ACEM Primary
Respiratory Pathology
Pulmonary Congestion and Oedema
= Leakage of excessive interstitial fluid which accumulates in alveolar spaces
Can result from:
- Haemodynamic disturbances
- Increased hydrostatic pressure = L sided HF, volume overload, pulmonary vein obstruction
- Decreased oncotic pressure = Hypoalbuminemia, nephrotic syndrome, liver disease, protein losing enteropathies
- Direct increases in capillary permeability
- Infection, inhaled gases, liquid aspiration, radiation
- Septicaemia, blood transfusion related burns, drugs, shock and trauma
- Undetermined
- High altitude, neurogenic
Acute Lung injury (ALI) and ARDS
= Initiated by injury of pneumocytes and pulmonary endothelium -> vicious cycle of increasing inflammation and damage
- Abrupt onset hypoxemia + bilateral pulmonary infiltrates
- ARDS is a manifestation of ALI, caused by sepsis, trauma or diffuse infection
- Pathogenesis:
- Endothelial activation
- Adhesion and extravasation of neutrophils
- Accumulation of intra-alveolar fluid + formation of hyaline membranes
- Resolution of injury
Obstructive Airways Disease
= Increase in resistance to airflow due to partial/ complete obstruction of airways, FEV1/FVC <0.7
Emphysema
- Irreversible enlargement + destruction of airspaces distal to terminal bronchiole
- Classified:
- Centriacinar (95%) – heavy smokers
- Panacinar – alpha 1 anti-trypsin deficiency
- Paraseptal – distal acinus, cause of spontaneous pneumothorax
- Irregular – scarring
- Pathogenesis:
- Smoking/ air pollutant/ genetic predisposition ->
- Oxidative stress, apoptosis
- Inflammation
- Protease/ anti-protease imbalance
- Alveolar destruction
- Morphology:
- Voluminous lungs, large alveoli separated by thin septa with focal centriacinar fibrosis
- CXR: hyperinflation, small heart
- Symptoms: Occur when 1/3 parenchyma damaged
- Dyspnoea, cough/ wheeze
- Barrel chest, weight loss (cancer)
- Prolonged expiration, tripod position with pursed lips “pink puffers”
- Cor pulmonale, CCF related to pulmonary hypertension
Chronic bronchitis
- Persistent cough with sputum production for at least 3 months in at least 2 consecutive years, without another cause
- Pathogenesis:
- Exposure to noxious smoke or dust
- Mucous hypersecretion
- Inflammation
- Infection
- Morphology:
- Hyperplasia of mucous glands, increased Reid Index (ratio of mucous gland layer to epithelium) + bronchiolitis obliterans and persistent inflammation
- CXR: Prominent vessels, large heart
- Symptoms:
- Cough with copious sputum, dyspnoea
- Hypercapnia, hypoxia and mild cyanosis “Blue bloater”
Asthma
- Chronic disorder of conducting airways, usually caused by immunological reaction
- Episodic reversible bronchoconstriction due triad of increased airway sensitivity, inflammation of bronchial walls and increased mucous secretion
- Categories:
- Atopic = allergen sensitisation and immune activation
- Associated with allergic rhinitis or eczema
- IgE mediated hypersensitivity = exaggerated TH2 response to normally harmless environmental stimuli. IgE binds Fc R on mast cells and on repeat exposure to allergen, triggers release of granule contents -> cytokines and mediators.
