The respiratory system Markéta Hermanová Congenital anomalies nAgenesis or hypoplasia (both lungs, one lung, single lobes); -hypoplasia most often secondary: congenital diaphragmatic hernia, renal cystic disease, renal agenesis, anencephaly, prolonged rupture of fetal membranes n nTracheal or bronchial anomalies -atresia -stenosis -tracheooesophageal fistula n nCongenital lobar emphysema n(overdistension of a lobe due to intermittent bronchial obstruction….related to abnormal bronchial cartilage, allowing inspiration, restricting expiration) n nBronchogenic/foregut cysts -hilus or middle mediastinum -bronchogenic – most common -esophageal or enteric n Pulmonary sequestration ………no normal connection to the airway system Congenital pulmonary airway malformation (CPAM) (congenital cystic adenomatoid malformation (CCAM)). Good prognosis……………………………………………poor prognosis. Atelectasis; collapse nAtelectasis -primary; neonatal; immature neonates, lack of surfactant n nCollapse (secondary, previously inflated lungs) = acquired atelectasis 1.Obstruction (resorption of the air after the blockage) 2.Compression (hydrothorax, pneumothorax, pleural exsudate) 3.Contraction atelectasis (fibrotic changes prevent full expansion) Immaturity: - hyaline mebrane disease (HMD) or idiopathic distress syndrome - bronchopulmonary dysplasia nComplication of prematurity (less than 36 weeks gestation) n nDue to deficiency of pulmonary surfactant n nTachypnoe, dyspnoe, expiratory grunting, cyanosis n nDiffuse alveolar damage with hyaline mebranes n nBronchopulmonary dysplasia – lung organisation after HMD (+oxygen toxicity); interstitial and peribronchial fibrosis Pulmonary edema (congestion) nHemodynamic 1.Increased pulmonary venous pressure – venostatic edema (left sided heart failure, volume overload, pulmonary vein obstruction) 2.Decreased oncotic pressure (hypoalbuminemia, nephrotic syndrome, liver disease, protein loosing enteropathies) 3.Lymphatic obstruction n nDue to microvascular injury (alveolar injury; leakage of fluids and proteins into interstitium and later into alveoli) 1.Infections (pneumonia, septicemia), shock, trauma 2.Inhalation of toxic gases 3.Liquid aspiration 4.Drugs, chemicals 5.Radiation n nUndetermined origin 1.High altitude 2.CNS trauma Pulmonary edema 9x40 9x400 Adult respiratory distress syndrome (ARDS)/acute lung injury (ALI) – diffuse alveolar damage (DAD) – shock lung – acute alveolar injury. Acute respiratory failure after a systemic or pulmonary insult (direct or indirect lung injury); short history of dyspnoe, tachypnoe and respiratory distress/failure. nShock (haemorrhagic, cardiogenic, septic, anaphylactic, endotoxic,…) nDiffuse pulmonary infections, sepsis nGastric aspiration nChemical injury (heroin, methadon, barbiturate overdose, acetylsalicylic acid) nTrauma (direct pulmonary or multisystem trauma) nHaematologic conditions (DIK, multiple trasfusions) nPancreatitis nUremia nInhaled irritants (oxygen toxicity, smoke, toxic gases) nHypersenzitivity reaction (organic solvents, drugs – anticancer treatment) Morphology of ARDS (DAD) nMacroscopy (congestion, redness of the lungs, hypoinflation) n nMicroscopy 1.Exsudative stage: edema, interstitial and intraalveolar, inflammation, fibrin deposition, hyaline membranes 2.Organizing stage: proliferation of type II cells and regeneration of epithelial lining, organisation of fibrin exsudate resulting in intraalveolar fibrosis, interstitial fibrosis due to proliferation of interstitial cells and deposition of collagen 3. ARDS – hyaline membranes 8x40 8x200x2 nObstructive pulmonary diseases n(increase in resistence to airflow due to partial or complete obstruction at any level) nChronic bronchitis nEmphysema nAsthma nBronchiectasia n nChronic bronchitis + emphysema = chronic obstructive pulmonary disease (COPD) nRestrictive pulmonary diseases n(reduced expansion of lung parenchyma with decreased total lung capacity) nChest wall disorders in presence of normal lungs (kyphoscoliosis, pleural diseases, severe obesity, neuromuscular disorders such as poliomyelitis) nAcute or chronic interstitial and infiltrative