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CHRONICOBSTRUCTIVE AIRWAY
Lung:Normalhistology
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FVC Forced Vital Capacity This is the volume of air that can forcibly be blown out after fullinspiration, measured in liters.
FEV1 Forced Expiratory Volume in 1Second
This is the maximum volume of air that can forcibly blow out inthe first second during the FVC manoeuvre, measured in liters.Along with FVC it is considered one of the primary indicators oflung function.
FEV1/FVC FEV1% This is the ratio of FEV 1 to FVC. In healthy adults this should beapproximately 7580%.
PEF Peak Expiratory Flow This is the maximal flow (or speed) achieved during themaximally forced expiration initiated at full inspiration, measuredin liters per second.
FEF 2575% or2550%
Forced Expiratory Flow 2575%or 2550%
This is the average flow (or speed) of air coming out of the lungduring the middle portion of the expiration (also sometimesreferred to as the MMEF, for maximal mid-expiratory flow).
FIF 2575% or 2550%
Forced Inspiratory Flow 2575%or 2550%
This is similar to FEF 2575% or 2550% except the measurement istaken during inspiration.
FET Forced Expiratory Time This measures the length of the expiration in seconds.
TV Tidal volume During the respiratory cycle, a specific volume of air is drawn intoand then expired out of the lungs. This volume is tidal volume.
TLC Total Lung Capacity Maximum volume of air present in the lungs. Effectively the VitalCapacity plus residual volume.
TLCO Diffusing Capacity The carbon monoxide uptake from a single inspiration in astandard time (usually 10 sec).
MVV Maximum VoluntaryVentilation
A measure of the maximum amount of air that can be inhaled andexhaled in one minute, measured in liters/minute.
IIncreased resistance to outflowncreased resistance to outflow
COPD: Characteristics
--
Significantly reduced FEV1secSignificantly reduced FEV1sec due todue to-- Increased resistance to outflowIncreased resistance to outflow
-- Decreased elasticity and increaseDecreased elasticity and increasecompliancecompliance causedcaused byby damage o f e l as t i c damage o f e l as t i c
t i ssue i n the pu lm ona ry i n te rs t i t i umt i ssue i n the pu lm ona ry i n te rs t i t i um
RReduced FVCeduced FVC-- Due toDue to decreased elasticity and increaseddecreased elasticity and increased
compliancecompliance ReducedReduced FEV1sec/ FVCFEV1sec/ FVC Increased TLC and RV (esp. emphysema)Increased TLC and RV (esp. emphysema)
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COPDCOPD
ChronicbronchitisandemphysemaChronicbronchitisandemphysema
HavecommonetiologyHavecommonetiology:tobaccosmoking(90%):tobaccosmoking(90%)
ChronicbronchitisproducesmoreprominentChronicbronchitisproducesmoreprominentobstructionobstruction
LeadtosamecomplicationsLeadtosamecomplications
CHRONIC BRONCHITIS
DEF:persistentproductivecough,producingmucoidsputum
foratleast3consecutivemonthsinatleast2consecutiveyears
intheabsenceofspecificlungdiseases.
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Etiology - SMOKING
Irritationfromcigarettesmokestimulatesmucusgland,
Thesechangespredisposethepatientstorepeatedrespiratoryinfection whichmayaggravatethechronicbronchitis.
Etiology AIR POLLUTION
Pollutantsintheairthatmaypossiblyaffectthelungs
includesulphuroxides,nitrogenoxides,andvarious
hydrocarbons.
At
present
there
is
no
consensus
on
a
pollutant
concentration thatincreasestheriskofchronicbronchitis.
