Tusea, expectoratia, examenul microscopic al sputei,hemoptiziaConf Dr D Isacoff

Tusea

Tusea Reflex de aparare a tractului respiratorDeclansat cand receptorii sunt stimulati mecanic (atingere, deplasare, inflatie) si/sau chimic (gaze iritante, fum, substante chimice capsaicina, anestezice volatile)Receptorii pentru tuse: perete posterior al traheei carina punctele de bifurcatie ale bronhiilor ureche externa, esofag, organe abdominale

TuseaExpiratie exploziva care protejeaza plamanul impotriva aspiratiei si favorizeaza mobilizarea secretiilor si a altor constituienti ai cailor aeriene catre guraElement critic in auto-curatirea si al mecanismelor protectoare ale plamanAct reflex care se naste din stimularea mucoasei bronsice intre laringe si bronhiile de ordinul 2

Tusea - stimuliiParticule inhalateMucusul elaborat de epiteliul bronsicExudat inflamator in bronhii sau parenchimCorp strain (nou crescut sau aspirat)Presiune pe peretele extern al bronhiei

Tusea - ReceptoriReceptorii pentru tuse: perete posterior al traheei carina punctele de bifurcatie ale bronhiilorureche externa esofagorgane abdominale

TuseaFibrele senzitive ale nerv vag: Conduc impulsurile la centrul tusei din creierStimueaza secretia de mucus din glandele submucoase

TuseaFazele tusei:InspiratorieCompresiva (expir fortat cu glota inchisa)Expulziva (deschiderea glotei si flux de aer rapid)Expiratia reflexa (reflex expirator) indus de iritatie chimica sau mecanica a corzilor vocale sau traheei

Tusea - AnamnezaDurataCand apare: noaptea, ziua la trezire efort, expunere la praf, polen dupa mese pozitie culcata, nocturnaProductiva sau neproductiva, cantitatea si culoarea sputei

Tusea - AnamnezaAsocieri: HemoptizieFebraDispneeWheezingCuratirea gatuluiSenzatie de picurare in gat

Tusea - AnamnezaAsocieri:Durere toracicaEdem gambaOrtopnee/dispnee paroxistica nocturna

Tusea - AnamnezaAPP:Prezenta unei boli pulmonare: astm, eczema, febra de fanSinuzitaTusea convulsivabronsiectaziiBoala cardiaca, valvulopatie

Tusea - AnamnezaMedicatia: IECA, amiodarona, -blocantOcupatia: iritanti la locul de muncaAnimale/pasariFumatorUtilizare droguri recreationale

Tusea - clasificareVoluntaraInvoluntara

Acuta: 8 saptamani

ProductivaNeproductiva

Tusea acuta - CauzeInfectii virale ale CA: faringita laringita traheobronsita bronsiolitaReflux gastroesofagianAstm bronsicInhalare iritanti: fum, smog, aer extrem rece/cald

Tusea acuta - CauzeInfectii bacteriene: pneumonia sinuzita maxilara abces pulmonar Bordetella pertusisEdem pulmonarEmbolism pulmonar

Tusea acuta - CauzePneumonia de aspiratieAspiratia corp strainInflamatia laringianaOtita externa/mediePleurita, pericardita, mediastinita

Cauzele cele mai frecvente de tuse acutaInfectiile tract respirator superiorSinuzita acutaRinita alergicaAstmul bronsic

Tusea cronica - CauzeSindrom picurare postnazalRinite alergiceRinita vasomotorieSinuzita bacteriana cronicaSinuzita fungica sau alergicaRinite nealergiceAstmul bronsicReflux g-esofagianBronsiectaziileNeoplasme (endobronsice, laringe)Abces pulmonarBoli pulmonare interstAspiratia recurenta (HH, acalazia)

Tusea cronica - CauzeTusea indusa medicamentosIECA-blocanteAmiodarona

Edem pulmonar acutStenoza mitralaTbc pulmonaraTusea psihogenaOtite croniceDiverticul ZenkelAnevrism AoInflam cr a pleurei, pericard, mediastin

Tusea cronicaCauzele cele mai frecvente ale tusei cronice la pacientul imunocompetent nefumator:Astmul bronsicRefluxul gastroesofagianSindromul de picurare postnazala

Tusea cronica: cauzele cele mai frecvente

Rinite 2530%Astm/bronsita eozinofilica2025%Refluxul gastroesofagian 1520%Tusea postvirala 510%Bronsita cronica 510%Bronsiectaziile 510%Tusea indusa de IECA 510%Neexplicata 520%