- Early phase: bronchoconstriction, increased mucous production, vasodilation and increased vascular permeability
- Late phase: recruitment of leukocytes, eosinophils
- Susceptibility is multigenic
- Common industrialised societies
- Atopic = allergen sensitisation and immune activation
- Non atopic = no evidence of allergen sensitisation
- Viral infections: virus induced inflammation of respiratory mucosa lowers threshold of subepithelial vagal R to irritants
- Drug induced: sensitivity to small doses of aspirin/ NSAID -> inhibit cyclo-oxygenase pathway of arachidonic acid metabolism -> decrease PGE2 which normally inhibits enzymes that generate proinflammatory mediators -> asthma
- Inhaled air pollutants (occupational)
- Morphology:
- Sub-basement membrane fibrosis, hypertrophy of bronchial glands and smooth muscle hyperplasia Curschmann spirals and Charcot- Leyden crystals
Bronchiectasis
- Destruction of smooth muscle and elastic tissue by chronic necrotising infection leads to permanent dilation of bronchi and bronchioles
- Pathogenesis:
- Congenital/ hereditary conditions (primary ciliary dyskinesia)
- Infection (aspergillosis)
- Bronchial obstruction
- Immune conditions
- Idiopathic
- Symptoms:
- Severe, persistent cough productive of foul-smelling sputum +/- haemoptysis
- Dyspnoea, orthopnea
Restrictive Airways Disease
= Reduced compliance and forced vital capacity, ratio of FEV1/FVC is normal
Caused by chronic interstitial pulmonary diseases = inflammation and fibrosis of pulmonary interstitium
- Idiopathic pulmonary fibrosis (IPF)
- Patchy interstitial fibrosis and formation of cystic spaces = honeycomb lung
- Cause unknown, poor prognosis
- Interstitial or cryptogenic organising pneumonia
- Connective tissue disease = SLE, RA, scleroderma
- Pneumoconioses
- Coal Workers (Anthracosis)
- Silicosis (sand blasters, mine workers)
- Asbestos related
Pulmonary Infections
Pneumonia can occur whenever pulmonary antimicrobial defences are impaired:
- Loss of cough reflex (coma, anaesthesia, neuromuscular disorders, drugs, chest pain)
- Injury to mucociliary apparatus (cigarette, hot/ corrosive gas, viral disease, genetic defect)
- Accumulation of secretions (CF, bronchial obstruction)
- Interference with phagocytic action (ETOH, smoking, anoxia or oxygen intoxication)
- Pulmonary congestion and oedema
Bacterial CAP
| Strep pneumoniae | Gram positive diplococci Most common cause of CAP Pneumococcal vaccine used for high risk individuals Distribution is usually lobar Encapsulated, asplenic patients at higher risk |
| H influenzae | Pleomorphic gram negative Vaccination against B serotype has reduced disease significantly Non typeable forms increasing Can follow viral pneumonia Paediatric emergency as high mortality rate, prior to vaccination could cause septicaemia, endocarditis, pyelonephritis and arthritis Common cause of IECOPD |
| Moraxella catarrhalis | Gram negative diplococcus Elderly, IECOPD |
| S aureus | Gram positive cocci High incidence of complications (abscess, empyema and IE in IVDU) Cause of HAP |
| K pneumoniae | Gram negative bacterial pneumonia Common in alcoholics, debilitated and malnourished Thick gelatinous sputum |
| P aeruginosa | Encapsulated Gram negative rod Cause of HAP Common in CF, burns and immunocompromised patients High propensity to cause septicaemia |
| Legionella | Gram negative Flourishes in artificial aquatic environments Immunosuppressed, organ transplant recipients |
Morphology
- Two patterns = lobar and bronchopneumonia (patchy consolidation)
- Lobar pneumonia: 4 stages, antibiotics halts progression.
