W9 - Respiratory pathology Flashcards
Name the 3 classifications adult non-neoplastic lung diseases are divided into?
1. Airway diseases i.e. asthma, COPD, bronchiectasis
2. Parenchymal disease i.e. pulmonary oedema & diffuse alveolar damaage (ARDS, HMD), COPD-emphysema, granulomatosis diseases, fibrosing intersititial lung disease
3. Pulmonary vascular disease
What are some causes (7) of asthma
- Allergens and atopy (house dust mite)
- Pollution
- Drugs - NSAIDs
- Occupational - inhaled gases/fumes
- Diet
- Physical exertion - “cold”
- Intrinsic/Underlying genetic factors
Explain the pathogenesis behind asthma, from sensitisation to allergen to later re-exposure.
Sensitisation to allergen = allrgen picked up by DC => TH2 primed => B cell primed => B cell class switch to IgE secreting => mast cell + eosinophils recruited and activated.
Re-exposure to allergen = allergen-specific IgE bind to alletgen => mast cells degranulate on contact with antigen => mediators released cause vascular permeability, eosinophil and mast cell recruitment => bronchospasm
What physiological changes (3) take place in the lung in the late phases of asthma?
Late phases:
1) tissue damage
2) increased mucus production
3) muscle hypertrophy
Name 3 mascropcopic features of asthma in asthma-related deaths
- Mucus plug
- Hyperinflated lung
- Mucus plug in-situ
Name 4 histological features of asthma
- Hyperaemia (increased blood flow to lung tissue)
- Eosinophilic inflammation + goblet cell hyperplasia (mucus)
- Hypertrophic contricted muscle
- Mucus plugging
What are common causes (3) of COPD?
- Smoking
- Air pollution
- Occupational exposures
The 2 main types of COPD are…
Chronic bronchitis
Emphysema
3 histological features of COPD Chronic bronchitis
- Dilatation of airways
- Hypertrophy mucous glands
- Goblet cell hyperplasia
4 possible complications of chronic bronchitis COPD
- Repeated infections
- Chronic hypoxia
- Pulmonary hypertension and cor pulmonale (due to chronic hypoxia)
- Increased risk of lung cancer
What are the common causes of bronchiectasis?
1. Congenital
2. Inflammatory:
A) Post-infectious (esp in children or CF patients)
B) CIliary dyskinesia - primary and 2ndary
C) Obstruction (extrinsic/intrinsic)
D) Post-inflammatory (aspiration)
E) Secondary to bronchiolar disease & interstitial fibrosis (sarcoidosis)
F) systemic disease (connective tissue disorders)
G) asthma
Name 4 complications of bronchiectasis
- Recurrent infections
- Haemoptysis
- Pulmonary hypertension and cor pulmonale
- 2ndary amyloidosis
What are the main causes (4) of pulonary oedema?
- Left heart failure (typically acute-on-chronic LHF)
- Alveolar injury
- Neurogenic (i.e. post-severe head injury)
- High altitude (poor compensation of lungs => flooding of lungs)
Which is more severe - pulmonary oedema or diffuse alveolar damage? and why?
Diffuse alveolar damage - ACUTE diffuse lung injury with rapid onset of respiratory failure, often requiring ventilation on ITU.
What is a typical CXR finding of diffuse alveolar damage?
White-out on all lung fields
What is the pathogenesis behind diffuse alveolar damage?
Acute damage to endothelium +/- alveolar epithelium => exudative inflammatory reaction
What does diffuse alveolar damage cause in 1) neonates and 2) adults
1) Neonates => Hyaline membrane disease of newborn
2) Adults => Acute respiratory distress syndrome (ARDS) aka “Shock lung”
What is the cause of hyaline membrane disease of newborn? Which group of neonates is it more common in?
insufficient surfactant production => sitff lungs => 2ndary alveolar epithelial damage
premature babies
What are the causes of ARDS (7) in adults?