Tusea cronicaAnamnezaExamen fizicExamene paraclinice90% din cazurile de tuse cronicaTusea cronica poate fi simultan produsa de mai mult decat o cauza la 19-60%

Evaluarea initiala a pacientului cu tuse: AnamnezaTusea: debut, durata, caracterul, triggers (declansatorii)Sputa (volum, caracter)Fumat, profesiaInfectia tract respirator superiorFolosirea medicamente (IECA)Astm: dispnee, wheezing, simptome nocturne, prezenta atopieiRGE: simptomele asociate cu reflux gastroesofagianRinita: picurarea postnazala, sinuzita, curatirea gatului, congestia nazalaCalitatea vietii: durere musculoscheletica toracica, incontinenta, sincopa, anxietate, tulburari de somn

Evaluarea initiala a pacientului cu tuse: Examenul clinicHippocratism digitalInspectia cavitatii nazale: polipiOrofaringe: semne ale picurarii postnazale, hipertrofie amigdalianaTorace: semnele obstructiei bronsice, raluri crepitante/subcrepitante

Evaluarea initiala a pacientului cu tuse: InvestigatiiRadiografia toracicaSpirometrie cu test bronhodilatatorDeterminare seriata a peak expiratory flowHLG completa si determinarea diferentiata a numarului de eosinofile

Tusea cronica Investigare paraclinicaRadiografia SAF: ~30% au sinuzitaCT scan sinusuri: valoare diagnostica supInvestigarea g-intestinala: monitorizarea pH esofagian pentru 24 oreCTHR toraceBronhoscopia: poate evidentia bronholitiaza, traheobronhopatia diskinezia laringiana, corp strain

Tusea cronicaInvestigare paraclinicaEvaluarea inflamatiei bronsice:Sputa indusaMasurarea NO in aer expiratProvocarea tusei prin inhalare de:acid citric capsaicina acid tartaric nebulizare apa distilata

Tuse >3 saptamaniAnamneza, examen clinicDiagnosticul nu este evidentRx toraceSpirometrie Normal Test brconstrictieEvaluare pt RGEDiagnostic incertInfectie recenta CASDispnee paroxistica nocturnaMedicamente (IECA)Evaluare GI: endoscopie, Rx EGD, deglutitieEvaluare cardiologica: Ekg, Ecocardiaca, Test efort, Cateterism cardiacEvaluare pulmonara: CT torace, bronhoscopie

Tusea - ComplicatiiRespiratoriiPneumotoraxEmfizem subcutanatPneumomediastinLezare laringianaCardiovasculareTulburari de ritmPierderea constienteiHemoragie subconjunctivala

Tusea - ComplicatiiSNCSincopaCefaleeEmbolism aeric cerebralDiverseIncontinenta urinaraPetesiipurpuraMusculoscheletice Dureri intercostaleRuptura m drept abdominalCPK in serProlaps disc i-vertebral cervicalGastrointestinalePerforare esofag

Tusea varianta de astmSubgrup astmatici cu tuse cronica, care este rezultatul sensibilitatii excesive a reflex tuseTuse uscata sau minim productiva, apare nocturn, dupa efort sau expunere profesionala sau la alergeni

Tusea varianta de astm DiferentiereaDemonstrarea obstructiei bronsice variabile: PEF SpirometrieDemonstrarea HRB prin test de provocareNumar eozinofileTeste cutanateAmeliorarea sub tratament

Tusea indusa de IECA8% din utilizatorii de IECAMai frecventa la femeiMecanism: BK si Pg in caile aerieneSe remite prompt la intreruperea IECA! Persistenta poate sugera astmul bronsic

Tusea din riniteRinita se asociaza frecvent cu sinuzita si picurarea posterioaraCauze: alergia si infectiaTusea apare prin stimularea mecanica prin picurarea postnazala si extensia inflamatiei locale la faringe si laringeCongestie nazala, rinoree, durere faciala, nevoie frecventa de curatare a gatului

10.000 microorganisme inhalate zilnic 500-5.000 germeni/m in mediul exterior15.000-20.000L aer inhalat zilnic si ~300 milioane L aer inhalat in timpul vietiiMucoasa bronsica trebuie sa dispuna de mecanisme de aparare pentru a preveni colonizarea si penetrarea bacteriana

Apararea mecanicaPerii nazali particule cu diam >10mFlux aeric rapid si modificarile rapide de directie prin nas Mucoasa ciliata de pe sept si cornete nazale directioneaza secretiile catre faringele posterior

