HD1Respiratory

PulmonaryFunctionTests
I) BreathingMechanics
A) Normalmechanics
1) Inspiration
(a) Contractionofthediaphragmreducesthepleuralpressure
(b) Alveoliexpandasairisdrawnin
(c) Flowisresistedbytheradiusoftheairwayandtheelasticrecoilofthealveoli
(i) Asthelungexpands,however,airwayswidenandresistancedecreasesproportionallyto1/r4
2) Forcedexpiration
(a) Relaxationofthediaphragm,contractionofabdominalmuscles,andalveolarelasticrecoilwork
toexpelairfromthealveoli
(b) Asthelungempties,thepleuralpressureincreasesandbeginscollapsingtheairways
(c) Astheairwayscollapse,resistanceincreasesanddecreasesflowproportionally(1/r4)
(d) Eventually,astateofeffortindependentexpirationisreached,whereadditionaleffortfailsto
increaseexpiratoryflow
B) Obstructivemechanics
1) Obstructiveairwayshavetwoessentialproblems
(a) Lossofalveolarelasticrecoil
(b) Lossoftetheringthatnormallysupportsopenairways
2) Ultimately,thedynamiccompressionofairwaysinexpirationisaccentuated,andexpiratoryflowis
greatlyreduced
II) Spirometry
A) Features
1) Measuresbothvolumeandflowrateasgasenters/exitsthelungs
2) Answerstwoimportantquestions
(a) Howbigarethelungs?
(b) Howwelldotheyempty?
3) Permitsdifferentiationbetweenobstructiveandrestrictivedisease
B) Staticlungvolumes

Spirometry

Static Lung Volumes

1) Definitions
TV = VT = tidal volume = vol. of gas inhaled or exhaled during each
(a) Tidalvolume(TV)representsthevolumeofgasinhaledandexhaledduringanormal,resting
respiratory cycle
respiratorycycle
IRV (inspiratory reserve vol.) and ERV (expiratory reserve vol.) =
(b) Inspiratoryreservevolume(IRV)representstheadditionalvolumeofairthatcouldbeforcibly
the additional volume of gas that can be forcibly inhaled or exhaled
inhaledbeyondthetidalvolume
beyond the resting VT

(c) Expiratoryreservevolume(ERV)representstheadditionalvolumeofairthatcouldbeforcibly
exhaledbeyondthetidalvolume
(d) Vitalcapacity(VC)representsthemaximumvolumeofgasthatcanbeexhaledfromthetotal
lungcapacity
(i) Thevitalcapacityisthevolumedirectlyassessedinspirometry
(e) Residualvolume(RV)representsthevolumeofairthatremainsinthelungsfollowingmaximal
expiration
(f) Totallungcapacity(TLC)representsthecompleteandtotalvolumeofthelungs
C) Normalspirometry
1) Theforcedexpiratoryvolumein1second(FEV1)representstheamountofairforciblyexhaledin
onesecond
(a) Normalis>80%ofthepredictedvalue
2) Theforcedvitalcapacity(FVC)representsthemaximumamountofairforciblyexhaledfollowing
maximuminhalation
(a) Normalis>80%ofthepredictedvalue
3) TheratioofFEV1/FVCisclinicallyimportantindistinguishingobstructiveandrestrictivedisease
(a) Minimalvalueisindividualizedbasedonthepatientsage,heightandrace
(b) Traditionally,normalvaluesare>70%
D) Obstructivespirometry
1) DecreasedFEV1/FVCdefinesthepresenceofanobstruction
2) TheFEV1determinestheseverityoftheobstruction
E) Restrictivespirometry
1) TheFEV1/FVCisoftennormalorelevatedinrestrictivedisease
2) TheFVCislowered
3) TLCisusedtodetermineseverity
III) FlowVolumeLoops
A) Featuresandnormalflowvolumeloop
Normal Flow-volume Loop
1) Variationofspirometrythatplotsflow(L/min)againstvolume(L)
2) Differentiateslowerairwaydisease(e.g.asthma)fromupperairwayobstruction
Expiratory
limb
Flow in
liters/min

RV

TLC
Inspiratory
limb
Volume in L

B) Obstructiveflowvolumeloop
1) Slowemptyingfromthenarrowairwaysshowsupasadipintheexpiratorylimb
C) Restrictiveflowvolumeloop
1) Highflowratescanbeobtained,butthelowervolumesnarrowtheloop
D) Variableextrathoracicupperairwayobstruction
1) Inhalationgeneratesnegativepressureinthelarge,upperairways
2) Ifanextrathoracicobstructionispresent,thenegativepressurefrominhalationwillaccentuatethe
obstruction
(a) Obstructionsincludetumor,stenosis,etc.
2

3) Aflattenedinspiratorylimbisobserved
E) Variableintrathoracicupperairwayobstruction
1) Exhalationcompressesthelungsand,inturn,theupperairways
2) Ifanintrathoracicobstructionispresent,thecompressionfromexhalationwillaccentuatethe
obstruction
3) Aflattenedexpiratorylimbisobserved
F) Fixedupperairwayobstruction
1) Bothinspiratoryandexpiratorylimbsareflattened

IV) LungVolumes
A) Gasdilution
1) Inhalationofaknownvolumeofheliumandcalculatingtheresultingdilutedconcentrationpermits
measurementoffunctionalresidualcapacity(FRC)
2) Mayunderestimatelungvolumeifareasoflungcommunicatepoorlywiththebronchialtree(asin
bullousemphysema)
B) Bodyplethysmography
1) Apatientbreathsintoaboxandagainstaclosedshutter
2) BoylesLawisusedtocorrelatepressureandvolumechangestothepatientsFRC
3) Goldstandardforlungvolumedetermination
C) Diffusingcapacityofthelungforcarbonmonoxide(DLCO)
1) MeasurestheabilityofinhaledCOtocrossthealveolar/capillarywallandbindhemoglobin
(a) Comparesinhaled[CO]toexhaled[CO]
2) Determinantsofdiffusingcapacity
(a) Alveolar/capillarysurfacearea
(b) Volumeofbloodandhemoglobin
(c) Alveolarmembranethicknessislessimportant
3) Differentiatesdestructivelungdiseases(e.g.COPDfromasthma)
4) InterpretationofDLCO

V) Integration

ChronicObstructivePulmonaryDisease(COPD)
I) PrevalenceofCOPD
A) COPDisabigdeal
1) 21millioncasesannualy
2) Projectedtoincreaseinprevalence
3) Affectsmenandwomen
(a) Womenaremoresusceptibleandhavemorecomorbidities
II) PathophysiologyofCOPD
A) Riskfactors
1) Smoking
(a) ImportanttorememberthatnoteveryonewhosmokeswillgetCOPD
(b) However,themajorityofCOPDcasesaredirectlylinkedtosmoking
2) Protease/antiproteaseimbalance
(a) 1antitrypsindeficiency
(i) Canbetreatedwithadministrationofrecombinant1antitrypsin
3) Infection
(a) Previouscaseoftuberculosis,especially
4) Geneticfactors
5) Air/environmentalpollution
6) Lunggrowthanddevelopmentabnormalities
7) Age
4

