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RESPIRATORY SYSTEM I

Belinda_Clarke@health.qld.gov.au

NORMAL LUNG Airways ciliated pseudostratified respiratory epithelium (basal cells, Kultschitsky/neuroendocrine cells, ciliated cells, serous cells, Clara cells, goblet cells, intermediate cells, brush cells), basement membrane, subepithelial tissue including smooth muscle, cartilage, elastin, bronchial glands. Alveoli Type I (squamous or membranous) and type II (cuboidal or granular) pneumocytes (epithelial cells), alveolar capillary membrane, endothelial cells, interstitial space (macrophages, pericytes, myofibroblasts, mast cells, occasional lymphocytes, few sensory nerves, collagen and elastin fibres, mucopolysaccharide gel); alveolar macrophages; pores of Kohn (interalveolar communications). Pulmonary arteries elastic, muscular (inner and outer elastic laminae), arterioles. Accompany bronchi/bronchioles. Bronchial arteries (systemic circulation). Veins in septa. Single elastic lamina. Lymphatics bronchovascular bundles, septa, pleura. Lymphoid tissue mucosa/bronchus-associated lymphoid tissue (BALT), intrapulmonary lymph nodes, hilar nodes. Serous and mucous bronchial glands. Ganglia, nerves sensory fibres in vagus nerve; motor supply through sympathetic (T2-T4) and parasympathetic (vagus) systems. Pleura (parietal and visceral) mesothelial cells, basement membrane, collagen, elastin, small blood vessels (mainly derived from bronchial arteries in visceral pleura), lymphatics, nerves, smooth muscle bundles, mast cells.

Defence mechanisms Sneezing Cough reflex Mucociliary apparatus/escalator IgA (local mucosal immune response) Alveolar macrophages

ACUTE LUNG INJURY PATTERNS Widespread injury to distal alveoli produces diffuse alveolar damage (DAD). More localised injury to peribronchiolar parenchyma produces organising pneumonia (OP). DIFFUSE ALVEOLAR DAMAGE Reaction to injury to epithelial cells (especially type 1 pneumocytes), endothelial cells and common alveolar capillary basement membrane to single major insult. Injury may come from either air or blood. Diffuse = whole alveolar septum involved not necessarily entire lung, but often widespread. Synonyms: Adult Respiratory Distress Syndrome (ARDS), respirator lung, shock lung, adult hyaline membrane disease, Da Nang lung, etc.

Causes of DAD: Infectious agents (viruses, Mycoplasma, Rickettsia, Legionella, any infection in immunocompromised patients, especially Pneumocystis) Toxic inhalants (chlorine, ammonia, high concentrations of inspired oxygen, war gases, smoke, etc.) Drugs (cytotoxics, amiodarone, penicillamine, gold, nitrofurantoin, heroin OD, etc.) Ingestants (Paraquat, kerosene, denatured rapeseed oil, etc.) Shock (traumatic, hypovolaemic, cardiogenic, septicaemia, DIC, head injury) Radiation (radiation pneumonitis) Miscellaneous (aspiration [Mendelsons syndrome], acute pancreatitis, burns, high altitude, SLE, etc.) Idiopathic (acute interstitial pneumonia/Hamman-Rich syndrome) Pathology of DAD: Macroscopic Heavy congested solid lung Histologic early acute exudative stage oedema, hyaline membranes, type 2 pneumocyte hyperplasia, capillary thrombi. later proliferative organising stage interstitial inflammation and fibrosis (after 1-2 weeks); eventual honeycomb lung if patient survives. ORGANISING PNEUMONIA Air space-filling fibrosing process involving distal bronchioles, alveolar ducts and peribronchiolar alveoli. Causes: Infection (viral, bacterial, fungal) Toxic inhalants (eg, nitrous oxide in silo-fillers disease) Drug toxicity (gold, amiodarone, sulfasalazine, cocaine abuse, etc.) Collagen vascular diseases (rheumatoid arthritis, SLE, polymyositis, etc.) Hypersensitivity pneumonitis (EAA) Bronchial obstruction (foreign material, tumour, etc.) Vasculitis syndromes (particularly Wegeners granulomatosis) Non-specific reaction pattern adjacent to other lesions (neoplasms, granulomas, infarcts, abscesses, etc.) Minor component of other pulmonary disease (e.g., eosinophilic pneumonia) Idiopathic (cryptogenic organising pneumonia COP/bronchiolitis obliteransorganising pneumonia BOOP) Clinical features of OP: Cough, dyspnoea, fever Patchy air space opacities on CXR, often peripheral Good prognosis, response to steroid treatment Pathology of OP: Serpiginous areas of loose fibroblastic proliferation forming plugs or polyps which occlude bronchiolar lumens and peribronchiolar air spaces.

Variable numbers of inflammatory cells in fibroblastic plugs and alveolar septa. Foamy macrophages in adjacent alveoli (obstructive pneumonitis).