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Simple chronic bronchitisSimple chronic bronchitis: productive cough: productive cough
without evidence of airflow obstructionwithout evidence of airflow obstruction
Classification
Chronic asthmatic bronchitisChronic asthmatic bronchitis with intermittentwith intermittent
bronchospasm and wheezingbronchospasm and wheezing
Chronic obstructive bronchitis (bronchiolitis)Chronic obstructive bronchitis (bronchiolitis)
small airways (small airway disease)small airways (small airway disease)
MacroscopicMacroscopic
Morphology
-- Hyperaemia and swelling of bronchial mucosaHyperaemia and swelling of bronchial mucosa-- Mucinous or mucopurulent secretionsMucinous or mucopurulent secretions
HistologyHistology-- H y p e r t r o p h y o f s u b m u c o sa l m u c ou s g l a n d s H y p e r t r o p h y o f s u b m u c o sa l m u c ou s g l a n d s ::
Increased Reid index (N=0.4):Increased Reid index (N=0.4): ratio of theratio of the thickness of thethickness of themucous glands to the thickness ofmucous glands to the thickness of the wall between the epitheliumthe wall between the epitheliumand the underlyingand the underlying cartilagecartilage
-- Metaplasia of goblet cell in bronchial liningMetaplasia of goblet cell in bronchial lining
-- Inflammatory infiltrationInflammatory infiltration
-- SclerosisSclerosis
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Chronic Bronchitis
Chronic Obstructive Bronchioli tisChronic Obstructive Bronchioli tis
AlsoknownassmallairwaydiseaseAlsoknownassmallairwaydisease
HistologyHistology
GobletcellmetaplasiaGobletcellmetaplasia ((excessivemucusexcessivemucusproductionproduction mucusplugs) mucusplugs)
InflammationInflammation
SmoothmusclecellhyperplasiaSmoothmusclecellhyperplasia
LumennarrowingLumennarrowing airwayobstructionairwayobstruction
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Pathology
Thelungsareexpandedandvoluminous duetoairtrapping.
Thediaphragmmaybeflattened ordisplaceddownwards.
Theemphysematousareasarepaler thantherestofthelungandcontainslittleblood.
Thelungspitonpressure owingtothelackofelasticity.
Microscopically,thereislossofalveolarseptawithenlargementofairspaces.
Emphysema
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EmphysemaEmphysema
Normal alveoliNormal alveoli
Proteases and Antiproteases in P athogenesisProteases and Antiproteases in P athogenesisof Emphysemaof Emphysema
MetabolismofelastictissuedependsonMetabolismofelastictissuedependson ro e nase e as asero e nase e as ase
Antiproteinase(Antiproteinase(11ATAT antitrypsin)antitrypsin)
AntitrypsinAntitrypsin is
coded
by
is
coded
by
PiPi(proteinase
inhibitor)
locus
on
chr.
14(proteinase
inhibitor)
locus
on
chr.
14 TerminologyTerminology
orma a e eorma a e e
NormalgeneNormalgene PiMMPiMM
MutatedgenewithlowMutatedgenewithlow11ATATactivityactivity PiZZPiZZ
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Centrilobular emphysema
lobules
The respiratory bronchioles are primarily
involved while the alveolar ducts and alveoliat the periphery of the lobule are
unaffected.
Etiopathogenesis ofEtiopathogenesis ofCentroacinar EmphysemaCentroacinar Emphysema
Impaction ofImpaction ofsmoke particlessmoke particles in the wallin the wall
of respiratory bronchioliof respiratory bronchioliChemotaxis and activation ofChemotaxis and activation ofneutrophilsneutrophilsand macrophagesand macrophages
rr Damage of elastic fibresDamage of elastic fibres
Dilation of respiratory bronchioliDilation of respiratory bronchioli
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Panlobular emphysema
theterminalbronchiolesinarelatively
uniformmanner.