8) Gender
9) Socioeconomicstatus
10) Bronchialhyperreactivity
B) Canbeconsideredanoverlapofobstructivebronchiolitisandemphysema
1) Obstructivebronchiolitisisasmallairwaydiseasewithtwomajoretiologies
(a) Inflammation
(b) Remodeling
2) Emphysemaisananatomicdiagnosis
(a) Dilationanddestructionofairspacesdistaltotheterminalbronchiole
(b) Lossofsupportiveelastictissue
3) Results
(a) Poorlyreversibleairflowlimitation
(i) Smoothmusclecontraction
(ii) Bronchoconstriction
(iii)
Mucushypersecretion
(iv)Lossofelasticrecoil
(v) Increasedcholinergictone
(vi)Airwaynarrowing
(b) Progressivedestructionofstructuralelements
(i) Alveolardestruction
(ii) Collagendeposition
(iii)
Glandularhypertrophy
(iv)Airwayfibrosis
(c) Abnormalinflammatoryresponseofthelung
(i) Increasedoxidativestress
(ii) Increasedleukocyteactivity
(iii)
Protease/antiproteaseimbalance
C) Clinicalfeatures
1) Dyspnea
(a) Exertional(dynamichyperinflation)
(b) Nocturnal(circadianrhythm)
2) Cough
(a) Productiveornonproductive
3) Exacerbations
(a) Seriousclinicalillnesses
4) Hyperinflatedchest
5) Wheezingordecreasedbreathsounds
6) Prolongedexpiratoryphase
7) Useofaccessorymusclesofrespiration
8) Peripheraledemaandenlargedheart(CHF)
9) Hypoxemiacyanosis
(a) DuetoV/Qmismatch,increasingshunteffect
10) Hypercarbia
(a) DuetoV/Qmismatch,increasingdeadspace
D) Diagnosis
1) Spirometry
(a) DecreasedFEV1/FVC
III) ManagementofCOPD
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A) Reduceriskfactors
1) Smokingcessation
2) InfluenzaandPneumococcalvaccination
B) Pulmonaryrehabilitation
C) Bronchodilators
1) 2agonists(albuterol)
2) Anticholinergics(ipratropium)
D) Inhaledcorticosteroids
1) Mayalsotryotherpharmacologictreatmentsatthisstage
(a) 1antitrypsintherapy
(b) Antioxidants
(c) Phosphodiesterase4inhibitors
(i) ShowpromiseinreducingsevereexacerbationsandimprovingFEV1
E) Palliativecare
F) Oxygen
1) Commonlypracticed,thoughtheactualbenefitmaybeoverestimated
G) Surgery
1) Lungtransplant
2) Lungvolumereductionsurgery(LVRS)
(a) Byremoving(eitherfunctionallyoranatomically)thecompromisedportionofthelung,the
healthylungisabletoexpandintothenewlycreatedvoid,effectivelyincreasingTLC
ChestImaging
I) ChestXRays(CXRs)
A) Basicimagingconcepts
1) Silhouettesign
(a) Bordersaregeneratedattheinterfacebetweentwomaterialswithdifferentdensities(andthus
differentopacitiestoXrays)
2) Summationofshadows
(a) WhenmultiplematerialsareinlinewithabeamofXrays,eachindividualmaterialwillstill
absorbquantaofXraysappropriateforitsdensity
(b) Thus,thetotalabsorbanceofXraysinthatlinewillbethesummationoftheindividuals
absorbenciesofeachmaterial
3) Scatterandmagnificationwithdistance
(a) Thefartherananatomicalstructureisfromthefilm(andcloseritistotheradiationsource),the
morediffuseandmagnifieditwillappearintheCXR
B) ViewsusedforCXRs
1) Posteroanterior(PA)
(a) Xrayspassthroughthepatientfrombacktofront
2) Lateralview
(a) Leftsideisplacedagainstthefilmcassette
(i) Thus,rightsidedstructuresaremagnified
3) Anteroposterior(AP)
(a) Xrayspassthroughthepatientfromfronttoback
(b) OftenobtainedfromportableXraydevicesinbedriddenpatients
(c) Technicalproblems
(i) Cardiacmagnification
6

(ii) Patientisnotupright
(iii)
Skinfoldsmaybevisible
4) Lateraldecubitus
(a) Patientislayingontheirside
(b) Demonstratesshiftingfluidsandpneumothorax
5) Apicallordoticview
(a) PAfilmwithXraysangledcranially
(b) Helpsvisualizeapical/upperlobes
(c) Movesclaviclesupwardsandoutoftheway
6) Obliqueviews(LAO,RAO)
(a) Rarelyusedtovisualizeabnormalities
C) Normalanatomyofthechest
1) Lobesandfissures
2) Trachea
3) Heart

4) Hilum

5) Mediastinum

6) Bone
7) Blindspots

D) Basicpulmonarypathology
1) Atelectasis(volumelossduetoalveolarcollapse)
2) Pleuraleffusions(fluidoccupiespleuralspace)
(a) Canappearaspseudotumorsintheinterlobarfissures
3) Pneumothorax(airoccupiespleuralspace)
4) Pneumonia(bacterialinfections)
5) Pulmonarynodules
(a) Coinlesions(accidentalinhalationofsparechange)
(b) Neoplasms
6) COPD(hyperinflatedlungfields)
II) ComputedTomography(CT)
A) Basicimagingconcepts
1) SpiralCTmethodologyallowsrapidscanningoftheentirechest(~20seconds)
8

2) ResolutionandcontrastaresuperiortoCXR,makingCTmoreappropriateforearlydetectionof
neoplasms
(a) Detectionofmicrocalcificationsisanotheradvantage/indication

Asthma
I) IntroductionandEpidemiology
A) Asthmaisachronicinflammatorydisorderoftheairways
B) Oneofthemostcommonchronicdiseases
1) Estimated300millionaffectedindividuals
2) Healthcareexpendituresarehigh
3) Morecommoninsomepopulations
(a) Children(<5yearsold)
(b) Women
(c) Blacks
C) Typesofasthma
1) Intrinsic(nonatopic)
2) Extrinsic(atopic)
(a) Majorform
(b) Mediatedbyinflammatorymechanisms
3) Exercisedinduced
(a) Trueexercisedinducedbronchoconstrictionisrare
4) Aspirinsensitive
(a) Associatedwithnasalpolyps
5) Occupational
D) Riskfactors
1) Hostfactors
(a) Geneticpredisposition
(i) Atopy
(ii) Airwayhyperresponsiveness
(b) Gender
(c) Obesity
2) Environmentalfactors
9

(a) Indoor/outdoorallergens
(b) Occupationalsensitizers
(c) Tobaccosmoke
(d) Airpollution
(e) Respiratoryinfections
(f) Diet
E) Triggers
1) Allergens
2) Respiratoryinfections
3) Exerciseandhyperventilation
4) Weatherchanges
5) Sulfurdioxide
6) Food,additives,drugs
7) Acidreflux
8) Sleepapnea
9) Stress
II) Pathophysiology
A) Briefprocess
1) AninhaledallergenactivatesmastcellsbycrosslinkingIgEontheirsurface
2) Mascellsreleasehistamine,leukotrienes,andPGD2,leadingtobronchoconstriction
B) Mediatorsthatarehighlyimplicatedinthisproinflammatoryprocess
1) TH2cells
2) Eosinophils
3) IL2,4,5,and10
C) Pathology
1) Smoothmuscleconstrictionhypertrophyandhyperplasiaofbronchialsmoothmuscle
2) Eosinophilandlymphocyteinvasionairwaywalledema
3) Hyperplasiaofgobletcellsincreasedmucousproduction
4) Airwayremodelingandscarring,includingthickeningofthebasementmembrane
D) Physiology
1) Airflowobstruction
(a) DecreasedFEV1,FEV1/FVC,andPEF
2) Hyperinflation
(a) IncreasedTLC
3) Gastrapping
(a) IncreasedRV,FRC,andRV/TLC
4) Normalalveolar/capillarydiffusion(DLCO)
5) Spirometrymaybenormalinmildcases