Numerous causes:
- Infection (local (COVID) or generalised sepsis)
- Massive aspiration
- Trauma
- Inhaled irritant gases (smoke)
- Shock (hypovolaemic)
- Blood tranfusion
- DIC
- Idiopathic
What are the stages (4) that lungs go through in diffuse alveolar damage?
Capillary congestion => Exudative phase => Hyaline membranes (dead debris) => Organising phase (fibrotic changes)
What are the outcomes of DAD?
40% mortality
superimposed infection
residual fibrous scarring of lung => chronic respiratory impairment
Name 4 patterns of lung involvement in BACTERIAL pneumonia
- Bronchopneumonia (most common pattern)
- Lobar pneumonia
- Abscess formation
- Granulomatous inflammation
Bronchopneumonia and lobar pneumonia - what pattern do you see in each?
Bronchopneumonia = Patchy/spotty bronchial and peribronchial distribution, often lower lobes
Lobar pneumonia = massive consolidated pattern
What organisms (4) cause bronchopneumonia?
Often low virulence organisms:
Staphylococcus
Haemophilius
Streptococcus
Pneumococcus
Why don’t we see lobar pneumonia as frequently?
b/c we usually begin treating with abx before the infections spreads throughout entire lobe.
Which organisms (1) cause lobar pneumonia?
More fatal pathogens than those causing bronchopneumonia
i.e. 90-95% pneumococci (S. pneumoniae)
What histopathological features (4) do you see in lobar pneumonia?
- Congestion - hyperaemia, inter-alveolar fluid
- Red hepatisation - hyperamia, intra-alveolar neutrophils
- Grey hepatisation - intra-alveolar connective tissue
- Resolution - restoration of normal architecture with some fibrosis
What are some complications (5) of pneumonias?
- Abscess formation
- Pleuritis and PE
- Infected PE = EMPYEMA
- Fibrous scarring
- Septicaemia
COPD has two components - name them.
Airway component = chronic bronchitis
Alveolar parenchymal component = Emphysema
What is COPD Emphysema?
Permanent loss of the alveolar parenchyma distal to the terminal bronchiole
In terms of histopathology, how can you differentiate emphysema caused by cigarette smoke vs emphysema xaused by alpha-1 antitrypsin deficiency?
Smoking => comes in via airways => loss centred on bronchioles => CENTRILOBULAR
Alpha-1 antitrypsin deficiency => affects all lung tissue => diffuse loss of alveolae => PANACINAR
Name risk factors (3) for developing COPD emphysema?
- SMOKING
- Pollution
- Alpha-1 anti-trypsin deficiency
Complications (4) of emphysema
- Bullae => may lead to pneumothorax
- Respiratory failure => due to loss of alveolar wall for gas exchange
- Pulmonary hypertension => due to the vascular changes in response to hypoxia
- Cor pulmonale => as a result of 3
What is a granuloma in terms of histopathology?
Collection of 1) histiocyte/macrophages +/- 2) multinucleate giant cells
3) necrotising OR non-necrotising
Describe idiopathic pulmonary fibrosis: macro & micro changes
macro: basal and peripheral fibrosis and cyst formation
micro: interstitial fibrosis at varying stages
What are the causes (3) of granulomatous lung disease?
- Infection (TB, fungal infection)
- Sarcoidosis
- Foreign body - aspiration or IVDU
What is fibrosing lung disease? Name 3 types
Parenchymal diseases that are chronic and progressive fibrosing diseases of lung
- Idiopathic pulmonary fibrosis (cryptogenic fibrosing alveolitis)
- Extrinsic allergic alveolitis (Farmer’s lung)
- Industrial lung diseases (pneumoconiosis)
Name 3 types of pulmonary vascular disease
- Pulmonary thromboembolism
- Pulmonary hypertension
- Pulmonary vasculitis
Compare and contrast small vs large pulmnary embolus in terms of:
- area occluded
- presentation
- type of infarct
Small:
- peripheral pulmonary arterial occlusion (small)
- Presents with: pleuritic chest pain, acute SOB, chronic progressive SOB
- Haemorrhagic infarct
Large:
- occludes main pulmonary trunk = saddle embolus
- Presents with: sudden death, acute RHF, CVS shock
- non-haemorrhagic infarct
What is a complication of repeated small pulmonary emboli?