Thisformisassociatedwithalpha1antitrypsindeficiency
PiZZ enot ePiZZ enot e
Etiopathogenesis ofEtiopathogenesis ofPanacinar EmphysemaPanacinar Emphysema
LowLow 11--AT levelAT level
Uncontrolled protease activityUncontrolled protease activity
Dama e of elastic fibresDama e of elastic fibres
Dilation of respiratory bronchioli,Dilation of respiratory bronchioli,
alveolar ducts and sacsalveolar ducts and sacs
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Pathogenesis of Emphysema -
Consequence of: protease- anti-protease imbalance
oxidant- antioxidant imbalance
MorphologyMorphology MacroscopicMacroscopic
LocationLocation CentroacinalemphysemaCentroacinalemphysema:upperlobes:upperlobes
PanacinaremphysemaPanacinaremphysema:entirelungs,more:entirelungs,moreprominentinthelowerlobesprominentinthelowerlobes
Overinflation,grosslyvisibleairspacesOverinflation,grosslyvisibleairspaces
Apicalblebsandbullae(centroacinarApicalblebsandbullae(centroacinar
HistologyHistology
ThinninganddestructionofalveolarwallThinninganddestructionofalveolarwall
Largeairspaces(confluentalveoli)Largeairspaces(confluentalveoli)
ReducednumberofalveolarcapillariesReducednumberofalveolarcapillaries
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Centroacinar EmphysemaCentroacinar Emphysema
Centroacinar EmphysemaCentroacinar Emphysemawith Bullaew ith Bullae
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CentroCentro--acinar Emphysemaacinar Emphysema
PanPan--acinar Emphysemaacinar Emphysema
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Obstruction inObstruction inEmphysemaEmphysema
1.1. LossofelasticrecoilLossofelasticrecoil
2.2. DuringexpirationairistrappedinthealveoliDuringexpirationairistrappedinthealveoli
3.3. Effortstoexhale(accessorymuscles)Effortstoexhale(accessorymuscles)
..
5.5. Compressionoflowerairways(bronchioli)Compressionoflowerairways(bronchioli)
6.6. NarrowingofbronchiolarlumenandobstructionNarrowingofbronchiolarlumenandobstruction
Arterial Blood GasesArterial Blood Gases
..
2.2. MildhypoxemiaMildhypoxemia atrest,worseningwithexercisesatrest,worseningwithexercises
3.3. Activationof
breathingActivation
of
breathing
4.4. Noormildhypocapnia(Noormildhypocapnia(nofibrosis,preserveddiffusionnofibrosis,preserveddiffusion))
respiratoryalkalosisrespiratoryalkalosis
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Clinical CorrelatesClinical Correlates
Dyspnea(insidiousbutsteadilyprogressive)Dyspnea(insidiousbutsteadilyprogressive)
HyperventilationHyperventilation
PursinglipsanduseofaccessorymusclesPursinglipsanduseofaccessorymuscles
BarrelchestandwBarrelchestandweightlosseightloss
ComplicationsComplications
Respiratoryfailure(late,butsevere)Respiratoryfailure(late,butsevere)
NonNonventilatoryrespiratoryfailureventilatoryrespiratoryfailure
EndEndstage:stage:respiratoryacidosisrespiratoryacidosis
RSHF(corpulmonale)RSHF(corpulmonale)
Pneumothorax(bullaerupture)Pneumothorax(bullaerupture)
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Conditions Related toEmphysema
after surgical resection of a lobe or lungafter surgical resection of a lobe or lung
Senile emphysema (overinflation)Senile emphysema (overinflation) due todue to
ageage--related loss of lung elastic tissuerelated loss of lung elastic tissue
Obstructive emphysema (overinflation)Obstructive emphysema (overinflation)
after subtotal obstruction by a tumour or foreignafter subtotal obstruction by a tumour or foreigno yo y
Mediastinal ( iMediastinal (interstitial) emphysemanterstitial) emphysema thethe
entrance of air into the lung interstitium,entrance of air into the lung interstitium,
mediastinum and/or subcutaneous tissuemediastinum and/or subcutaneous tissue
Bronchial Asthma Adiseasecharacterisedbyparoxysmalnarrowing ofthe
,
resultoftreatment.
Clinically:episodicdyspnoea,cough,wheezing
Types: Extrinsicasthma
Intrinsicasthma
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- Develops early in life
Extrinsic Asthma
- Induced by exposure to an extrinsic Ag
hou se dus t , po l lens , fun ga l spor es , m i lk ,
eggs , f i sh , cerea ls , nu t s and , choco la te
- Associated allergic manifestations:rh in i t i s , eczema , u r t i ca r ia
- Positive family history
Mechanism of ExtrinsicMechanism of ExtrinsicAsthmaAsthma
TypeIHypersensitivityReactionTypeIHypersensitivityReaction
11 Underlyingabnormality:predominantactivationofUnderlyingabnormality:predominantactivationofTHTH22
22 ReleaseofReleaseofILIL4andIL4andIL55
33 ProductionofProductionofIgEIgE byplasmacells;activationofbyplasmacells;activationofmastcellsandmastcellsand
eosionophilseosionophils
4.4. Ag+IgE+mastAg+IgE+mast cellcell
5.5. MastcellMastcelldegranulationdegranulation
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Mechanism of Extrinsic AsthmaMechanism of Extrinsic Asthma(Cont.)(Cont.)