10

6) Gasexchange
(a) DecreasedPaO2
(b) IncreasedPaCO2
(c) V/Qmismatchcanbecorrectedwithapplicationofoxygen,butshuntingcannot
III) Diagnosis
A) Diagnosisisbasedonseveralkeyfactors
1) History
2) Spirometry
(a) FEV1
(b) Peakexpiratoryflowrate
3) Measurementofairwayresponsiveness
(a) Methacholinechallengetest
(b) Exercisechallengetest
4) Measurementofallergicstatus(IgEtitersandCBC)
B) Differential
1) COPD
2) Cysticfibrosis(especiallyimportanttotestforinchildrenwithnasalpolyps)
3) Bronchiectasis
4) CHF
5) Paroxysmalvocalcorddysfunction
6) Acidreflux
7) Otherobstructions(tumor,foreignbody,bronchiolitis,etc.)
IV) TreatmentandManagement
A) Goalsoflongtermmanagement
1) Controlsymptoms
2) Maintainnormalactivitylevels(includingexercise)
3) Maintainnormalpulmonaryfunction
4) Preventexacerbations
5) Avoidadversemedicationeffects
6) Preventmortality
B) Controllingmedications
1) Inhaledglucocorticoids
(a) Thesearethemosteffective,andthusthemostwidelyused
2) Leukotrienemodifiers
(a) Moreconvenient(pill),butnotaseffective
3) Longlastinginhaled2agonists
11

C)

D)

E)
F)

4) Longlastinganticholinergics
5) Theophylline
6) Cromones
7) Longactingoral2agonists
8) AntiIgEtherapy
9) Systemicglucocorticosteroids
Relievingmedications
1) Rapidactinginhaled2agonists
2) Systemicglucocorticosteroids
3) Anticholinergics
4) Theophylline
5) Shortactingoral2agonists
Newtreatments
1) Bronchialthermoplasty
2) Tiotropium(longactinganticholinergic)
3) Intermittentcorticosteroidtherapy
Treatingchildren(<5yearsold)
1) Childrenmaymetabolizemedicationsmorerapidly
Treatinganemergentexacerbation
1) Repetitiveadministrationofrapidactinginhaled2agonists
2) Introductionofsystemicglucocorticosteroids
3) Oxygensupplementation
AcuteRespiratoryFailure

I) Introduction
A) Signsandsymptomsofpoorgasexchange(manyarenonspecific)
1) Hypercapniaheadacheordecreasedlevelofconsciousness
2) Vasodilationflushingand/orsweating
3) Hypoxemiaseveraleffects
(a) Confusion,restlessness,impairedjudgement,paranoia
(b) Sympatheticresponsehypertensionand/ortachycardia
(c) Cyanosis
4) Dyspnea(moreusefulwheninaclinicalsettingwhererespiratoryfailureislikelytooccur)
B) Detectionandapproach
1) Oximetryisthefirstapproach
2) Arterialbloodgastestingcanbeusedliberally
II) ArterialBloodGasses(ABGs)
A) PaCO2asameasureofalveolarventilation
1) Normally,PaCO2ismaintainedat40mmHgbythecentralrespiratorycenter
2) CO2ispoorlysolubleinaqueoussolutions,andisthustransportedascarbonicacidintheblood
(a) Thistransportsystemisnotsaturable,whichisthekeydistinguisherfromO2transport
B) Acid/BaseStatus
1) Respiratoryacidosis
(a) AlveolarhypoventilationincreasesPaCO2increasedcarbonicaciddecreasedpH
(b) Inacuterespiratoryacidosis,thepHfalls0.08unitsforeach10mmHgincreaseinPaCO2
(c) Inchronicrespiratoryacidosis,thepHfalls0.03unitsper10mmHgincreaseinPaCO2
12

(i) Thegradualincreaseinbicarbonatebetweentheacuteandchronicphasesisduetorenal
compensation
2) Respiratoryalkalosis
(a) AlveolarhyperventilationdecreasesPaCO2decreasedcarbonicacidincreasedpH
(b) Inacuterespiratoryalkalosis,thepHincreases0.08unitsper10mmHgdecreaseinPaCO2
(c) Inchronicrespiratoryalkalosis,thepHincreases0.02unitsper10mmHgdecreaseinPaCO2
(i) Thegradualdecreaseinbicarbonatebetweentheacuteandchronicrespiratoryphasesisdue
torenalcompensation
C) PaO2asameasureofbloodoxygenation
1) Normalarterialbloodgases
(a) PaO2=100mmHg
(b) PaCO2=40mmHg
(c) pH=7.40
(d) HCO3=25mEq/L
2) CorrelationbetweenPaO2valuesandO2saturation
(a) Sigmoidalfunction,duetocooperativityofhemoglobin
(b)
RelationshipbetweenPaO2andO2Saturation
PaO2(mmHg)
100
90
60
50
40
28

O2Saturation
99%
95%
90%
85%
75%
50%

D) EfficiencyofgasexchangeandtheAagradient
1) Thealveolararterial(Aa)gradientdescribesthedifferencebetweenalveolarandarterialoxygen
(a) Inbellowsfailure,theAagradientremainsnormal(thehypoxemiaisdueonlytoinadequate
ventilationofthelungs)
(b) InV/Qmismatchingandshunting,theAagradientispathologicallyincreased(>15mmHg)
2) CalculationoftheAagradientrequiresknowledgeofseveralvalues
(a) Fractionofinspiredoxygen
(b) PaCO2(obtainedfromABGtesting)
(c) PaO2(obtainedfromABGtesting)
3) Calculatinghealveolar/arterialdifference
(a) P Alv P Art =( Alv Art ) P O
(b) Ideally,therewouldbenodifferencebetweenarterialandalveolarPO2becausediffusionwould
equilibratethetwointhepulmonarycapillarybeds
(i) Physiologicvalues,however,deviatefromtheideal
o Healthy:510mmHgdifferential
o Pathologic:>15mmHgdifferential
(c) Calculatingthe(AlvArt)PO2
(i) Mostoften,arterialPO2canbedeterminedfromarterialbloodgastesting
(ii) AlveolarPO2mustbeestimatedusingacombinedderivationoftwootherequations
o IftheempiricalequationsforarterialPO2andPCO2(seeabove)arejoinedbysolvingthe
PCO2equationforVAandsubstitutingitintothePO2equation,theresultingformulais:
P Alv

P Alv =P I
R
O2

O2

CO2

O2

O2

13

WhereRistherespiratoryquotient,and R=

V CO
=0.8
VO
2

ThissignifiesthatthevolumeofCO2thatweexhaleistypically80%ofthe
volumeofO2thatweinhale
However,wedontknowthealveolarPCO2
Fortunately,thealveolarPCO2isvirtuallyidenticaltothearterialPCO2,whichisalso
measuredwitharterialbloodgastesting
Therefore,the(AlvArt)PO2canbedetermineddirectlyfrombloodgastestingviathe
followingequation:
P Art

( Alv Art ) P O =P Alv P Art = PI

P Art
R
Recallthat
PI =( PBarometric P H O ) F I =( 747 mmHg47 mmHg ) 0.21=150 mmHg
IftheFIO2increases,sowillthePIO2andsubsequentlytheAagradient
Thiscanbeexploitedclinicallybyadministeringconcentratedoxygentoahypoxic
patient

