgicallycorrectedbyswitchingthearteriesandreimplantingthecoronaryarteries
VIII) TruncusArteriosus
A) Features
1) Theaortaandpulmonaryarteryshareacommonoutflowtractoverridingasingletruncalvalve
24

2) RequiresanunderlyingVSDforsurvival
B) Presentation
1) Manyhaveotheraorticarchorcoronaryarteryanomalies
2) Earlydevelopmentofcyanosis
3) Latecyanoticheartdisease
4) Increasedpulmonarybloodflow
5) Associationwith22q11deletion
IX) TetralogyofFallot
A) Mostcommoncongenitalheartdefect
B) Features(mustknowthese)
1) Pulmonaryoutflowtractstenosis
2) Overridingaorta
3) VSD
4) RVhypertrophy
C) Presentationcandependonthedegreeofrightventricularoutflowtractobstruction
1) Cyanoticepisodes(tetspells)duetospasmoftherightventricularoutflowtract
2) MildobstructionhassymptomssimilartoanisolatedVSD(e.g.,murmurandEisenmenger)
3) Severeobstructionwillproducearighttoleftshuntandcyanoticheartdisease
X) AorticCoarctation
A) Features
1) Abruptnarrowingattheleveloftheductusarteriosus
B) Presentation
1) Heartfailureininfancy
2) Variablebloodpressurebetweentheupperandlowerextremities
C) Associations
1) Othercongenitalmalformation
(a) Bicuspidaorticvalve(4050%)
(b) VSD(4050%)
(c) Otherlesions(25%)
2) Turnersyndrome(45,X)
Acyanotic
VSD(fetalalcoholsyndrome)
ASD(trisomy21)
PDA(congenitalrubella)
AVcanal(trisomy21)

SummaryofCongenitalHeartDefects
Cyanotic
Transposition(diabetes,22q11.2)
TetralogyofFallot(22q11.2)
Truncusarteriosus(22q11.2)
Tricuspidatresia
Coarctationoftheaorta(Turnersyndrome,bicuspidaorticvalve)

HypertensionandVascularDiseases
I) SystemicHypertension
A) Introduction
1) DefinedasconsistentBP>140/90mmHg
2) Predisposesindividualstoatherosclerosis(leadingtocoronaryheartdisease,peripheralvascular
disease,andstroke),congestiveheartfailure,andrenalfailure
3) Servesasasilentkillerthatdamagesallorgans
(a) Maypresentwithstroke,heartattack,aneurysmrupture,etc.
25

4) BPvarieswiththecircadianrhythm,whichmustbeaccountedforwhentakingBPmeasurementsfor
thesakeofdiagnosis
B) BPresultsfromthecombinedeffectsofcardiacoutputandvascularresistance(setprimarilybythe
arterioles)
1) COdependslargelyonbloodvolume,whichdependsonsodiumhomeostasis
2) Thekidneythusplaysanimportantroleinbloodpressureviatherenin/angiotensinsystem
C) Classifications
1) Primary(essential)hypertension
(a) Idiopathiccause(maybefamilial)
(b) Onsettypicallyoccursafterage40
(c) Usuallyrespondswelltotreatment
(d) Represents95%ofallhypertensioncases
2) Malignant(accelerated)hypertension
(a) Aprogressionofbenignhypertensionthatbecomesrapidlysymptomatic
(i) BP>200/120mmHg
(b) Symptoms
(i) Headache
(ii) Blurredvisionandretinopathy
(iii)
Encephalopathy
(iv)LVhypertrophy
(v) Hyperplasticarteriosclerosis
o Fibrinoidnecrosisandintimalhyperplasiainsmallarterioles
o Thiscanbesoseverethatthelumenisobliterated
3) Secondaryhypertension
(a) Onlyrepresents5%ofcases,butisaveryimportantdiagnosis
(b) Treatingtheunderlyingpathologywilltypicallycurethehypertension
(c) Causes
(i) Renal
(ii) Endocrine
(iii)
Cardiovascular
(iv)Neurological
(v) Druginduced