6.6. EarlyphasereactionEarlyphasereaction
.. receptorsreceptors
2.2. BronchoBronchoconstriction,edemaandmucussecretionconstriction,edemaandmucussecretion
7.7. LateLatephasereactionphasereaction (beginsin4(beginsin4 8hoursandpersists128hoursandpersists12 2424hours)hours)
1.1. Mastcell(andother)mediatorsMastcell(andother)mediators induceinflux
of
all
induce
influx
of
all
typesofWBCs(esp.eosinophils)typesofWBCs(esp.eosinophils)
2.2. AcuteinflammatoryreactionAcuteinflammatoryreaction
MajorbasicproteinMajorbasicprotein fromeosionophilsfromeosionophils epithelialepithelialdamageandbronchoconstictiondamageandbronchoconstiction
Mediators in ExtrinsicMediators in ExtrinsicAsthmaAsthma
Name Action
LTC4 Prolon ed Bronchoconstriction
LTD4
LTE4
Vascular permeability
Mucus secretion
Acetylcholine Stimulation of M-receptors Bronchospasm
Histamine Bronchoconstriction
PGD2 Bronchoconstriction
Vasodilation
PAF Aggregation of platelets histamine &serotonin release
IL-1, TNF, IL-6, NO,eotaxin,neuropeptides,bradykinin
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Prognosis
Theoverallprognosisforextrinsicasthmaisgood
Wellcontrolledcases,theattacksusuallyceaselaterin
childhoodoradolescence
Occasionally,asevere
paroxysm
can
result
in
respiratory
.
Viral infectionViral infection
Intrinsic Asthma
AspirinAspirin
LowLow--molecularmolecular--weight occupationalweight occupational--relatedrelatedsubstancessubstances
-- HistamineHistamine--like substanceslike substances-- Substances affecting autonomous NSSubstances affecting autonomous NS-- Irritant ases e. ., NH3, SO2Irritant ases e. ., NH3, SO2
-- Plastic fumesPlastic fumes
Physical exercisesPhysical exercises
ColdCold Psychological stressPsychological stress
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Mechanisms of IntrinsicMechanisms of IntrinsicAsthmaAsthma
ExactmechanismisunknownExactmechanismisunknown
HypotheticalmechanismsHypotheticalmechanisms
DecreasedthresholdofDecreasedthresholdofvagalreceptorsvagalreceptors inin
bronchialmucosa(viralinfection)bronchialmucosa(viralinfection)
Deregulatedproduction
of
Deregulated
production
of
arachidonicacidarachidonicacid
metabolitesmetabolites
DirectstimulationofDirectstimulationofvagalreceptorsvagalreceptors (gases,(gases,
fumes,coldair)fumes,coldair)
Macrosco icMacrosco ic
Morphology
-- Over distendedOver distended lungs (over inflation)lungs (over inflation)
-- Occlusion of bronchial tree by mucinous plugsOcclusion of bronchial tree by mucinous plugs
Histology of bronchial treeHistology of bronchial tree-- Mucus plugs (with eosinophils)Mucus plugs (with eosinophils)
--
-- Submucosal gland hypertrophySubmucosal gland hypertrophy
-- Inflammatory infiltration (esp. eosinophils)Inflammatory infiltration (esp. eosinophils)
-- Smooth muscle cell hypertrophySmooth muscle cell hypertrophy
-- Basement membranes thickeningBasement membranes thickening
NB: al veo l i a re no t dam aged NB: al veo l i a re no t dam aged
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Bronchial AsthmaBronchial Asthma
Eosinophils in Mucus P lug and BronchialEosinophils in Mucus P lug and BronchialMucosaMucosa
M u c u s P l u gM u c u s P l u g
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Mucin Cast in Bronchial Asthma
Genetics of asthmaGenetics of asthma
ADAMADAM33:matrixmetalloproteinase frombronchialsmooth33:matrixmetalloproteinase frombronchialsmooth