o
o
o

O2

O2

O2

CO2

O2

O2

O2

III) LungModels
A) Theonecompartmentlungmodel
1) Normally,arterialbloodgasesequilibratewithalveolargasesasbloodtraversespulmonary
capillaries
2) Whenventilation(VA)decreasesrelativetoperfusion(Q),thenbloodwillneitherproperly
oxygenateorunloadCO2
(a) PaO2willfallbelow100mmHg
(b) PaCO2willincreaseabove40mmHg
3) Ifthealveolusiscompletelyblocked(i.e.,thereisshunting),thenthebloodwillremainvenous
bloodandtherewillbenochangeinABGs
4) IfV>Q,thenPaO2willincreaseabove100mmHgandPaCO2willfallbelow40mmHg
(a) Ifthisistakentoextremes(i.e.,asQapproaches0andV/Qapproachesinfinity),thenPaO2will
equilibratewithPAO2(whichrepresentsthePIO2,whichequals~150mmHg)andthePaCO2
willfalltozero
B) Thetwocompartmentlungmodel
1) Thisgetsfairlyconceptual,andareviewoftherelevantlectureslidesisperhapsbest(slides4655in
AcuteRespiratoryFailureI)
2) Keyconcepts
(a) ThePaO2isdeterminedfromtheaverageO2saturation(pertheoxygen/hemoglobindissociation
curve)andnotanaverageofthePaO2fromeachvenouscomponent
(i) Thisisbecauseoxygentransportviahemoglobinissaturable
(b) V/Qmismatchcanbeclinicallycorrectedbyapplyingincreasedoxygen
(c) Shuntingcannotbeclinicallycorrectedbyapplyingincreasedoxygen
(i) ThisisbecauseoxygentransportviahemoglobinissaturablewhileCO2transportas
dissolvedcarbonicacidisnot(itiscurvilinear)
IV) TypesofRespiratoryFailure
A) Bellowsfailure
1) Noairgoesinorout,andthereisnogasexchange
2) Causes
(a) Insufficienteffort(nodrivetobreathe)
(i) Nomessagefrombrainstem
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(b) Neuromuscularsyndromes
(i) Numerousetiologies
(c) Excessworkofbreathingmusclefatigue
(i) COPD,asthma,fibrosis,obesity,etc.
(d) Inefficiencyofbellowsmechanism(effortiswasted)
(i) Flatdiaphragmwithhyperinflation,lowtidalvolume,unstablechest,etc.
3) Treatment
(a) Aggressivesupportisoftenneeded
(i) Provideairway
(ii) Supplyabreathingrate(ifnodriveispresent)
(iii)
Supportworkofbreathing
B) RespiratoryfailureduetoCOPD
1) InitialABGs
(a) PaO2=2040mmHg
(b) PaCO2=5070mmHg
(c) pH=7.207.30
(i) Oftentimes,thepHispartlycompensatedandresidessomewherebetweenacuteandchronic
acidosis
(d) Aagradientisveryhigh
2) Problem
(a) WorseningV/QmismatchcombinedwithincreasingCO2production
(b) Patientattemptstocompensatethroughmaximalventilation
(c) Increasedairwayresistance,hyperinflation,andmusclefatiguebellowsfailure
(i) Themaximumminuteventilationis~35LperliterofFEV1,andcanonlybesustainedfor
shortperiodsoftime
3) Treatment
(a) AdministeroxygentocorrectV/Qmismatch
(b) Noninvasivefacemaskventilation
(i) Fasterreductioninrespiratoryrateandheartrate
(ii) Fasterimprovementindyspneaandgasexchange
(iii)
Lesschanceofrequiringintubation(42%)
(iv)Shorterhospitalstay
(v) Lowermortality
(c) Treatbronchospasm,infection,volumeoverload,etc.
(d) Smokingcessation
4) ABGsposttherapy
(a) PaO2=5060mmHg
(i) Markedimprovement
(b) PaCO2=5570mmHg
(c) pH=7.207.30
C) Acuterespiratorydistresssyndrome(ARDS)
1) Insultinjuryabnormalphysiologysupportrepairordeath
2) Insultsincludesurgicalornonsurgicalinterventions
(a) Pneumonia,sepsis,aspiration,trauma,etc.
3) Injury
(a) Afteralagperiod,injurytothecapillariescausesincreasedpermeability,andthelungisflooded
withhighproteinfluid
4) Abnormalphysiology
15

(a) Edema,fibrosis,hypoxemia,shunting,etc.
5) Support
(a) Highpressureventilatorsandhighoxygenconcentrationshavebeenshowntopropagateinjury
(b) Positiveendexpiratorypressure(PEEP)ventilationispreferred,asitishighlybeneficial
(i) Maintainsaplateaupressureaboveatmosphericpressure
(ii) Priesthelungopentoahigherlungvolume
(iii)
IncreasesFRC
(iv)Decreasesshunt
(c) Proneventilationasopposedtosupine
D) Diffuselungdisease
1) V/Qmismatch
2) Oxygenwillcorrectthehypoxemia
E) Pulmonaryedema
1) Intrapulmonaryshunt
2) Oxygenwillnotcorrectthehypoxemia
BacterialPneumonia
I) Pathogenesis
A) Fourcategoricalmechanismsofinfection
1) Aspiration
(a) Oropharyngealsecretions
(i) Thisisthemostcommoncauseofpneumonia
(b) Stomachcontents
(c) Foreignbody
2) Aerosol
(a) Transmissionofsmall(<5m)aerosolizedparticles
(i) Persontopersontransmissionwithhighinfectivity
(b) Viruses
(c) Mycoplasma
(d) Tuberculosis
(e) Legionella
(f) Fungi
3) Hematogenous
(a) Bacteremia
(b) Viremia
(i) Varicellazoster
(ii) CMV
(c) Fungemia
(i) Histoplasmosis
(ii) Cryptococcus
(d) Miliarytuberculosis
4) Reactivation
(a) Tuberculosis
(b) Fungaletiologies
(i) Histoplasmosis
(ii) Blastomycosis
(iii)
Pneumocystis
16

B) Hostabnormalitiesthatpredisposetoinfection
1) Ineffectivecoughand/orincreasedaspiration
(a) COPD,swallowingdisorders,lungcancer,alcoholintoxication,etc.
2) Decreasedmucociliarytransport
(a) Smoking,COPD,cysticfibrosis,viralinfection,etc.
(b) Ciliopathies
3) Medications
(a) IncreasedgastricpH(histamineblockers,protonpumpinhibitors,antacids,etc.)
(b) Antipsychotics
(c) Inhaledcorticosteroids
C) Abnormalflora/pathogens
1) Virulencefactors
(a) Ciliarydysfunction/transport
(i) Chlamydophilapneumoniaeciliostatic
(ii) Mycoplasmapneumoniaecilofragmentation
(iii)
Influenzavirusdecreasedmucoustransport
(b) Proteases
(i) IgAprotease
(ii) Pneumolysin
(iii)
Neruaminidase
(iv)Hyaluronidase
(v) PantonValentineleukocidin
(c) Antibioticresistance
(i) Mycobacteriumspecies
(ii) Nocardiaspecies
(iii)
Legionellaspecies
II) ClinicalPresentation
A) Pulmonarysymptoms
1) Productivecough
2) Dyspnea
3) Pleuriticchestpain
B) Systemicsymptoms
1) Fever,chills,sweats
2) Headache,confusion
3) Myalgias,arthralgias
4) Abdominalpain,nausea,vomiting,diarrhea
C) Physicalexamfindings
1) General
(a) Fever,tachypnea,tachycardia,cyanosis,alteredmentalstatus
2) Lungs
(a) Rales
(b) Dullnesstopercussion
(c) Bronchialbreathsounds
(d) Wheezes,rhonchi,egophony
(e) Pleuralfrictionrub
D) Pathophysiology
1) DecreasedalveolarventilationV/Qmismatch(approximatesashunt)hypoxemiaincreased
PCO2
17