26

II) MorphologyofHypertension
A) Hypertensivevascularchangesareusuallyfoundinsmallarteriesandarterioles
1) Hyalinearteriosclerosis(associatedwithbenignhypertension)
(a) Accumulationofahomogenous,eosinophilicmaterialthickensthevesselwallandnarrowsthe
lumen
(b) Causedbyleakageofplasmaconstituentsacrossthevascularendothelium,leadingtoendothelial
damage,invasionofmyointimalcells,anddepositionofmatrixproteins(hyaline)
2) Hyperplasticarteriosclerosis(associatedwithmalignanthypertension)
(a) Fibrinoidnecrosisofthevascularwall
(b) Intimalhyperplasia
(c) Maybesoseverethatthelumenisactuallyobliterated/occluded
B) Effectsontheheart
1) Concentricleftventricularhypertrophy(pressureoverload)
2) LVHdiastolicdysfunctionleftatrialenlargement
3) Heartfailure
4) Treatmentwillreversemuchofthehypertrophy
C) Effectsonthekidneys
27

1) Hyalinearteriosclerosisinresponsetobenignhypertension
2) Hyperplasticarteriosclerosisinresponsetomalignanthypertension
D) Effectsonthebrain
1) Infarctionduetoatherosclerosisandthrombosis
2) Cerebralhemorrhage
E) Effectsonthelungs
1) AcuteedemainresponsetoLVfailure
2) Infarction
3) Terminalbronchopneumonia
III) Aneurysms
A) Introduction
1) Definedasalocalized,abnormaldilationofabloodvessel(usuallyanartery)
2) Twopossiblemechanismsofformation
(a) Weakeningofthevesselwall
(b) Overdistentionofthevessel
B) Classifications
1) Trueaneurysms
(a) Haveremnantsoftheoriginalarterywall
2) Falseaneurysms(pseudoaneurysms)
(a) Breachinthevesselwallpulsatinghematoma
C) Aneurysmmorphology
1) Fusiform(cylindrical)
(a) Aneurysmisduetoatherosclerosis
(b) Theentirearterialcircumferenceisdilated
(c) Mostcommonaneurysmintheelderly
(d) Abdominalaorticaneurysms(AAA)belowtherenalarteriesaremostcommon
(e) Mayhavefamilialpredispositioninmales
2) Saccular
(a) Resultsfromweakeningofasmallportionofthearterywall
(b) Asmallostiumconnectstheaneurysmtotheartery
(c) Causes/examples
(i) Syphiliticaortits(complicationoftertiarysyphiliswhichoccludesvasavasorum)
(ii) BerryaneurysmofthecircleofWillis(focaldefectinarterialmediathatmaybeassociated
withsomeinheriteddiseases)
(iii)
Arteritis
(iv)Mycoticaneurysm(causedbyinfection)
3) Dissecting(acuteaorticdissection)
(a) Anintramuralhematomawithinanarterialwallcreatesafalsechannelwithinthemedia
(i) Occursbetweentheinner2/3andouter1/3ofthetunicamedia
(b) Causes
(i) Medionecrosis
o CysticmedialnecrosismaybeassociatedwithMarfansSyndrome
(ii) Hypertension
(iii)
Pregnancy(veryrarely)
(c) Complications
(i) Ruptureintoadjacentcavity(pericardial,pleural,orperitoneal)
(ii) Vascularobstruction(causedbyextensionofthedissectionintobranchingarteries)
(iii)
Aorticinsufficiency(duetoretrogradedissectionoftheaorticroot)
28

4) Microaneurysms
(a) Aneurysmsofsmallvessels,typically<300mindiameter
(b) Causes
(i) Diabetesmellitus(affectsretinaandheart)
(ii) Thromboticpurpura
(iii)
CharcotBouchardaneurysms(tinyaneurysmsinthebasalgangliasecondaryto
hypertension)