diseases Emphysema nAbnormal permanent enlargement of the airspaces distal to terminal bronchiole, accompanied by the destruction of their wall and without obvious fibrosis; protease-antiprotease theory: inbalance between proteases and anti-proteases in the lung (genetics, smoking) + oxidant-antioxidant imbalance (reacitve oxygen species in tabacco smoke). n nCentrilobular/centriacinar (predominantly in heavy smokers, associated with chronic bronchitis) nPanlobular/panacinar (alfa-1-antitrypsin deficiency) nParaseptal, distal acinar (adjacent to areas of fibrosis, scarring, atelectasis; spontaneous pneumothorax of young adults; upper half of the lungs) nIrregular (associated with scarring) n nOthers: compensatory (hyperinflation) emphysema, bullous emphysema, interstitial emphysema (arteficial ventilation, rupture of an emphysematous bulla) emfyzém1 Emphysema lung13 10x20x2 Chronic bronchitis nSmoking!!!! nProgression to chronic obstructive airway disease nIncresing breathlessness, hypoxia, respiratory failure (type I hypocapnic, type II hypercapnic) → pulmonary hypertension, cor pulmonale and heart failure nAtypical metaplasia and dysplasia of respiratory epithelium – cancerogenesis n nClinical deffinition: cough with sputum production for at least 3 months in two consecutive years nChronic irritation, infection, congestion of the lungs – venostasis, allergy, mucoviscidosis,… Asthma bronchiale asma -Chronic inflammatory disorder of the airways; reversible small airways obstruction characterised by bronchospasm, inflammation and oedema. Paroxysmal episodes of wheezing, breathlessness, chest tightness, cough, at night/in the morning -Overdistended lungs, mucous plugs in bronchi, mucous gland and smooth muscle hypertrophy astma Asthma bronchiale nExtrinsic, atopic n (IgE-mediated external allergens) n nIntrinsic, non-atopic, idiopathic n (secondary to infection?) n nAspirin – induced n (decreased PGs or increased LT leading to airway hyperreactivity) n nAllergic bronchopulmonary aspergillosis n (inhalation of spores, immediate type I and delayed type III hypersensitivity reaction) n nOccupational n (thought to be a combination of type I and type III hypersensitivity) n n(Exercise – induced) n Bronchiectasis: permanent dilatation of bronchi and bronchioles image00110 kopie -Results from pulmonary inflammation and scarring due to infection, bronchial obstruction or lung fibrosis (e.g. after radiotherapy) - -Secondary inflammation lead to further destruction of airways - -Chronic cough with dyspnoe and production of copious amount of foul-smelling sputum -Complications: pneumonia, abscess (also metastatic (e.g. in brain), amyloid, pulmonary fibrosis, cor pulmonale - -In congenital and hereditary conditions, in chronic infections, after radiotherapy in lung and breast cancer, distal to bronchial obstruction, immunodeficiency, post-transplantation, in SLE, RA Bronchiectasis: permanent dilatation of bronchi and bronchioles caused by destruction of the muscle and elastic tissue. Etiopatogenesis, predisposing conditions: nCongenital and hereditary conditions n (mucoviscidosis, intralobar sequestration, immunodeficicency status, primary cilliary diskenesis,)) n nPostinfectious conditions n (necrotising infections bacterial (BK, SA, HI, PA), viral (HIV, influenza, adenovirus), fungal (Aspergillus)) n nBronchial obstruction n (tumors, foreign bodies,…) n nOthers n (rheumatoid arthritis, lupus erythematodes, IBD, post-transplantation) n Chronic interstitial disease/chronic interstitial lung disease (ILD) (restrictive pulmonary diseases) nFibrosing -Idiopathic pulmonary fibrosis (usual interstitial pneumonia) -Cryptogenic organizing pneumonia -Connective tissue disorders related ILD -Pneumoconiosis -Drug reactions -Radiation pneumonitis nGranulomatous -Sarcoidosis -Hypersenzitivity pneumonitis/extrinsic allergic alveolitis nEosinophilic pnemonia nSmoking-related -Desquamative interstitial pneumonia -Respiratory bronchiolitis-associated interstitial lung disease nOther -Pulmonary alveolar proteinosis n Idiopathic pulmonary fibrosis (usual interstitial pneumonia; cryptogenic