III) Diagnosis
A) Initialevaluation
1) CXR(goldstandard)
(a) Mustdistinguishpneumoniafrombronchitis
2) Considerspectrumofvulnerability
(a) Differentpathogensaremorelikelydependingonthepatientsoverallhealth
(b) Pneumoniaseverityindexcanbeusedtodeterminerelativerisk
B) Tests
1) Firstandforemost,considerthepatientshistory
(a) Travel,animalexposure,occupationalhazards,hobbies,medications,exposuretokids
2) Sputumexamiscontroversialintermsofutility
(a) Requireshighqualityspecimen
(i) >25WBCs
(ii) <10epithelialcells
(iii)
Processedwithin12hours
(iv)Norecentantibiotictreatment
(b) Obtainedviaseveraltechniques
(i) Bronchoscopy
(ii) Transtrachealaspiration
(iii)
Transthoracicaspiration
(iv)Lungbiopsy
3) Bloodcultures
4) Pleuralfluidanalysis
5) Analysisofotherbodilyfluids
C) Donotdelayantibiotictherapywhilewaitingforobtainmicrobialsamples!
D) Antigendetectionofpathogensisindicatedinseveralsituations
1) Legionellainfection
2) Pneumococcalinfection
3) Nasopharyngealswabforinfluenza
E) PCR(accuratewithrapidturnaround)
IV) Management
A) Syndromicapproachtocommunityacquiredpneumonia(CAP)
1) Describesspecificpathogensthatarelikelytobetheculpritgiventhepatientshistory
B) EmpiricapproachtoCAP
1) Thisisamorecommonlyadoptedmethodthatfocusesonselectingrationalantimicrobialsbasedon
specificcriteria
(a) Mostlikelyorganism
(b) Riskfactorsforantimicrobialresistance
(c) Medicalcomorbidities
C) Empirictreatmentapproachesareslightlydifferentdependingonthehealth/riskofthepatient
1) Outpatients
(a) PreviouslyhealthywithnoriskfordrugresistantStreptococcuspneumoniae(DRSP)
macrolide
(b) Comorbidities,recentantibiotictherapy,orriskforDRSPfluroquinoloneorlactam+
macrolide
2) Inpatients
(a) Fluoroquinoloneorlactam+macrolide
3) ICUpatients
18

(a) Fluoroquinoloneorlactam+macrolide
(b) RiskofPseudomonasaeruginosaantipseudomonalagent+fluoroquinolone
D) Ifpatientsarenotrespondingtotreatment,considerotherpossibilitiesandexpandtestingprotocol
1) Noninfectiouscause
(a) Therearemanynoninfectiousmimicsofpnemonia
2) Unusual/resistantorganism
3) Superinfection
4) Metastaticinfection
5) Undrainedinfection
6) Endobronchialobstruction
PleuralDiseases
I) PleuralEffusions
A) Presentation
1) Spirometryshowsrestriction
(a) DecreasedFEV1andFVC
(b) NormalFEV1/FVC
2) Increasedworkofbreathing
3) Dyspnea
4) Pleuriticchestpain
(a) Maybereferredtoshoulder
5) Cough(usuallynonproductive)
6) Physicalexamfindings
(a) Respiratorydistresswithexpandedhemithorax
(b) Dullnessonpercussion
(c) Diminishedbreathsoundsonauscultation
(d) CHF,abdominaldistentionwithascites,arthropathy,etc.
7) Imaging
(a) MeniscussignonCXR(cuppedeffusionthatobscurescostophrenicangleanddiaphragm)
(b) OpacityonchestCTthatwillmovewithgravity
(c) Pleuraleffusionsinthelungfissuresmayappearaspseudotumors
(d) Ultrasoundmayshowseparationofvisceralandparietalpleura
B) Physiologyandpathophysiology
1) Pleuralanatomy
(a) Theparietalpleurahaslargelymphaticstomaandpainnerves
(i) Thus,pleuriticpainisduetoparietalpleuralinvolvement
(ii) Thelargelymphaticstomaareresponsibleforremovingfluidfromthepleuralspace
o Starlingforcessuggestthatwithoutthesestoma,capillaryfluidwouldaccumulateinthe
pleuralspace
(b) Thevisceralpleuralackspainfibers
2) Pleuralpressure
(a) Balancebetweenelasticpressureofchestwall(outward)andlung(inward)
(b) Primarydeterminantoflungvolume
(c) Normalintrapleuralpressureis5cmH2O
(i) Thereisaverticalpressuregradient,withthemostnegativepressureintheupperlungfields
3) Pathogenesisofeffusions
(a) Noninflammatorytransudates
19

(i) Increasedhydrostaticpressure(e.g.CHF)
(ii) Reducedcapillaryoncoticpressure
(iii)
Morenegativepleuralpressure(e.g.atelectasis)
(b) Inflammatoryexudates
(i) Increasedpleuralsurfacepermeability
(ii) Increasedpleuraloncoticpressure
(c) Transudativeorexudative
(i) Impairedlymphaticdrainage(blockageofstoma,e.g.cancer)
(ii) Transdiaphragmatictransport(ascites,e.g.liverfailure)
C) Evaluation
1) Thoracentesis
(a) Aneedleispassedthroughthechestwallandintothepleuralspace
(b) Fluidiswithdrawnforanalysis
(c) Risksofbleeding,infection,andpneumothorax
2) Differentiatingtransudativeandexudativeeffusions
(a) Lightscriteriafortransudate(mustmeetallcriteria)
(i) Ratioofpleuralproteintoserumproteinis<50%
(ii) RatioofpleuralLDHtoserumLDHis<60%
(iii)
PleuralLDHvalueis<2/3oftheupperlimitofnormalserumLDH
(b) Lightscriteriaforexudate(onlyneedtomeetonecriterion)
(i) Ratioofpleuralproteintoserumproteinis>50%
(ii) RatioofpleuralLDHtoserumLDHis>60%
(iii)
PleuralLDHvalueis>2/3oftheupperlimitofnormalserumLDH
3) Imaging
(a) Loculated(walledoff,localized)effusionsuggestsanexudate
D) Causesoftransudatesandexudates
1) Causesoftransudativeeffusion
(a) CHF(typicallybilateral)
(b) Nephroticsyndrome(lowoncoticpressure)
(c) Livercirrhosis(ascitestracksacrossrighthemidiaphragm)
2) Causesofexudativeeffusion
(a) Parapneumoniccauses
(i) Thesearecausedbyabacterialpneumonia
(ii) Therearethreetypes
o Empyema=pusinpleuralspace
Treatedbydrainage+antibiotics
o Simpleparapneumoniceffusion
Treatedwithantibioticsalone
o Complicatedparapneumoniceffusion=highlyinflammatory,butnopus
Treatedwithantibiotics,butmayneeddrainageaswell
(iii)
Complications
o Bronchopleuralfistulaairandinfectionpassfromlungstopleura
o Fibrothoraxrestrictivelungdisease
(b) Pulmonaryembolism
(c) Neoplasm(e.g.,mesothelioma)
(i) Malignantmesothelioma
o Uncommonprimarycancer
o Associatedwithasbestosexposure
20

o Poorprognosis
(ii) Metastatic
o Usuallyduetoprimarylungcancer,breastcancer,orlymphoma
Reflectsunresectabledisease(akapoorprognosis)
(iii)
AlsoexhibitexudativeandlymphocyticeffusionlikeTB
(d) Rheumatologicdiseases(e.g.,rheumatoidarthritis,lupus,etc.)
(e) Tuberculosis
(i) Focalgranulomanearpleuralsurfacerupturesbacteriaintopleuralspacedelayed
hypersensitivityreactiongranulomatousreaction
(ii) Pleuralfluidwillbeexudativeandlymphocytic,butveryfewacidfastbacilliwillbepresent
o Pleuralbiopsyisoftenneededfordiagnosis
(iii)
Treatedthesameasregularpulmonarytuberculosis(combinationtherapy)
(f) Hemothorax
(i) Trauma
(ii) Neoplasm(notoften)
(iii)
Pulmonaryembolism(notoften)
(g) Chylothorax
(i) Distinctmilkappearanceduetohightriglyceridecontent
(ii) Causedbyblockageofthethoracicduct
o Mostoftenduetoneoplasminthemediastinum(e.g.,lymphoma)
II) Pneumothorax
A) Presentation
1) Symptoms
(a) Pleuriticchestpain
(b) Dyspnea
2) Examfindings
(a) Hyperresonanceuponpercussion
(b) Decreasedbreathsounds
(c) Trachealdeviationtowardsthesideofcollapse
(d) Hemodynamicinstability(iftensionpneumothorax)
3) Imaging
(a) AirpocketwithcollapsedlungonCXRandchestCT
B) Classifications
1) Primaryspontaneous
(a) Otherwisehealthyindividuals
(b) ApicalsubpleuralblebsarecommononchestCT
(c) Patientstypicallyintheir20s,smoke,andmayhaveafamilyhistory
2) Secondaryspontaneous
(a) Underlyinglungdisease(COPDismostcommon)
(b) Moreoften,thesearelifethreatening
3) Traumatic
(a) Traumaoriatrogenic
C) Management
1) Primaryspontaneous
(a) <20%ofchestcavity=observe
(b) >20%ofchestcavity=evacuateair
2) Secondaryspontaneous
(a) Evacuateair
21