Increasing occlusion of pulmonary vascular bed => pulmonary hypertension
What defines pulmonary hypertension?
mean pulmonary arterial pressure >25 mmHg at rest
What cell type do the commonest malignant lung tumours originate from?
Epithelial tumours (90-95%) of all malignant tumours
Name the types of non-small cell and small cell carcinomas
Non-small cell carcinoma (80%):
- Squamous cell carcinoma (30%)
- Adenocarcinoma (30%)
- Large cell carcinoma (20%)
Small cell carcinoma (20%):
- small cell carcinoma
Describe the pathway of development of squamous cell carcinoma with exposure to cigarette smoke
normal epithelium => hyperplasia => squamous metaplasia => dysplasia => carcinoma in situ => invasive carcinoma (k-ras mutation)
Which is more aggressive - small cell or non-small cell carcinomas?
small cell carcinomas
Which part of the lung do adenocarcinomas typically affect? What is the name of that initial area? How does it spread?
Proliferation of atypical cells lining the alveolar walls => increase in size then finally become invasvie
Precursor lesion (red) = atypical adenomatous hyperplasia (AAH)
AAH => grows in area = non-mucinous adenocarcinoma in-situ => invades into blood vessels = mixed pattern invasive adenoCa
Which 2 types of lung cancer is smoking most commonly associated with?
- NSCLC squamous cell carcinoma
- SCLC
Name causes (5) of lung cancer in non-smokers?
- Asbestos
- Radiation (radon exposure, therapeutic radiation)
- Air pollution
- Heavy metals (arsenic, nickel)
- Genetic susceptbility (familial cases are rare)
Where does lung squamous cell carcinoma usually take place?
How does it behave in terms of spread?
traditionally centrally located arising from bronchial epithelium (centrally around large bronchi)
local spread, metastasise later.
Describe risk factor of adenocarcinoma lung cancer
- Smoking + others
BUT commoner in FAR EAST, FEMALES, and NON-SMOKERS
Which part of lung does large cell carcinoma affect?
What is its’ histological features?
Prognosis?
peripheral or central tumours
Poorly differentiated tumours composed of large cells = no histological evidence of glandular or squmamous differentiation
Rank NSCLC from best to worst prognosis
Squamous cell carcinoma (best) > adenocarcinoma > large cell carcinoma
NSCLC vs SCLC - which has a poorer prognosis?
SCLC - very aggressive tumour!
Where in the lung do small cell carcinomas usually occur?
How do they spread?
often central near bronchi
small poorly differentiated cells that divide rapidly (lots of mitoses)
Name the risk factors (1) for SCLC and the genetic mutations associated with it
- smoking
- genetic mutations: p53 and RB1 mutations
Which lung cancers are more chemosensitive?
SCLC - however 80% present with metastases so it doesn’t prolong life by too much
All lung cancers are now sent for molecular testing - name 3 important test and its implications in terms of treatment for lung cancers
- checking for certain EGFR mutations => EGFR is a receptor and some targeted therapies with tyrosine kinase inhibitors (TKIs, such as gefitinib) can block these pathways and BLOCK/SLOW tumour growth
- Checking for ALK translocation
- Checking for Ros1 translocation
- both 2 + 3 respond to Crizotinib (TK receptor inhibitor)
what marker do lung tumour cells usually express to modulate immune response? What is the direct effect?
Tumour cell expresses PDL-1 => interacts with PD-1 on cytotoxic CD8 T cells to suppress them = turns off entire immune cascase (DCs, Tregs, TH2, macrophages, etc).
Which molecular/immuno testing are adenocarcinoma and squamous cell carcinoma now sent for?
Adenocarcinoma:
- EGFR mutations - responder mutation or resistance mutation
- Alk translocation
- Ros1 translocation
- PDL-1 expression
Squamous cell carcinoma:
- PDL-1 expression