fibrosing alveolitis) nHamman-Rich syndrome: previously: rapidly progressive type of IPF; now: acute lung injury, acute interstitial pneumonia n nPathogenesis: repeated cycles of acute lung injury (alveolitis) by some unidentified agent (inhaled agents, dusts, blood toxins, unknown Ag) followed by fibroblastic proliferation, widespread fibrosis and loss of lung function (end-stage lung, honeycomb lung) n nModification of inflammatory response (TH2 type) - genetic and enviromental factors n nClinical course: gradually increasing dyspnoe, dry cough, hypoxemia, cyanosis, clubbing; progression unpredictable n nTreatment: steroids, cyclophosphamide, azathioprine; lung transplantation Morphology of IPF nPleural surfaces cobblestoned due to the retraction of scars along interlobular septa n nFibrosis predominantly in the subpleural regions and along interlobular septa n nMicroscopically: patchy interstitial fibrosis n nDense interstitial fibrosis, cystic spaces lined by hyperplastic type II pneumocytes or bronchiolar epithelium (honeycomb fibrosis) n nMild to moderate inflammation (lymphocytes, plasma cells, eosinophils, neutrophils, mast cells) in fibrotis areas n nSquamous metaplasia, smooth muscle hyperplasia n nSecondary pulmonary hypertensive changes (intimal fibrosis, medial thickening of pulmonary arteries) Idiopathic pulmonary fibrosis plíce honeycomb 40x Cryptogenic organizing pneumonia (COP) = bronchiolitis obliterans organizing pneumonia (etiology unknown) nCough, dyspnea, subpleural or peribronchial patchy ares of consolidation radiologically n nPolypoid plugs of loose organizing connective tissue within alveolar ducts, alveoli (intraalveolar fibrosis) and often bronchioles n nNo interstitial fibrosis, no honeycomb lung n nIntraalveolar fibrosis also as a response to infections or inflammatory injury of the lungs n (inhaled toxins, drugs, collagen vascular diseases, GVHD) n Pulmonary involvement in collagen vascular diseases nSystemic lupus erythematodes, rheumatoid arthritis, progressive systemic sclerosis (scleroderma), dermatomyositis-polymyositis, mixed connective tissue disease n nNonspecific interstitial pneumonia, UIP, vascular sclerosis, organising pneumonia and bronchiolitis; n in RA: chronic pleuritis, pleural effusion, rheumatoid n nodules, IP, pulmonary hypertension Pneumoconioses nNon-neoplastic lung reaction (usually occupational) to inhalation of organic (mineral dusts) as well as inorganic particulates and chemical fumes and vapors n nAmount of the dust; size and shape (1-5μm), solubility, additional irritants n ne.g. quartz (form of crystalline silica): direct injury to tissue and cell membranes, triggering of macrophages to release of proinflammatory and fibrosing mediators) Coal workers´ pneumoconiosis (CWP) nUsually benign, minority cases develop pulmonary dysfunction, hypertension and cor pulmonale. nAsymptomatic antracosis (no fibrosis, antracotic pigment in pulmonary lymphatics and lmyph nodes) n nSimple CWP (coal macules and nodules); carbon-laden macrophages + collagen fibers; primarily ar respiratory bronchies; centrilobular emphysema n nComplicated CWP or progressive massive fibrosis with pulmonary dysfunction (multiple scars, dense collagenand pigment) n nCaplan´s syndrome: CWP+rheumatoid arthritis n nCoal dust inhalation; contamination by silica favor the progressive disease. n Silicosis nInhalation of silica (in both amorphous (less active) and crystalline forms (quartz, crystobalit, tridymite) followed by ingestion of silica particules by macrophages n nSilicotic nodules (concentric layers of hyalinized collagen with a dense capsule, polarization reveals silica particules) nHard collageneous scars (central softening and cavitation due to superimposed tbc or to ischemia; sheets of calcification in lymph nodes) n n nProgressive clinical course, even if the patient is no longer exposed n nCrystalline silica from occupational sources was suggested to be carcinogenic in humans nIncreased susceptibility to tbc in silicosis (depression of cell mediated immunity) - silicotuberculosis Asbestos – related diseases nLocalized