3) Pleurodesisforseverecases
(a) Inducesachemical/inflammatoryreactionthatobliteratesthepleuralspacebycausingthepleura
tofibrosetogether
III) Atelectasis
A) Collapseofthelung
B) Diversecauses
1) Externalcompression
(a) Fluidinpleuraleffusion
(b) Airintensionpneumothorax
2) Inadequateventilation
(a) Collapseofentirelobe/lungdistaltoplug(mucus,foreignbody,tumor)
(b) Localizedtoasegmentorsubsegmentofalobe
C) Types
1) Complete
2) Platelike
3) Bibasilardependent
PulmonaryEmbolism
I) Introduction
A) Definition
1) Pulmonaryemboliarethrombifromthevenouscirculationthatembolizetothepulmonaryarteries
B) Epidemiology
1) Incidenceof1/1,000peryear
2) Diagnosisisdifficult
3) UntreatedPEhasahighmortality
4) Commoncauseofsuddendeathinhospitalizedpatients
C) Contributorstothrombusformation
1) Inheritedriskfactors
2) Relativeriskfactors
3) Acquiredriskfactors
(a) Virchowstriad
(i) Venousstasis
(ii) Endothelialdamage
(iii)
Hypercoagulability
II) PathophysiologicConsequencesofPE

22

A) ABGsmayshowrespiratoryalkalosis,hypoxemia,andanincreasedAagradient
1) Deadspacehaslittleeffect
2) ShuntmayincreasePaCO2
3) V/Qmismatch
(a) HighV/QunitsmaylowerPaCO2
(b) LowV/QunitsmayincreasePaCO2
B) Hemodynamicconsequences
1) Pulmonaryhypertension
2) DilationoftheRV
3) Leftwarddeviationoftheinterventricularseptum
III) ClinicalPresentation
A) Clinicalpresentationsvarygreatlyandmayincludethefollowing
1) Acuteonsetofpleuriticchestpain
2) Dyspnea
3) Hemoptysis
4) Acutecardiovascularcollapse
(a) Syncope
(b) Cardiacarrest
B) CXRfindingsarenonspecific
1) Rarelydiagnostic,asitisnormalin>20%ofcases
2) Volumeloss
3) Atelectasis
4) Patchydensity(duetoedemaandhemorrhage)
5) Localizedoligemiawithproximalpulmonaryarteryenlargement(Westermarkssign)
6) Localized,pleuralbasedtriangulardensityrepresentinganinfarct(Hamptonshump)
7) Pleuraleffusion
C) ECGfindings
1) Tachycardia
2) Ppulmonale(tall,peakedPwaves)
3) RVstrain
4) RBBB
D) ABGfindings
23

1) Hyperventilation
2) LowPaCO2
3) Normaloxygensaturation
4) PaO2maybelow,butanormalfindingdoesnotexcludePE
E) Diagnosis
1) Musthaveahighclinicalsuspicion
2) Imaging
(a) DVT
(i) Venography(contract,radionuclide,CT)
(ii) Dopplerultrasound
(b) PE
(i) Pulmonarycontrastangiogiography
(ii) V/Qlungscan(rarelyusedanymore)
(iii)
CTangiography
(iv)MRI
3) Tests
(a) Ddimer(maybeelevated)
F) Assessingseverity
1) Echo
(a) RVdilation
(b) RVhypokinesis
(c) Tricuspidregurgitation
(d) Deviationoftheinterventricularseptum
(e) Clotsenpassage
2) Hemodynamics(BPandHR)
3) CVP
4) ABG
5) Residualclotburden
(a) Dopplerultrasound
(b) Heparinconsumption
IV) Treatment
A) Preventnewclotformationwithanticoagulants
1) Heparin(unfractionatedorLMWH)
(a) Anticoagulantofchoice
(b) Rapidonsetofeffect
2) Warfarin
(a) Lesspotent
(b) Oraldosing
(c) Continuefor~3months(potentiallylonger)
3) Idraparinux
B) Lyseexistingclotswiththrombolytics
1) Urokinase
2) Streptokinase
3) Tissueplasminogenactivator
C) Preventlargeclotsfromreachingthelungs
1) Inferiorvenacavafilters
D) Removeexistingclots
1) Thrombectomy(mechanicalorsuction)
24

E) Standardtreatmentapproach
1) Beginwithheparin
2) Overlapheparinandwarfarintherapyfor~5days
3) Continuewithwarfarinfor3+months
4) AdjustwarfarindoseasneededtomaintainINRof23
F) Prevention
1) Earlyambulation
2) Gradedcompressionstockings
3) Intermittentpneumaticcompression
4) Fixed,lowdoseheparin
5) Adjusteddosewarfarin
6) IVheparin
PulmonaryHypertension
I) Introduction
A) Definitionofpulmonaryhypertension
1) Meanpulmonaryarterypressure(mPAP)>25mmHg
1
2
(a) mPAP= systolic PAP+ diastolic PAP
3
3
B) Epidemiology
1) Notmuchknown
C) Pulmonaryvasculature
1) Dualbloodsupply
(a) Bronchialcirculationfromtheaortahassystemicpressuresandlowcompliance
(b) PulmonarycirculationfromtheRVhaslowpressureandhighcompliance
2) Calculatingpulmonaryvascularresistance
P PLA
(a) R= PA
CO
(i) PPA=meanpressureinthepulmonaryartery
(ii) PLA=meanpressureintheleftatrium
(iii)
CO=cardiacoutput(L/min)
(b) Thetranspulmonarygradient(TPG)isnormally<10mmHg
(i) TPG=mPAPPCWP
D) Exercise
1) Duringexercise,COincreaseswhilepulmonarypressuresremainrelativelyconstant
2) Thisisbecausethepulmonaryvasculatureisbothdistendableandabletorecruitotherwise
underperfusedcapillarybeds
E) Pathologicalchangeswithpulmonaryhypertension
1) Pulmonaryarteriesthickenandnarrow
(a) Thickeningmaybecausedbyanimbalancebetweenvasoconstrictiveandvasodilativepathways
(i) Theendothelinpathwaypromotesvasoconstrictionandsmoothmusclecellproliferationand
isupregulatedindisease
(ii) NOandprostacyclinpathwaysopposetheendothelinpathway,inducingvasodilationand
antiproliferation
2) Unaffectedpulmonaryarteriesareforcedtodilateinresponsetoincreasedpressureandflow
3) TheRVdilatesandhypertrophiesinresponsetotheincreasedpressure
F) Clinicalfindings
25

1) Symptoms
(a) Dyspnea(6090%)
(b) Fatigue(19%)
(c) Chestpain(7%)
2) Physicalexam
(a) ProminentP2
(b) RVH(prominentAwaveinjugularvenouspulse)
(c) Rightsidedheartfailure
(i) S3
(ii) Tricuspidinsufficiencywithholosystolicmurmur
(d) Hepaticcongestion
(e) Peripheraledemaand/orascites
II) ClassificaitonsofPulmonaryHypertension
A) Pulmonaryarterialhypertension(PAH)
1) Histopathology
(a) Endothelialproliferation
(b) Intimalfibrosis
(c) Medialandsmoothmusclecellhypertrophy
(d) Insituthrombosis
2) Causes
(a) Idiopathic
(b) Heritablemutations
(i) BMPR2(bonemorphogenicproteinreceptor2)
o Autosomaldominantwithincompletepenetrance
o Presentin70%offamilialcasesofpulmonaryhypertension
(ii) ALK1(activinreceptorlikekinasetype1)
(iii)
Serotonintransporter
(c) Drugandtoxininduced
(d) Collagenvasculardiseases
(e) HIVinfection
(f) Portalhypertension
(g) Congenitalheartdiseases
(h) Schistosomiasis
(i) Chronichemolyticanemia
(j) Pulmonaryvenoocclusivedisease(PVOD)and/orpulmonarycapillaryhemangiomatosis(PCH)
B) Pulmonaryhypertensionowingtoleftheartdisease
1) Mostcommoncauseofpulmonaryhypertension
2) Causes
(a) Increasedleftatrialpressure
(i) Leftheartsystolic/diastolicdysfunction
(ii) Leftheartvalvulardisease
(b) Increasedpulmonaryvascularresistance
C) Pulmonaryhypertensionowingtolungdiseasesand/orhypoxia
1) Alveolarhypoxia
(a) Hypoxiavasoconstrictionincreasedvasculartonedecreasedvascularbed
2) Exemplarydiseases
(a) COPD
(b) Interstitiallungdisease
26