Mecanismele de aparare ale mucoasei bronsiceSecretia de mucusClearance-ul mucociliarApararea celularaApararea imunologica

Bariera fizicaJonctiuni cel epitEscalador mucociliarIndepartarea agent agresorFagocitoza leucocitaraFagocitoza CEpit/CEApoptoza celulelor tintaRaspunsuri reglate de mediatoriActivarea CEActivare&Recrutare leucociteActivarea celule epitelialeActivarea cascadei coagulariiActivarea raspunsurilor imuneProliferarea si regenerarea celularaRevascularizatiaRemodelarea tisularaDereglarea cascadei inflamtieiInjurie tisulara si boalaRecuperare Apararea pulmonara

Raspuns imediatBariera anatomica Monostrat epitelial si jonctiunile intercelulare Tusea Transport mucociliar PrecoceImunitatea naturala Lichid epitelial & compusii antimicrobieni Macrofage pulmonare si alveolare Activarea mastocite Activarea cel epiteliale si endoteliale Activarea complementRaspuns tardivImunitatea adaptativa Recrutarea si activarea neutrofilelor Recrutarea si activarea limfocitelor

*Raspunsul tractului respirator la fumul de tutunReproduced from The Lancet, Vol 364, Barnes PJ & Hansel TT, "Prospects for new drugs for chronic obstructive pulmonary disease", pp985-96. Copyright 2004, with permission from Elsevier.Fuma tigaraCelule epitelialeCelule TcCD8+EmfizemProteazeHipersecretie de mucusMacrofag/Celula dendriticaNeutrofilMonocitFibroblastBronsiolita obstructivaFibrozaThis slide illustrates that COPD is a complex disease with many inflammatory pathways that initiate and potentiate the disease process.CD8+, Cigarette, Emphysema, Epithelial, Macrophage, Monocyte, Mucus, Neutrophil

*Macrofagele alveolare in BPOCBarnes. J COPD. 2004;1:59-70. Copyright 2004 from "Alveolar Macrophages as Orchestrators of COPD" by Barnes. Reproduced by permission of Taylor & Francis Group, LLC., www.taylorandfrancis.comThis slide shows how macrophages play a pivotal role in COPD and secrete many inflammatory proteins that orchestrate the inflammatory process in COPD. HDAC, IL-8, Macrophage, MMP, NO, ROS, Steroid Resistance

*Factori chemotactici in BPOCBarnes. Curr Opin Pharmacol. 2004;4:263-272.Hill et al. Am J Respir Crit Care Med. 1999;160: 893-898.Montuschi et al. Thorax. 2003;58:585-588.MCP-1GRO-Fragmente elastina

LTB4IL-8GRO-Fragmente elastinaIP-10MigI-TACNeutrofileMonociteCelule TOnce activated, alveolar macrophages and epithelial cells release chemotactic factors (chemokines) that result in neutrophil recruitment. CXC3 chemokines, Elastin, IL-8, LTB4, Macrophage, MCP-1, Neutrophil, T cell

*Elastinele in dezvoltarea emfizemuluiReproduced with permission of Nature Med, from Antielastin autoimmunity in tobacco smoking-induced emphysema, Lee et al, Vol 13, Copyright 2007; permission conveyed through Copyright Clearance Center, Inc.Proposed immunopathologic model of autoimmune emphysema, including innate and adaptive immune components.B cell, CXCR3, Elastin, Emphysema, Macrophage, Neutrophil Elastase

*Epiteliul bronsic si ROS&NeutrofileleReproduced from Clin Applied Immunol Rev, Vol 5, Daheshia M, Pathogenesis of chronic obstructive pulmonary disease (COPD)", pp339-351.Copyright 2005, with permission from Elsevier.This slide summarises the molecular events and cellular involvement during the pathogenesis of COPD.CD8+, Epithelium, Interleukin, Macrophage, Mucus, Neutrophil, TNF-

Mediatori chemotactici Defensine Chemokine Leucotriene

Mediatori inflamatori Citokine Chemokine Leucotriene ROS&RNSLichidul bronsic Peptide/compusi antimicrobieniBariera fizica Cili&escalador mucociliar

Receptori membranari Molecule adeziunii Receptori proteaze Receptori Toll-like

Substante antimicrobiene Defensine Fosfolipaza A2 SP-A, SP-B Peptide cationice ROS&RNSMecanismele apararii celulare sistem de aparare foarte eficient