fibrous plaques or diffuse pleural fibrosis nPleural effusions nParenchymal interstitial fibrosis (asbestosis) nLung carcinoma nMesothelioma nLaryngeal and perhaps extrapulmonary neoplasms n nBoth forms of asbestos (amphiboles (more pathogenic, 1x8 μm) and serpentines) are fibrogenic nAsbestos bodies: fusiform rods coated with an iron containing proteinaceous material n nDrug induced lung disease n (bleomycin, methotrexate, amiodarone (anti-arrhytmic,…) n nRadiation induced lung diseases n (acute and chronic radiation pneumonitis) n nGranulomatous diseases 1.Sarcoidosis (noncaseating granulomas; 90 % lung and hilar lymph nodes involvement; disordered immune regulation (cell mediated response to an unidentified agents) in genetically predisposed individuals (HLA-A1, HLA-B8, familiar and racial clustering) exposed to certain enviromental agents(e.g. mycobacteria, Rickettsia species, Propionibacterium acnes)) n other organs affected: spleen, liver, bone marrow, skin, eye and associated glands, salivary glands, muscle n2. Hypersenzitivity pneumonitis/extrinsic allergic alveolitis): inhalation of organic dusts and related occupational antigens (spores of thermophilic bacteria, fungi, animal proteins, bacterial products); farmer´s lungs, Pigeon breeder´s lung (birds), air conditionar lung (thermophilic bacteria) -Interstitial pneumonitis -Noncaseating granulomas -Interstitial fibrosis and obliterative bronchiolitis n n n Pulmonary eosinophilia nAcute eosinophilic pneumonia with respiratory failure (unknown etiology, steroid therapy) n nSimple pulmonary eosinophilia (Loffler syndrome) n nTropical eosinophilia (microfilariae) n nSecondary eosinophilia (in fungal, parasitic, bacterial infections, in hypersenzitivity pneumonitis) n nChronic eosinophilic pneumonia nSmoking related interstitial disease n nDesquamative interstitial pneumonia n(usually minimally fibrosis and no progressive course) n nPulmonary Langerhans cell histiocytosis/histiocytosis X n nRespiratory bronchiolitis-associated interstitial lung disease n(usually mild symptoms, cessation of smoking=improvemement) nPulmonary alveolar lipoproteinosis n nalveolar homogeneous granular precipitate within alveoli (PAS+, surfactant +) -Acquired (unknown etiology, autoimmune?) -Congenital (mutation in genes encoding surfactant proteins) -Secondary (silicosis and other inhalation syndromes, malignancies, immunodeficiency syndromes,…) Pulmonary embolism nHypercoagulable state -Primary (factor V Leiden, antiphospholipid syndrome,…) -Secondary (obesity, surgery, oral contraceptives, pregnancy,…) n n embolism Pulmonary infarction 17x20 Pulmonary hypertension nPulmonary blood pressure =1/8 of systemic blood pressure nPulmonary hypertension, cor pulmonale n nChronic obstructive and restrictive lung diseases (hypoxy + destruction of parenchyma) nAntecedent congenital or aquired heart disease (venostasis before left heart) nRecurrent thrombemboli nAutoimmune disorders involving pulmonary vasculature nVenooclusive lung disease (musculoelastic thickening of subpleural and interlobular septal veins) nPrimary idiopathic pulmonary hypertension n nMorphology: circular medial hypertrophy (arterioles and small arteries), subintimal fibrosis, plexogenic pulmonary arteriopathies in left to righ shunts or in primary PH (a tuft of capillary formations, small aneurysms with thromboses, fibrinoid necroses of arterioles) n Diffuse pulmonary haemorrhage syndrome nGoodpasture syndrome (autoimmune, antibodies against alpha-3 chain of collagen IV) -Proliferative, rapidly progressive glomerulonephritis -Necrotizing hemorrhagic interstitial pneumonitis n nIdiopathic pulmonary hemosiderosis n nVasculitis-associated hemorrhage -Hypersenzitivity angiitis -Granulomatosis with polyangiitis/Wegener granulomatosis -Churg-Strauss syndrome (allergic angiitis and granulomatosis) -Lupus erythematodes Pulmonary infections nFactors which favor the pneumonia n -Chronic diseases - -Immunologic defficiency, immunosuppressive treatment - -Unusual virulent infections, nosocomial infections - -Loss or suppression of the cough reflex (neuromuscular disorders, chest