ADAMADAM33pleomorphism33pleomorphism bronchialSMChyperplasiaandbronchialSMChyperplasiaandsubendothelialfibrosissubendothelialfibrosis
GSTM1GSTM1 IL10,IL4,IL4R,IL13IL10,IL4,IL4R,IL13
TNFTNF
NOD1NOD1
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Clinical CourseClinical Course
AttacksAttacks
ronc ospasmronc ospasm
OverinflationOverinflation
ClinicalpresentationClinicalpresentation WheezingWheezing
SeveredyspneaSeveredyspnea
StatusastmaticusStatusastmaticus:potentiallyfatalnonreletingattack(days,:potentiallyfatalnonreletingattack(days,rarelyrarely weeks)weeks)
Intervalsbetweenattacks:nomanifestationsIntervalsbetweenattacks:nomanifestations
Laboratory DiagnosisLaboratory Diagnosis
SputumcytologySputumcytology
Curshmannsspirals:twistedmucousplugsCurshmannsspirals:twistedmucousplugs
admixedwithsloughedepitheliumadmixedwithsloughedepithelium
EosinophilsEosinophils
CharcotCharcotLeyden
crystals:
crystalloids
of
eosinophil
Leyden
crystals:
crystalloids
of
eosinophil
proteinsproteins
ElevatedeosinophilcountinperipheralbloodElevatedeosinophilcountinperipheralblood
ElevatedserumIgEElevatedserumIgE
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Curshman Spirals andCurshman Spirals andCharcotCharcot--Leyden CrystalsLeyden Crystals
BronchiectasisBronchiectasis
DefinitionDefinition:b:bronchiectasisisanirreversibleronchiectasisisanirreversibledilatationofthebronchiwithformationofdilatationofthebronchiwithformationof
largespacesorcavitieslargespacesorcavities
EtiologyEtiology
DestructionofmusclesandelasticsupportingDestructionofmusclesandelasticsupportingtissuetissue resultingfromorassociatedwithresultingfromorassociatedwith
ChronicnecrotizinginfectionChronicnecrotizinginfection
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Predisposing LesionsPredisposing Lesions
BronchialobstructionBronchialobstruction:infectiondistaltoobstructionwith:infectiondistaltoobstructionwithsubsequentdestructionofbronchialwallsubsequentdestructionofbronchialwall
TumorTumorForeignbodyForeignbodyMucusplugMucusplug
NecrotizingorsuppurativepneumoniaNecrotizingorsuppurativepneumonia (TB,(TB,S.aureus,S.aureus,H.Influenzae,Psedomonas)H.Influenzae,Psedomonas)
PurulentrhinosinusitisPurulentrhinosinusitis:as irationofbacteria:as irationofbacteria CysticfibrosisCysticfibrosis:obstructionbyviscidmucus:obstructionbyviscidmucus Immunodeficiency(IgA):Immunodeficiency(IgA): repeatedbacterialinfectionrepeatedbacterialinfection KartagenersyndromeKartagenersyndrome
MorphologyMorphology
LowerlobesLowerlobes
Bronchioliextendtothepleura(innormalBronchioliextendtothepleura(innormallung,2lung,2 3cmperipleuralzoneisfreeof3cmperipleuralzoneisfreeof
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BronchiectasisBronchiectasis
BronchusBronchus
Bronchiectasis w ithBronchiectasis w ithSuppurationSuppuration
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Clinical ManifestationsClinical Manifestations
CoughCough
MalodorouspurulentsputumMalodorouspurulentsputum
SometimesbloodySometimesbloody
FeverFever
DyspneaDyspnea
Complications andComplications andCauses of DeathCauses of Death
BronchialobstructionBronchialobstruction respiratoryfailure(ventilatory)respiratoryfailure(ventilatory) ProgressivenecrosisProgressivenecrosis lungabscess lungabscess
Septicembolism
(brain
abscesses)Septic
embolism
(brain
abscesses)
orpu mona e cause yprogress ve ros sorpu mona e cause yprogress ve ros s
SecondaryamyloidosisSecondaryamyloidosis
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