- Congestion (vascular engorgement)
- Red hepatisation (neutrophils, red cells and fibrin into alveolar spaces)
- Grey hepatisation (disintegration of red cells, fibrinosuppurative exudate)
- Resolution
- Complications: Abscess, empyema and bacterial dissemination
Bacterial atypical pneumonia
Mycoplasma, Chlamydia pneumoniae, Coxiella burnetii
Children and young adults mostly
Sporadically occur as epidemics
Viral atypical pneumonia
| Influenza A | Major cause of pandemics/ epidemics Influenza genome encodes number of proteins – most important virulence factors are haemagglutinin and neuraminidase proteins Epidemics caused by spontaneous mutations that alter antigenic epitopes on these proteins = new viral strains via antigenic drift Pandemics caused by genes being replaced altogether through recombination with animal influenza viruses via antigenic shift Pathogenesis: Infects pneumocytes -> inhibits Na channels = fluid accumulation in alveolar lumen and cell death/ inflammation Clearance -> T cells kill virus infected cells + intracellular anti-influenza protein (Mx1) is induced in macrophages by IFN a and b Consequences: ARDS More fatal if superimposed bacterial infection occurs |
| Human metapneumovirus | Paramyxovirus Common seen in young children, elderly and immunocompromised patients |
| SARS | Coronavirus Causes severe acute respiratory syndrome |
| Other | Adenovirus, rhinovirus, RSV |
Morphology
- Interstitial inflammation
- Laryngotracheobronchiolitis, bronchiolitis
Hospital-acquired pneumonia
Due to MRSA, Pseudomonas, S. pneumoniae and Enterobacteriaceae commonly
| VAP | Gram negative bacilli |
| Aspiration | Necrotising, fulminant clinical course >1 organism, aerobes more common than anaerobes Frequent cause of death Lung abscess is common |
| Pulmonary abscess | Local suppurative process that produces necrosis of lung tissue Common organisms include aerobic/ anaerobic streptococci, S aureus and gram negatives Risk factors = oropharyngeal or dental procedures, aspiration, antecedent lung infection, septic embolism, neoplasia |
| Chronic pneumonia | Localised lesion usually granulomatous by bacteria (M tuberculosis) or fungi (Histoplasma capsulatum and others) Histoplasmosis: Ohio, Mississippi River and Caribbean Acquired by inhalation of soil particles contaminated by bird/ bat droppings, containing spores Self limiting, latent primary pulmonary involvement -> coin lesions on CXR Chronic progressive secondary disease, localised to apices -> cough, fever, night sweats Spread to extrapulmonary sites Widely disseminated in immunocompromised patients Blastomycosis: Central and Southwest US 3 clinical forms = pulmonary, disseminated and primary cutaneous (rare) Pulmonary = abrupt illness with productive cough, headache, chest pain, weight loss, fever, abdominal pain, night sweats and anorexia CXR – lobar consolidation, multi-lobar/peri-hilar infiltrates Coccidioidomycosis: Southwest US and Mexico Delayed hypersensitivity reaction, most asymptomatic Lung lesions, fever, cough, erythema nodosum/ multiforme |
| Immunocompromised host – pulmonary infiltrates | Differential includes infection, drug reactions or cancer Infectious aetiology: P aeruginosa, Mycobacterium sp, Legionella, Listeria monocytogenes CMV, HSV P jiroveci, Candida, Aspergillus, Phycomycetes, Cryptococcus neoformans HIV: S pneumoniae, S aureus, H influenza and gram negative rods Not all pulmonary infiltrates are infectious in HIV – consider Kaposi sarcoma, non- Hodgkin lymphoma and lung cancer |
Lung Tumours
- 90-95% are carcinomas
- 5% are bronchial carcinoids
- 2-3% are mesenchymal or miscellaneous
- Pathogenesis
- Arise by accumulation of genetic abnormalities
- Risk factors = smoking, radiation, asbestos exposure, molecular genetics and precursor lesions
- Often arise around lung hila
Classification
| Adenocarcinoma | Squamous cell carcinoma | Large cell carcinoma | Small cell carcinoma |
| Glandular differentiation Common in women and non-smokers Peripherally located lesions | Closely correlated with smoking More common in menCentral (from segmental or subsegmental bronchi) or peripheral lesions | Undifferentiated malignant epithelial tumour | Highly malignant Closely correlated with smoking Arise in major bronchi or lung peripheries Most aggressive, metastasize widely |
Staging = TNM system
Clinical course
- Present with cough, weight loss, dyspnoea, chest pain
- Adenocarcinoma and squamous cell patterns ten to remain localised – slightly better prognosis
- Can be associated with paraneoplastic syndromes:
- SIADH
- Cushing’s syndrome
- Hypercalcaemia due to parathyroid hormone or parathyroid related peptide
- Gynaecomastia due to gonadotropins
- Carcinoid syndrome (serotonin and bradykinin)
Consequences
- Obstruct bronchial lumen causing atelectasis and infection
- Focal areas of haemorrhage or necrosis
- Extension to pleural surfaces, cavity or pericardium
- Haematogenous and lymphatic spread to liver, brain and bone
- Rib destruction
- Horner syndrome
- SVC compression
Last Updated on August 20, 2021 by Andrew Crofton
Andrew Crofton
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