Originea mucusului bronsiccelulele caliciformecelulele seroase epitelialecelulele secretorii din submucoasacelulele ciliateDeci, mucusul bronsic este o mixtura heterogena de diferite secretii.Sputa expectorata este un amestec de saliva cu mucus bronsic

Functiile mucusului bronsic1. Mecanisme protectoareUmidificarea aerului inspiritIzolarea poluantilor atmosfericiProtectie antibacteriana/antiviralaMediu adecvat pentru actiunea ciliaraReduce pierderea de lichidUmezeste suprafata CA

Functiile mucusului bronsic2. Functie de barieraInglobeaza microorganismeDizolva gazele toxiceSita selectiva pentru macromoleculeSuprafata extracelulara pentru actiunea IgSuprafata extracelulara pentru actiunea enzimelor

Functiile mucusului bronsic3. Functie de transport reprezinta, impreuna cu cilii, invelisul sau teaca pentru depunerea materialelor captate

Mucusul bronsic este secretat in principal de catre glandele submucoase traheobronsice si in grad mai mic de celulele caliciforme de pe epiteliul de suprafata.Volumul secretiilor respiratorii:Persoanele sanatoase: 0,1-0,7ml/Kg/24 h ~ 8- 50 ml/zi, sau 10-100 ml, care in mod normal este inghitit

Compozitia mucusului bronsic normalApa 95%Macromolecule 4% glicoproteine ale mucusului 25-50% lipide 20-30% proteine 10-20% ioni (Na, K, Cl, P, Ca) si constituienti dializabili Structura mucusul traheobronsic: aspectul de gel. Structura de gel a mucusului se datoreaza mixturii apei cu glicoproteinele mucusului sau mucine

Constituientii macromoleculari ai mucusului Macromoleculele OrigineaGlicoproteine mucus: MucineFucomucine (neutre)celulele cupuformeSialomucine (acide)glandele submucoaseSulfomucine (acide)

Constituientii macromoleculari ai mucusuluiProteine produse localLizozimmacrofage, leucocite, celule seroase(glandele submucoase)Lactoferina celulele seroase (glande submucoase)IgA, IgG, IgM, IgEplasmociteC3 macrofage2 macroglobulinafibroblaste1-antitripsinamacrofagepiesa secretorie liberacelulele mucoase (glandele submucoase)s-IgAplasmocite si cellule mucoase

Constituientii macromoleculari ai mucusuluiProteine provenite prin difuzie pasiva din sangealbuminaproalbuminaceruloplasmina haptoglobinatransferina1-glicoproteina acida1-antichimotripsinafibrinogenantitrombina III

Constituientii macromoleculari ai mucusuluiLipide produse localglicolipidefosfolipidecelule alveolare tip IIlipide neutre(surfactantul alveolar)

Proprietatile fizice ale mucusuluiMucusul bronsic poseda 2 caracteristici fizice importante: viscozitateelasticitateCapacitatea mucusului traheobronsic de a fi mobilizat de-a lungul cailor aeriene depinde in principal de viscozitatea si elasticitatea lui

Afinitatea bacteriana pentru mucusul bronsicCarbohidratii sunt principalii receptori pentru adeziunea bacteriana, ceea ce inseamna ca mucusul este bogat in potentiali receptori pentru bacterii. Principalii patogeni respiratori care se leaga de mucoasa respiratorie:Pneumococul H influenzae S aureus

Afinitatea bacteriana pentru mucusul bronsicUnii patogeni respiratori elaboreaza si elibereaza produsi care stimuleaza secretia de mai multa mucina si/sau interfera cu transportul mucociliar prin aglutinarea celulelor sau prin dezorganizarea batailor ciliare sau chiar lezarea epiteliului. Astfel, bacteriile pot contribui la dezvoltarea unui mediu favorabil cresterii si persistentei lor in caile aerine infectate.

Cilii, clearance-ul mucociliar si interactiunea bacteriana Fiecare celula traheobronsica ciliata este acoperita la marginea apicala de catre 200-300 cili care functioneaza prin miscarea mucusului si lichidelor peste suprafata respiratorie.