D) Cardiacaneurysms
1) Usuallyresultfromamyocardialinfarction
2) Truecardiacaneurysm
(a) Resultfromahealedtransmuralinfarct
(b) Virtuallyneverruptures
(c) Mayleadtoarrhythmiaorheartfailure
3) Falsecardiacaneurysm(veryrare)
(a) Infarctedmyocardiumruptures,butadherentpericardiumdoesnot
(i) Thustheaneurysmwallconsistsofintactpericardium
(b) Verypronetorupture
IV) Vasculitis
A) Introduction
1) Destructiveinflammationofbloodvessels
2) Mayaffectarteries,veins,and/orcapillaries
3) Potentialsequelae
(a) Vascularthrombosis
(b) Aneurysm
(c) Acutevesselocclusionbyaninsituclot
B) Etiologies
1) Bothinfectiousandnoninfectioustypes
2) Immunecomplexmediated(HepatitisB,SLE)
3) Antineutrophilcytoplasmicantibody(ANCA)mediated(Wegenersgranulomatosis)
4) Directantibodymediated(Kawasakisdisease)
5) Cellmediated(organ/allograftrejection)
6) Unknown(giantcellarteritis)
C) Giantcellarteritis(temporalarteritis)
1) Mostcommonformofvasculitisintheelderly(>50yearsofage)
2) Involvesmedium/largearteriesinthehead
(a) Granulomatousinflammationwithfocaldestructionofinternalelasticlamina
3) Clinicalfindings
(a) Abnormallytendertemporalartery
(b) ESRelevation
(c) Headache,fever,fatigue
29

4) EtiologymaybeTcellmediated
D) Polyarteritisnodosa
1) Systemicvasculitisofsmall/mediummusculararteries
2) Immunecomplexdisease(somepatientshavecirculatingHepatitisBcomplexes)
3) Affectsnumerousorgans
4) Fibrinoidnecrosisofthevesselwasisobserved
E) Kawasakidisease
1) Inflammationofmedium/largearteries
2) Mostcommoncauseofacquiredheartdiseaseinchildren
3) Delayedtypehypersensitivityreactionagainstanunknownantigenproductionofantiendothelial
cellantibodies
ANGITIS

VESSELS
INVOLVED

ORGANORTISSUE
AFFECTED

PRINCIPALMORPHOLOGICFEATURES

Polyarteritis
nodosa

Muscular
arteries

Gastrointestinaltract,mesentery,
liver,gallbladder,kidney,
pancreas,muscles,othersites

Lesionsofvaryingages:alllayersofvesselswith
acutefibrinoidnecrosisandextensiveperiarterial
inflammation

Hypersensitivity
angitis

Smallvenules
capillaries,
arterioles

Allorgansandtissues(skin,
muscles,heart,kidneys,lungs)

Acutenecrotizingvasculitiswithfibrinoidnecrosisof
entirewall:oftenthrombosisoflumen

Giantcellarteritis
(temporal
arteritis)

Muscular
arteries

Usuallytemporal,ophthalmic,
andcranialarteries:maybe
systemic

Disruptionofelasticlaminawithmostintense
reactioninintimalmediallayers:giantcellsengulf
elasticfiberfragments:occasionallythrombosisof
lumen

Takayasus
arteritis

Aorta,arteries

Extremities:headandneck;
viscera

Granulomatousarteritiswithfibrosisandmarked
narrowingpatientslessthan50yearsofage

Kawasakis
Disease

Arteries

Generalized:coronaryarteries

Identicaltopolyarteritis(infantilepolyarteritis);
Aneurysms

Wegeners
granulomatosis

Smallarteries
andveins

Lung,kidneys,upperrespiratory
tract:
occasionallysystemic

Acutenecrotizingvasculitiswithfibrinoidnecrosisof
vesselwall:oftenproximatetogranulomasintissues

30