pain, drugs; could cause aspiration of gastric content,…) - -Injury of mucociliary apparatus (smoking, viral disease, genetic disorders, inhallation of hot or corrosive gases,…) - -Pulmonary congestion and edema - -Accumulation of secretion (bronchial obstruction, mucoviscidosis,…) - - Pneumonia syndromes nCommunity-acquired acute pneumonia n(streptococcus pn., haemophilus inf., Moraxella cat., Staphylococcus a., Legionella pn., Klebsiella pn., Pseudomonas ae.,….) nCommunity-acquired atypical pneumonia n(Mycoplasma pn., Chlamydia spp., Coxiella burnetti, viruses,…) nNosocomial pneumonia n(G- rods (Klebsiella spp., Serratia marcescens, E. coli, Pseudomonas spp.,…)) nAspiration pneumonia n(mixture od anaerobic and aerobic flora) nChronic pneumonia n(Nocardia, Actinomyces, granulomatous (mycobacterium tbc, atypical mycobacteria, Histoplasma capsulatum, Coccidioides immitis, Blastomyces dermatidis) nNecrotizing pneumonia and lung abscess n (mixture of aerobic and anaerobic flora, Staphylococcus a., Klebsiella pn., Streptococcus pyogenes and pneumoniae) nPneumonia in the immunocompromised host n (CMV, Pneumocystis c., Mycobacterium avium intracellulare, aspergillus, Candida a. and others listed above,…), n Pneumonia nAlveolar inflammation nBronchopneumonia and lobar pneumonia n n pneumonie -Patchy consolidation -Centred on bronchioles or bronchi -Purulent inflammation -Often in infancy or old age -Often secondary -Affects segments or whole lobe -4 stages (congestion, red hepatization, grey hepatization, resolution) -Uncommon in infancy and old age -Males more than females -90 % due to Streptococcus pneumoniae -Cough and fever with sputum -Fibrinous inflammation -Healing complicated by fibrotisation/ carnification of the lungs Complication: abscess, empyema, bacteremic dissemination Bronchopneumonia brpn1 brpn 40x Lobar pneumonia – fibrinous – crupous pneumonia plíce 40x HE 100x Carnification of the lung 200x 400x Atypical pneumonias nInflammatory changes predominantly interstitially – within alveolar walls n nComplication: ARDS n nClinically: -cough could be absent -fever, headache, muscle pain -poor finding at physical examination, severe X-ray finding (…atypical…) n Atypical pneumonias (usually interstitial) nInfective nIn non-immunosuppressed hosts -Viral and mycoplasma pneumonia -Legionnaires´disease (Legionella pneumoniae) - nNon-infective -Idiopatic interstitial pneumonitis and fibrosis (v.s. autoimmune) -Cryptogenic organizing pneumonia = bronchiolitis obliterans -Aspiration pneumonia (primarily non interstitial, often with lung abscess) -Eosinophilic (v.s. allergic) and hypersensitivity pneumonitis -Pulmonary involvement in collagen vascular diseases n(systemic lupus erythematodes, rheumatoid arthritis, progressive systemic sclerosis n(scleroderma), dermatomyositis-polymyositis, mixed connective tissue disease) - n Alveolar walls = interstitium in lungs…..in interstitial inflammation the inflammatory infiltrate withihn the alveolar walls…complication of alveolocapillary gas exchange In immunosuppressed hosts -Pneumocytis carinii -Fungi (e.g. Candida albicans, Aspergillus) -Viruses (CMV, HSV, varicella zoster) Interstitial pneumonia – Pneumocystis carinii HE 100x HE400x Abscess nAspiration of infective material nAntecedent primary bacterial infection nSeptic embolism nNeoplasia nOthers and cryptogenic n n Absceding bronchopneumonia plíce povrch abscesy plíce řez abscesy TBC of the lungs tbc1 tbc2 Tbc lymphadenitis 40x Tumors of the lung nEpithelial -Benign (adenomas) -Malignant (carcinomas) -squamous cell carcinoma -adenocarcinoma -small cell (neuroendocrine) carcinoma -large cell undifferentiared carcinomas nMesenchymal nOthers + secondary/metastatic lung tumours Neuroendocrine carcinoma (small cell carcinoma) 14_02 19x200 Squamous cell carcinoma 21x40 21x200x1 Adenocarcinoma of the lungs 22x40 12_01 Paraneoplastic syndrome nAntidiuretic hormone nAdrenocorticotropic hormone nParathormone nCalcitonin nGonadotropins nSerotonin and bradykinin n nNeuroendocrine neoplasias (carcinoids and small cell carcinomas) n Complications of lung cancer ca plic