Caracteristicile cililor mucoasei respiratoriiParametrii DimensiuniLungime5-8 mDiametru0,15-03 mDistanta dintre cili0,3-0,4 m Densitatea cililor6-10/mNumarul de cili per celula200-400MetacronismantiplecticLungimea undei methacronale20-40 mFrecventa batailor10-30 Hz (600-1000 miscari/min) Velocitatea medie a mucusului 5-10 mm/minTrahee 5-20 mm/minBronchiole terminale100-600 m/min

Agonistii secretiei de mucinaNeuromediatoriAgonisti adrenergiciAgonisti colinergiciSubstanta PVIPMediatori inflamatoriPg A2, D2, F2Leucotriene: C4, D4, E4ROSHistamina mastocitProt cationica eozinofilPAFATP

Agonistii secretiei de mucinaProdusi bacterieniElastaza Ps aeruginosaRamnolipide Ps Alginat Ps aeruginosaProteazeChymaza mastociteElastaza neutrofileCathepsina G neutrofileProteaza 3 neutrofile

Interactiunea bacteriilor cu cilii si clearance-ul mucociliar Factorii bacterieni perturba motilitatea cililorPseudomonas aeruginosa produce: pyocyanina 1-hidroxi-phenazinarhamnolipidH influenzae produce glicopeptide cu greutate moleculara micaS pneumoniae produce pneumolisina

CA: Escaladorul mucociliarTusea si clearance mucociliar = principalele mijloace de aparare mecanicaCresc frecv batailor ciliare: TNF-, IFN-, IL-6Functia mucociliara este afectata de: oxidanti elastaze fumat

Expectoratia Mecanism al organism prin care indeparteaza secretiile acumulate neindepartate prin clearance-ul mucociliarCuloareCantitateConsistentaMiros

Expectoratie- tuse productivaPoate fi exteriorizata prin: o singura tuse tuse paroxisticaPoate fi indusa voluntarEste raspuns reflex la stimularea mucoasei bronsiceRezulta din inflamatia acuta sau cronica (infiltrat inflamator, edem, hipersecretie)

ExpectoratiaSindrom de imunodeficienta dobanditaInhalarea de substante antigenice sau iritante corpi straini

ExpectoratiaFumatul = cauza cea mai frecventa de expectoratie cronica; Fumatorii minimalizeaza tusea cronica productiva pana cand apar: dispnee hemoptizie durerea toracica scaderea ponderala infectii respiratorii recurente

Expectoratia Sputa mucopurulenta: pneumonie bacteriana, bronsita; ! Neutrofile sau eozinofile in numar mare aspect purulentSputa apoasa: Mycoplasma, adenovirozeSputa ruginie sugereaza afectarea alveolara; pneumonia cu pneumococSputa jeleu de coacaze = pn Klebsiella

SputaSputa neagra: mineri in carbuneSputa maronie: fumatoriSputa stratificata: bronsiectazii, abces pulmonar, bronsita cu bronhoreeSputa mucoida >1L/zi: C. cel. alveolareBronhoree mucoida: bronsita cr (ocazional)Sputa urat mirositoare: infectie cu anaerobi (abces pulmonar, bronsiectazii)

SputaCilindrii fibrinosi: bronsita plasticaSputa perlata sau cu structuri vermiculare alcatuite din cilindrii bronsiolari: astmDopuri de culoare bruna: aspergiloza bronhopulmonara alergicaSputa cu pietris: mici calculi = bronholitiaza (Ca din ggl granulomatosi erodeaza perete bronsic

Sputa Colectare dimineata, a jeun, dupa clatirea guriiSputa indusa dupa inhalarea de aerosoli de NaCl 15% + glicerina 10% timp de 10 min sau pana expectoreazaAspirat trahealLavaj bronhoalveolar

Prelucrare ? Sputa provine din tract respiratorColoratie Gram a unui fragment purulentEsantion acceptat: >10 celule epiteliale/camp microscopic >25 celule epiteliale si >25 neutrofile/campLegionella: culturi + test rapid cu Ac fluorescent sau Ag Legionella in urinaBK: 3 esantioane in 3 zile separate

Examenul bacteriologic al sputeiFrotiu direct colorat GramColoratie Ziehl NielsenCulturi + antibiograma

Sputa: coloratie GramCelule scuamoase epitelialeLeucocite polimorfonucleare si macrofage alveolare

Frotiu sputa colorata GramL: 25L: 10-25; CE: > 25L: >25; CE:

Klebsiella pneumoniaeAspect macroscopic: jeleu de coacazeColoratie Gram: bacili Gram negativ

Sputa Coloratie GramColoratie Gram: neutrofile, detritus, diplococi Gram pozitiv

Sputa Coloratie GramPneumococi Haemophilus influenzaeStaphylococcus aureus

Sputa coloratie Gram Neutrofile, detritus amorf si bacili Gram pozitiv filamentosi, cu aspect de margele, ramificati (Nocardia)

Sputa- coloratie GramNeutrofile si diplococi Gram negativ intracelulari Neisseria meningitidis