INFECTION Routes inhalation (aerosolised organisms or contaminated oropharyngeal secretions), blood-borne, direct spread. Organisms bacteria, viruses, fungi. BACTERIAL INFECTIONS Patterns lobar vs. bronchopneumonia; organisms; clinical settings (community acquired vs. nosocomial). Descending: tracheitis -> bronchitis -> bronchiolitis -> bronchopneumonia which has a centrilobular pattern. Lobar pneumonia occurs in many adjacent lobules simultaneously because of the spreading capacity of the causative organism resulting in more extensive exudation through the pores of Kohn. Occur when there is breakdown in normal defence mechanisms. Lobar pneumonia Stages congestion/spreading inflammatory oedema (2-6 hours), red hepatisation (12 hours), grey hepatisation (1-10 days), resolution (after crisis or with therapy); associated pleurisy. Complications incomplete resolution leading to organisation and carnification; empyema; pericarditis; bacteraemia/septicaemia. Bronchopneumonia Bronchocentric (no pleurisy unless confluent) Complications organisation, abscess formation. Patterns of acute bacterial pulmonary infection: ORGANISM Staphylococcus, incl. MRSA Beta-haemolytic Streptococcus Strep. pneumoniae (pneumococcus) Haemophilus influenzae Klebsiella pneumoniae (Friedlander bacillus) Bordetella pertussis (whooping cough) Pseudomonas, Proteus, E. coli Legionella pneumophila (Legionnaires disease) PATTERN OF DISEASE Lobular consolidation with abscesses Bronchopneumonia or lobar pneumonia Lobar pneumonia Mucopurulent bronchitis/bronchiolitis Bronchopneumonia Lobar or lobular consolidation, abscesses Cavitation (pulmonary gangrene) Bronchitis, bronchiolitis Lobular consolidation Infarct-like areas Bronchopneumonia Lobar pneumonia, DAD, OP

Filamentous bacteria: Nocardia in immunocompromised hosts, causes necrotising acute bronchopneumonia with abscess formation +/- granulomas. Actinomyces usually in immunocompetent hosts, causes microabscesses.

ATYPICAL PNEUMONIA Characterised by association of pneumonitis, fever and usually normal peripheral white cell count; often show interstitial inflammation as well as, or instead of, alveolar exudate. Chlamydia (obligate intracellular bacteria) C. pneumoniae usually bronchiolitis or mild interstitial pneumonitis; ?association with coronary atherosclerosis. C. psittaci psittacosis (ornithosis, parrot fever): haemorrhagic pneumonitis sensitive to erythromycin, tetracycline; infection from birds. Rickettsia Coxiella burnetii (Q fever) Mycoplasma pneumoniae (small extracellular bacterium lacking a cell wall) Droplet infection -> adherence to ciliated respiratory epithelial cells Bronchiolitis, bronchopneumonia, DAD

VIRAL INFECTIONS Droplet infection of immunocompetent host, eg, influenza, parainfluenza Opportunistic infection, eg, CMV, varicella, HSV Viral cytopathic changes intranuclear or cytoplasmic inclusions, smudge cells. Secondary bacterial infection VIRUS Influenza PATTERN OF DISEASE Necrotising tracheobronchitis and bronchiolitis DAD (diffuse alveolar damage) Organising pneumonia (OP) Secondary bacterial bronchopneumonia, abscesses Laryngotracheobronchitis, bronchiolitis Interstitial pneumonitis with giant cells, DAD Necrotising bronchiolitis with giant cells Interstitial pneumonitis, OP Bronchiolitis and peribronchiolitis with giant cells Interstitial pneumonitis, DAD Necrotising bronchitis/bronchiolitis Interstitial pneumonitis, DAD Necrotising bronchopneumonia, DAD Later calcified nodules Necrotising tracheobronchitis Necrotising bronchopneumonia Interstitial pneumonitis, DAD Interstitial pneumonitis, may be mild -> DAD DAD

Parainfluenza Respiratory syncytial virus (RSV) Measles Adenovirus Varicella-zoster (chickenpox) Herpes simplex (HSV-1)

Cytomegalovirus (CMV) Coronavirus (SARS)

FUNGAL INFECTIONS Often occur in immunocompromised hosts. FUNGUS Aspergillus PATTERN OF DISEASE Allergic/hypersensitivity reaction: Allergic bronchopulmonary aspergillosis (ABPA) bronchocentric granulomatosis Mucoid impaction of bronchi Saprophytic colonisation: Aspergilloma (fungus ball) Invasive aspergillosis: Acute aspergillus pneumonia (vascular invasive) Necrotising pseudomembranous tracheobronchitis Chronic necrotising granulomatous inflammation (semiinvasive aspergillosis) Candida Bronchitis Pneumonia Cryptococcus Cryptococcoma (toruloma) necrotising or non-necrotising neoformans granuloma Pneumocystis carinii Lobar or lobular consolidation with foamy exudate in alveoli and interstitial pneumonitis; DAD