(c) Sleepdisorderedbreathing(apnea)
D) Chronicthromboembolicpulmonaryhypertension(CTEPH)
1) Chronicpulmonaryembolicreatestructuralblockagesthatincreasepressure
E) Pulmonaryhypertensionwithunclearmultifactorialmechanisms
1) Hematologicdisorders
(a) Chronicmyeloproliferativedisorders
2) Systemicdisorders
(a) Sarcoidosis
3) Metabolicdisorders
(a) TypeIaglycogenstoragedisease
4) Miscellaneous
(a) Tumorobstruction
(b) Mediastinalfibrosis
(c) Endstagerenaldisease
III) Diagnosis
A) Basedonsuspicionofpulmonaryhypertension,onecanprogressthroughadiagnosticworkflow
1) Echocardiogram
(a) Leftheartdisease
(b) Congenitalheartdisease
2) CXR,PFTs,andCT
(a) Obstruction
(b) Restriction
(c) Parenchymaldisease
3) V/Qscan,CTangiogram,andpulmonaryangiogram
(a) Chronicthromboembolicdisease
4) Sleepstudyandovernightoximetry
(a) Sleepapnea
5) Antibodytests
(a) SLE
(b) Scleroderma
6) Liverfunctiontests
(a) Portopulmonaryhypertension
7) HIVtesting
(a) HIV
8) Cardiaccatheterization
(a) Shuntorheartdisease
9) Ifallarenegative,thepulmonaryhypertensionisclassifiedasidiopathic
IV) Treatment
A) Earlytreatmentisdirectedattheunderlyingcauses
1) Pulmonaryarterialhypertension
(a) Treatunderlyingheartdisease
2) Pulmonaryhypertensionowingtoleftheartdisease
(a) Treatunderlyingcardiomyopathy
(b) Replacevalve
3) Pulmonaryhypertensionowingtolungdiseasesand/orhypoxia
(a) Treathypoxia
(i) Longtermadministrationofoxygenmaybebeneficial
(b) Optimizelungdisease
27

(c) Treatsleepapnea
(i) Weightloss
(ii) CPAP(continuouspositiveairwaypressure)
(iii)
Correctiveairwaysurgery
(iv)Tracheostomy
4) Chronicthromboembolicpulmonaryhypertension
(a) Thromboendarterectomy
(b) Anticoagulation
B) Advancedtreatmentisdirectedatthepulmonaryhypertensionitself
1) Patientfunctionalclasses(WHO)
(a) Inolimitationsonphysicalactivity
(b) IIordinaryphysicalactivitycausessymptoms
(c) IIIlessthanordinaryphysicalactivitycausessymptoms
(d) IVsymptomspresentatrest
2) Treatedwithpulmonaryvasodilators
(a) Calciumchannelblockers(nifedipineanddiltiazem)
(b) Endothelinreceptorantagonists
(c) NOdonators
(d) Prostacyclintherapy
3) Anticoagulation
4) Lungtransplantation
InterstitialLungDisease
I) Introduction
A) Features
1) Noninfectious,nonmalignantprocessofthelowerrespiratorytract(likelyinanimmune
compromisedhost)
2) Mayormaynothavegranulomatousfeatures
3) Interstitialinflammationandfibrosis
B) Pathophysiology
1) Decreasedcompliance
(a) Increasedrespiratoryrate
(b) Increasedworkofbreathing
(c) Spirometryvaluesaredecreasedinsuchawaythattheratiobetweenthemispreserved
2) Decreasedlungvolume
3) Diffusionimpairment
(a) Decreasedsurfaceareaforgasexchange
(b) DecreasedDLCO
4) Impairedgasexchange
(a) Hypoxemia
(b) V/Qmismatch
5) Pulmonaryhypertensionandcorpulmonale
(a) Obliterationofpulmonaryvasculaturebyafibroticprocess
(b) Hypoxemiareactivevasoconstriction
II) ClinicalFeatures
A) History
1) Dyspnea
28

2) Cough(nonproductive)
B) Physicalexam
1) Basilar,inspiratorycrackles
2) Clubbing
3) Skin/jointchanges
4) Symptomsofcorpulmonale
C) Imaging
1) Reticularchanges(meshlike,interlacingshadows)
2) Reticulonodularchanges(reticularchangeswithfinenodules)
3) Honeycombing(coarsereticularandcysticchanges)
4) Groundglassopacity(vesselsarenotobscured)
III) Differentialdiagnosis(DISCO)
A) Drugandradiationinduced
1) MitomycinC,methotrexate,amiodarone,etc.
2) Characteristicallylarge,atypicaltypeIIpneumocytes
3) Radiationinjuryistypicallyconfinedtowellcircumscribedareas,creatingverystraightlinesof
demarcatedinjuryonCXR
B) Idiopathic
1) Pathologyiscalledusualinterstitialpneumonia
2) CXRshowsreticular,interstitialinfiltrateswithhoneycombing
3) Temporalheterogeneity
(a) Densecollagenousfibrosisisoftenfoundincloseproximitytoactiveinflammation
(b) Fociofrapidlyproliferatingfibroblastsmaybefound
4) Theonlydefinitivetreatmentislungtransplant
C) Sarcoid
1) SystemicdisordercharacterizedbyTcellandmacrophageactivation
(a) Mostfrequentlyaffectsthelungs
2) Characterizedbynoncaseatinggranulomas
3) PresentswithLofgrenssyndrome
(a) Erythemanodosum
(b) Arthralgias
(c) Uveitis
(d) StageICXR(bilateralhilarlymphadenopathy)
4) SarcoidCXRstagingsystem
(a) Stage0=normal
(b) StageI=bilateralhilarlymphadenopathy(BHL)
(c) StageII=BHL+infiltrates
(d) StageIII=infiltratesalone
(e) StageIV=fibrosis
5) Treatwithsteroidsifthediseasedoesnotspontaneouslyresolve
D) Connectivetissuedisorders
1) Scleroderma
2) Rheumatoidarthritis
3) SLE
4) Polymyositis/dermatomyositis
E) Occupationalandenvironmental
1) Inorganic(metals)andorganic(allergens)instigators
2) Asbestosis
29