Sputa coloratie GramAspectul in diplococi (Moraxella catarrhalis) poate preta la confuzie cu Neisseria sp

Sputa coloratie GramBacili Gram negativ Ps aeruginosa

Sputa coloratie GramBacili Gram negativ (E coli) ! Pseudomonas

Coloratie GramS aureus (coci Gram pozitiv in perechi, lanturi scurte, ciorchini

Coloratie Ziehl-NielsenSputa, coloratie Ziehl-Nielsen: bacili acido-alcoolo pozitivi (Mycobacterium tuberculosis)

Coloratie Ziehl-Nielsen

Sputa indusa

Sputa indusa astmaticSpirala Curschmann

Sputa indusa astmatic: cristale Charcot-Leyden

Sputa indusa: corpi Creola

Sputa indusa la fumatorCelula giganta multinucleata

Sputa indusa:Macrofag cu coada roz

Examenul citologic al sputei

Coloratie Papanicolau

Aspirat bronsic: celule carcinom scuamos

Aspirat bronsic: celule carcinom scuamos

Sputa indusa: carcinom scuamos invaziv

Aspirat bronsic: adenocarcinom

Aspirat bronsic: carcinom bronhoalveolarNucleoli proeminenti si conexiuni intercitoplasmatice

Brasaj bronsicAspirat gglCelule gigante multinucleate si limfociteGranulom necazeosSarcoidoza

Sputa indusa: corp feruginos

LBA priza cocainaMacrofage cu material pigmentat abundent in citoplasma

Brasaj bronsic: Strongyloides

Sputa indusa: Paragonimus (ou)

LBA: pneumonie lipoidicaCelule mari vacuolate cu nuclei hipercromi si nucleoli proeminenti. Poate determina confuzii cu adenocarcinom

LBA: AspergillusConidiospor Filamente mari de Aspergillus ramificate in unghi ascutit

Aspirat pulmonar pe ac fin: Coccidioidomices

Aspirat pulmonar pe ac fin: Histoplasma in macrofag

Bronholiti

LBA: sindrom GoodpastureSange proaspat si macrofage incarcate cu sange

Hemoptizia Anamneza: boala pulmonara in APPEvaluarea volum sanguin, daca este sange proaspat sau vechi (alterat)Evaluare in timp: intermitenta, constantaSangele provine din CA sau: nas, gura, GIPrezenta infectiei? Neoplazie subiacenta

Hemoptizia Ex clinicNormalSemne ale:bronsiectazii cancer pulmonar colaps circulator

Hemoptizia Diagnostic diferentialNeoplasmBronsiectaziiTbc/infectieEmbolism pulmonar

HemoptiziaCauze frecventeTumori bronsice:BenignaCarcinoidMaligna Bronsiectazii Tbc activaPneumoniaBoala TE pulmonaraVasculiteWegenerLESSd GoodpastureTratament cu anticoagulante

HemoptiziaCauze rareAbces pulmonarMycetomInfectii fungiceInfectii parazitareEmbolism grasosMalformatii A-VSindr Rendu-OslerHTPu severaStenoza mitralaCardiopatii congAnevrism aortaAspergilozaCoagulopatiiEndometriozaHemosideroza pulmIatrogena

Hemoptizia: AnamnezaFumat: carcinom bronhogenNeoplasm diagn anterior: Metastaze bronsiceBoala pulmonara sau cardiaca sau vasculara pulmonara sau boala sistemicaTraumatism sau procedura toracica recenta: injurie toracica/pulmonara iatrogenaFactori de risc pt aspiratie: abces pulmonar, aspiratie corp strain

Hemoptizia: SimptomeSputa purulenta: Bronsiectazii, bronsita, pneumonie, abces pulmonarDurere pleuretica: Pneumonie, EPDispnee paroxistica nocturna, ortopnee: IVS, stenoza mitralaFebra: Pneumonie, abces pulmonarScadere ponderala: carcinom bronhogen, alte neoplazii, tuberculoza, abces pulmonar

Hemoptizia: SemneSuflu tubar, egofonie: PneumoniaDiminuare localizata a zg respir, wheezing localizat: Carcinom bronhogenic, bronholitiaza, corp strainSubcrepitante mari, buloase, rhonchusuri: Bronsiectazia, bronsitaFrecatura pleurala: Pneumonie, EPGalop S3: IVSUruitura diastolica: stenoza mitrala

