dkhi - chronic obstructive airway disease

8/9/2019 DKHI - Chronic Obstructive Airway Disease

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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

dkhi - chronic obstructive airway disease

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