(a) PleuralplaquesonCXT/CT
(b) Ferruginousbodiesonmicroscopy
3) Hypersensitivitypneumonitis
(a) HoneycombingonCT
(b) Looselyformedgranulomasonmicroscopy
RespiratoryComplicationsofImmunodeficiency
I) Introduction
A) Thelungandtheimmunocompromisedstate
1) Environmentalcontactoccursviathelung,skin,andGItract
2) Thelunginterfaceisthe#1siteofinfection
3) Broaderdifferentialdiagnosisforinfiltrates
4) PMH,occupational,andtravelhistoriesareespeciallyimportant
5) Prophylacticantimicrobialsarecrucialinpreventinginfection
B) Increasedriskofnewinfectionandreactivationofoldinfection
1) ReactivationisprimarilyaconsequenceofTcelldysfunction
II) LossofNeutrophilFunction(HSCT)
A) Hematopoieticstemcelltransplantation(HSCT)
1) Pulmonarycomplicationsareobservedinupto60%ofpatients
(a) Pneumoniaistheleadinginfectiouscauseofdeathinsuchpatients
(b) Riskfactorsforinfection
(i) Extendedneutropenia
(ii) Medicalimmunosuppression(e.g.corticosteroids)
B) Aspergillus
1) Opportunisticfungalpathogenthatpresentsashyphaeininfectedtissue
2) Normaltissueisdefendedagainstinfectionbyfunctioningneutrophils
3) Incasesofsevereneutrophildysfunction,aninvasiveformofaspergillosiscandevelop
(a) Observedin1015%ofHSCTpatients
(b) Canspreadhematogenouslytoothersolidorgans
(c) Maycausetracheobronchitis
(d) Treatedwithavarietyofantifungalagentsandsurgicalresection(ifnecessary)
4) Chronicpulmonaryaspergillosismaydevelopinpatientswithunderlyinglungdiseaseandmild
immuneimpairment
(a) Spectrumofoverlappingdiseases
(b) Cough,weightloss,fatigue,hemoptysis
(c) Cavitation,fibrosis,focalpneumonia,aspergilloma
5) AllergicbronchopulmonaryaspergillosisiscausedbyIgEandIgGreactionsagainstaspergillus
antigens
(a) Seenprimarilyinpatientswithasthma
(b) Productivecoughwithbrownmucus/fungusplug
C) Mucormycosis
1) Invasivelungdiseasesimilartoaspergillosis
2) Strongpropensitytoprogresstoinvasivesinusdisease
D) Candidiasis
1) Uncommoncauseofpneumoniaandpulmonaryinfection
2) Tcelldeficiencymucosalinfection(e.g.,thrush)
3) Neutrophildeficiencydeeptissueinfection(e.g.,dermis)
30

III) LossofCellMediatedImmunity(HIVandAIDS)
A) Pathogenesis
1) HIVbindstolungcellsthathaveCD4+receptors
(a) THcellsarethemostimportant,thoughmacrophagesarealsovulnerable
2) LysisofinfectedTHcellsleadstolymphocytopenia
(a) CD4+Tcellcounts<200cells/ListhedefinitionofAIDS
(b) SpecificopportunisticinfectionsmayalsodefineAIDS
3) Lymphocytopeniaproducesseveralconsequences
(a) Decreasedmacrophageactivation
(b) Impairedcellmediatedimmunity
(c) Decreasedhumoralimmunity
B) PrinciplesofHIVinfection
1) MustconsiderHIVinfectionwhenpresentedwithanydiffuseorpoorlyresponsivepneumonia
2) Riskfactors
(a) Unsafesexwithinfectedpartner
(b) IVdruguse
(c) Bloodtransfusions(rare)
3) Highlyactiveantiretroviraltherapy(HAART)
(a) ReducesrateofCD4+Tcelldecline
(b) Lowersviralload
(c) IncreasesefficacyofTcellimmunity
(d) Notcurative
C) Pneumocystisjiroveci
1) Consideredafungus(butnotamoldlikeaspergillus)
2) DamagestypeIpneumocytes
(a) Exudatesinalveolihypoxemia
3) Presentsasanatypicalpneumonia(pneumocystispneumonia)
(a) Slowprogressionoverweeks
(b) Nonproductivecough,fever,dyspnea
(c) CXRshowsdiffusebilateralinfiltrates
4) Diagnosis
(a) Bronchoalveolarlavage(BAL)samplesshowfoamyalveolarcasts
(b) Silverstainordirectfluorescentantibody(DFA)detectionofcentralorganisms
(c) Groundglassimaging
5) Treatwithtrimethoprim+sulfamethoxazole
(a) Addcorticosteroidsifthepatientishypoxemic
(b) Asimilartherapycanbeusedprophylacticallyinimmunocompromisedpatients
IV) OverlappingImmunosuppressedStates(SolidOrganTransplantation)
A) Solidorgantransplantation
1) Requireschronicimmunosuppressionofbothneutrophilandcellmediatedlines
B) Nocardiosis
1) Nocardiaisafilamentous,gram+,branchingrod
2) Themajorityofcasesareobservedinimmunocompromisedhosts
(a) Neutrophilsandmacrophagestypicallyinhibitgrowthandpreventspread
(b) Cellmediatedimmunitytypicallyfacilitateskilling
3) ProgressestopneumoniaandthendisseminatestotheCNSandskin
V) GeneralImmunosuppression(Medications)
A) Routinecommunityacquiredpneumoniaandrespiratoryviruses
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1) Immunocompromisedindividualswillbeinfectedbyroutineorganismsaswellasresistant
organisms
2) RSV,influenza,parainfluenza,adenovirus,etc.
B) Mycobacteriumtuberculosis
1) TuberculosisistheleadingopportunisticinfectioninAIDSpatientsindevelopingnations
2) ItisuncommoninHSCT,butstillhigherthaninthegeneralpopulation
3) Thereisagreaterriskofextrapulmonarydiseaseandadenopathyintheimmunosuppressed
4) Treatmentissimilartothegeneralpopulation
C) Cytomegalovirus(CMV)
1) Commonlyassociatedwithorgantransplantation
2) Infectionisprimarilytheresultofreactivationintheimmunocompromisedhost
Bronchiectasis
I) MucociliaryClearance
A) Normalcomponents
1) ViscousfluidoflowpH(~6.8)
2) Ciliarybeating
(a) Normalciliapossessinner/outerdyneinarms,nexinlinkers,andacentralmicrotubulepair
3) Barrierfunctionofmucus
4) Tightjunctionsofepithelialcells
B) Reversibleimpairments
1) Viralinfections
2) Cigarettesmoke
II) Bronchiectasis
A) Features
1) Chronicdilationofbronchiorbronchioleswithairwaywallthickeningresultingfromairway
inflammationorobstruction
2) Manifestswithchroniccough,excesssputumproductions,malaise,andrecurrentchestinfections
3) Manypatientshaveairflowobstruction,indicatedbyPFTsandflowvolumeloops
B) ChestCTisthegoldstandardfordiagnosis
C) Threebroadtypesofbronchiectasis
1) Cysticfibrosis(CF)bronchiectasis
2) NonCFbronchiectasis
(a) Almostallothercauses
3) Tractionbronchiectasis
(a) Airwaysaretetheredopenasopposedtohavingaprimarydiseaseoftheairwaysthemselves
(b) Typicallyseenininterstitiallungdisease
D) Pathogenesis
1) Injurytoairwayinflammationand/orinfection
(a) Impairedmucociliaryfunction
(b) Impairedhostdefense
(c) Airwayobstruction
2) Irreversibledilationofairways
(a) Colonizationbypathogenicorganisms
(i) Pseudomonasaeruginosaisespeciallyimportant
(ii) Ongoinginflammationmucosaledema,ulceration,cratering,neovascularization
(iii)
Recurrentinfectiousflares
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III) DefectsinMucociliaryClearance
A) Primaryciliarydyskinesia
1) Autosomalrecessivemutationsinnormalciliacomponentry(e.g.,Kartagenerssyndrome)
2) Presentswithchronicsinusitis,bronchiectasis,infertility,andsitusinversus(50%)
B) Cysticfibrosis(CF)
1) AutosomalrecessivemutationsinCFTRgene
(a) Encodesacrucialchloridechannel
2) Lossofthefluidlayerthatnormallybathestheciliaallowstheoverlyingmucuslayertosinkdown
andhinderciliamovement
3) Transportanomaliesalteredairwaysecretionsinfectioninflammationtissuedamage
4) Mediansurvivalis~37.5years
5) Diagnosis
(a) Sweattest(goldstandard)
(b) Genotyping
(c) Newbornscreening
6) Requiresmultidisciplinarycare

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