HemoptiziaInvestigatiiPrima linie:HLG grup sanguin teste coagulare examen citologic sputaRgrafie torace tumora bronsiectazii sindrom de condensare malformatii arterio-venoase

Semne radiograficeAfectiuniNoduli sau tumora C bronsic sau alt neoplasm, abces pulmonar, granulomatoza Wegener, infectie fungicaAtelectazie C bronsic sau alt neo endobronsic, bronholitiaza, corp strainAdenopatie hilara/mediast C bronsic sau alt neoplasm, infectie mycobacteriana sau fungica, sarcoidozaBronhii periferice dilatateBronsiectaziaCondensare alveolara Pneumonie, hemoragie alveolara, contuzie pulmonaraOpacitati reticulonodulareSarcoidoza, limfangita carcinomatoasaCaverne/cavitatiInfectie mycobacteriana sau fungica, mycetoma, abces pulmonar, C bronsicCalcificare hilara/mediastinalaInfectie veche mycobacteriana sau fungica, bronholitiaza

HemoptiziaInvestigatiiCT toraceBronhoscopie vizualizeaza CA localizeaza sediul sangerarii are valoare terapeutica obtine material pentru ex histopatologic (biopsie bronsica, transbronsica)

HemoptiziaInvestigatiiLinia a II-a:CTHR pentru excluderea EPAngiografia bronsicaEmbolizare arteriala bronsicaEx ORLEx ecocardiografic

HemoptiziaDiferentierePseudohemoptizia = sange din tract digestiv superiorLeziuni CASEpistaxisGingivoragiiCarcinom laringianTraumatism CA

Anevrism Rasmussen

Malformatie AV pulmonara (tumora plexiforma de vase dilatate )

Fistula AV LIS

Malformatie AV

Anevrism aorta toracica

Carcinoid bronsic

Sindrom vena cava superioara

Tumora endobronsica

Tumora maligna tiroidiana

Bronholitiaza

Carcinom bronsic cu celule scuamoase

Biopsie pulmonara transtoracicaMacrofage degenerate in numar mare si celule alveolare care contin hematii ingerate

Bronsiectazii post-tuberculoza pulmonara

Host defense. The pulmonary host defense system is composed of multiple components, including physical barriers such as the nose and mucous layer that lines the airways. Mechanisms also exist to remove offending microbial pathogens or noxious particles, either directly by phagocytosis or endocytosis or indirectly by mediator-regulated responses. Activation of the immune and inflammatory responses will usually facilitate resolution of the injury and recovery of the host. However, if these immune and inflammatory responses are excessive orunregulated, tissue injury and disease ensue.Speaker NotesThis slide illustrates that COPD is a complex disease with many inflammatory pathways that initiate and potentiate the disease process. Neutrophils, macrophages and CD8+ T-lymphocytes are the key inflammatory cell types involved in COPD.Additional InformationAirway inflammation in COPD is characterized by a neutrophilic inflammation with increased numbers of macrophages and CD8+ T-lymphocytes. These cells release the reactive oxygen species (ROS), chemokines (e.g. interleukin [IL]-8), cytokines (e.g. tumor necrosis factor [TNF]-) and proteases (e.g. neutrophil elastase and matrix metalloproteinase) that are instrumental in producing a chronic inflammatory state. The ongoing inflammatory process leads to enlargement of the alveolar spaces, fibrosis, destruction of the lung parenchyma, loss of elasticity and small airways obstruction (obstructive bronchiolitis). Mucus hypersecretion is a prominent features of COPD. In contrast to asthma, airway hyperresponsiveness is not a routinely present feature of COPD. ReferencesBarnes PJ. Mechanisms in COPD. Differences from asthma. Chest 2000; 117 (Suppl 2): 10S14S.Barnes PJ. COPD: is there light at the end of the tunnel? Curr Opin Pharmacol 2004; 4: 263272.Barnes PJ, Hansel TT. Prospects for new drugs for chronic obstructive pulmonary disease. Lancet 2004; 364: 985996.Speaker NotesMacrophages play a pivotal role in COPD and secrete many inflammatory proteins that orchestrate the inflammatory process in COPD.Their numbers are markedly increased in the lung and alveolar space of COPD patients.Neutrophils, monocytes and CD8+ cells are all attracted to the lung by mediators released by the macrophages.The release of elastolytic enzymes causes elastolysis and contributes to the development of emphysema.Macrophages also generate ROS and nitric oxide (NO), which together form peroxynitrite and may contribute to steroid resistance.

Additional InformationNeutrophils may be attracted by IL-8, growth related oncogene- (GRO-) and LTB4; monocytes by GRO- and macrophage chemotactic protein-1 (MCP-1); and CD8+ lymphocytes by interferon (IFN)- inducible protein (IP-10), monokine-induced by IFN- (Mig) and IFN-inducible T-cell -chemoattractant (I-TAC). Elastolytic enzymes include matrix metalloproteinases (MMP) and cathepsins.

ReferenceBarnes PJ. Alveolar macrophages as orchestrators of COPD. J COPD 2004; 1: 5970.Speaker NotesOnce activated, alveolar macrophages and epithelial cells release chemotactic factors (chemokines) that result in neutrophil recruitment. The major chemotactic factors are leukotriene B4 (LTB4) and IL-8, though other CXC (cysteine-X-cysteine) chemokines may be involved.GRO- and MCP-1 are elevated in sputum and BAL, and are associated with recruitment of monocytes.CXC3 chemokines (IP-10, Mig, I-TAC) are elevated in COPD and recruit CD8+ cells.While LTB4 and IL-8 are mainly derived from macrophages, epithelial cells and neutrophils, they may also be released from activated neutrophils, resulting in further neutrophil activation and recruitment.

ReferencesBarnes PJ. COPD: is there light at the end of the tunnel? Curr Opin Pharmacol 2004; 4: 263272.Hill AT, Bayley D, Stockley RA. The interrelationship of sputum inflammatory markers in patients with chronic bronchitis. Am J Respir Crit Care Med 1999; 160: 893898.Montuschi P, Kharitonov SA, Ciabattoni G, Barnes PJ. Exhaled leukotrienes and prostaglandins in COPD. Thorax 2003; 58: 585588.Speaker NotesProposed immunopathologic model of autoimmune emphysema, including innate and adaptive immune components. Exposure to cigarette smoke induces secretion of proteolytic enzymes from cells of the innate immune system, in particular neutrophils (elastase) and macrophages (MMP-9, MMP-12) that liberate elastin fragments in the lung. Prolonged exposure to cigarette smoke results in the accumulation of elastin fragments, which are presented by antigen-presenting cells (APCs) to T cells through MHC class II molecules that can in turn activate elastin-specific B cells. Lack of lung TR cells results in clonal expansion of elastin-specific TH1 cells, and their release of cytokines and chemokines such, as IFN-, IP-10 (CXCL10) and MIG (CXCL9). Activation of CXCR3, through its ligands CXCL9 and CXCL10, enhances secretion of MMP-12, which in turn inhibits -1antitrypsin, leaving neutrophil elastase, a potent elastolytic enzyme, unopposed. The synergistic activation of several proteinases with elastolytic potential, orchestrated by autoreactive TH1 cells, ultimately leads to massive elastolysis and emphysema even long after exposure to tobacco smoke ceases.

ReferenceLee SH, Goswami S, Grudo A, et al. Antielastin autoimmunity in tobacco smoking-induced emphysema. Nat Med. 2007;13:567-569. Speaker NotesThis slide summarises the molecular events and cellular involvements during the pathogenesis of COPD. Exposure of the lung to toxins could activate alveolar macrophages and the airway epithelium to generate chemotactic factors.Once released, these factors induce a cascade of events leading to infiltration of the lung with hematopoietic cells that directly or, in association with aerosol, stimulate the release of several destructive factors that damage the pulmonary architecture. Additionally, infiltrating cells could themselves be a new source of chemotactic factors, which could sustain the inflammatory reactions in the lung, leading to a chronic and progressive disease.

ReferenceDaheshia M. Pathogenesis of chronic obstructive pulmonary disease. Clin Applied Immunol Rev. 2005;5:339-351.

Epithelial cell defense mechanisms. The pulmonary epithelial monolayer functions as a highly effective defense system. The different mechanisms are illustrated, including the airway surface liquid that contains potent antimicrobial compounds, the mucous layer,junctions between the epithelial cells, and surface receptors expressed by the epithelial cells. ROS, Reactive oxygen species; RNS, reactive nitrogen species; ICAM, intracellular adhesion molecule; SP-A, surfactant associated protein A; SP-D, surfactant associated protein D.Gram-stained appearance of typical cells on sputum smears. (original magnification, 630.) A, Squamous epithelial cells. B, Alveolar macrophage and three polymorphonuclear leukocytes Gram-stained smears of representative sputum specimens. (original magnification, 100.) A, Leukocytes 25. B, Leukocytes 10 to 25, epithelial cells >25. C, Leukocytes >25, epithelial cells