Histopath 21: Resp Pathology Flashcards
What type of cells line the airways? the alveoli?
Airways = Ciliated respiratory epithelium
Alveoli = Type 1 Pneumocytes
Define pulmonary oedema + causes?
Accumulation of fluid in the alveolar spaces either due to leaky capillaries or back pressure from a failing left ventricle
This leads to poor gas exchange
Causes: LH failure (MAIN for path), alveolar injury (drugs), neurogenic following head trauma, high altitude
Intra-alveolar fluid is the main histological feature of what condition?
Pulmonary oedema
Causes of ARDS in adults
Infection Aspiration Trauma Inhaled irritant gases Shock DIC
What causes hyaline membrane disease in newborns?
Lack of surfactant (mainly in premature babies)
On a cellular level, what insult results in ARDS?
Acute damage to the endothelium and/or alveolar epithelium
The basic pathology is the same regardless of cause: diffuse alveolar damage
Lungs on post-partum examination was plum-coloured, heavy and airless
What was the cause of death?
ARDS
Outline the pathophysiology of ARDS.
Exudative phase – the lungs become congested and leaky
Hyaline membranes – form when serum protein that is leaked out of vessels end up lining the alveoli
Organising phase – organisation of the exudates to form granulation tissue sitting within the alveolar spaces
Define asthma
Chronic inflammatory airway disorder with recurrent reversible episodes of widespread narrowing of the airways
What is status asthmaticus ?
The term used to describe a severe attack of asthma where attacks occur one after the other
List some acute + chronic changes seen in asthma.
Acute: Bronchospasm Oedema Hyperaemia Inflammation
Chronic:
Muscular hypertrophy
Airway narrowing
Mucus plugging
Describe the main histological features of asthma
Lots of eosinophils and mast cells
Goblet cell hyperplasia
Mucus plugs within airways
Thickening of bronchial smooth muscle and dilatation of blood vessels
Define chronic bronchitis.
Chronic cough productive of sputum presents for most days for at least 3 months over 2 consecutive years
List some histological features of chronic bronchitis.
Dilated airways
Mucus gland hyperplasia
Goblet cell hyperplasia
Mild inflammation
List some complications of chronic bronchitis.
Recurrent infections
Chronic respiratory failure
Pulmonary hypertension and right heart failure (cor pulmonale)
Increased risk of lung cancer (independent of smoking)
Causes of emphysema (Type of COPD)
Smoking
Alpha-1 antitrypsin deficiency - may present as a young person w/ copd and liver issues and fhx
Rare: cadmium exposure, IVDU, connective tissue disorder
Define emphysema.
Permanent loss of alveolar parenchyma distal to the terminal bronchiole
Describe how the pattern of alveolar damage is different with smoking compared to alpha-1 antitrypsin deficiency
Smoking – centrilobular damage
Alpha-1 antitrypsin deficiency – panacinar (throughout the lungs)
List some complications of emphysema
Bullae (can rupture to cause pneumothorax)
Respiratory failure
Pulmonary hypertension and right heart failure (Cor Pulmonale)
Define bronchiectasis + what is a major RF and why + where is idiopathic bronchiectasis likley to affect
Pathalogical airway dilation secondary to recurrent infections
Major RF = CF - Permanent abnormal dilatation of the bronchi with inflammation and fibrosis extending into adjacent parenchyma
Lower lobe
Causes of bronchiectasis?
Infection (MOST COMMON):
Post-infectious (e.g. CF)
Abnormal host defence (e.g. chemotherapy, immunodeficiency)
Ciliary dyskinesia
Obstruction :
Post-inflammatory (aspiration)
Interstitial disease (e.g. sarcoidosis)
Asthma
List some complications of bronchiectasis.
Recurrent infections
Haemoptysis
Pulmonary hypertension and right heart failure (Cor Pulmonale)
Amyloidosis
Where is CFTR gene found and what is the most common mutation associated w/ CF?
7q3 - Delta F508
List some clinical manifestations of CF.
GI – meconium ileus, malabsorption Pancreas – pancreatitis Liver – cirrhosis Male reproductive system – infertility Recurrent chest infections
Causes of CAP + HAP
CAP:
- Strep pneumo
- Haemophilus influenzae
- Mycoplasma
HAP:
- Gram -ves (klebsiella, pseudomonas)
Bacteria involved in aspiration pneumonia
Mix of anaerobes + aerobes
What are the histopathological stages of lobar pneumonia?
Stage 1: congestion (hyperaemia and intra-alveolar fluid)
Stage 2: red hepatisation (hyperaemia, intra-alveolar neutrophils)
Stage 3: grey hepatisation (intra-alveolar connective tissue)
Stage 4: resolution (restoration of normal tissue architecture)
What is lobar pneumonia?
Infection is focused in a lobe of the lung
90-95% caused by S. pneumoniae
Widespread fibrinosuppurative consolidation
What is bronchopneumonia?
Infection is centred around the airways
Tends to be associated with compromised host defence (mainly the elderly) and is caused by low virulence organisms (e.g. Staphylococcus, Haemophilus, Pneumococcus)
It will show patchy bronchial and peribronchial distribution often involving the lower lobes
What is a granuloma?
Collection of macrophages and multi-nucleate giant cells
Describe the histological appearance of atypical pneumonia.
Interstitial inflammation (pneumonitis) without accumulation of intra-alveolar inflammatory cells
NOTE: causes include Mycoplasma, viruses, Coxiella and Chlamydia
What is a long term consequence of repeated small pulmonary emboli?
Pulmonary hypertension
What are the main types of lung cancer?
Non-small cell carcinoma:
- Squamous cell carcinoma (30%)
- Adenocarcinoma (30%)
- Large cell carcinoma (20%)
Small cell carcinoma (20%)
What components of cigarette smoke are responsible for its carcinogenicity?
Tumour initiators (polycyclic aromatic hydrocarbons)
Tumour promoters (nicotine)
Complete carcinogens (nickel, arsenic)
Which types of lung cancer are most strongly associated with smoking?
Which type of lung cancer tends to occur in non-smokers?
Squamous cell carcinoma
Adenocarcinoma
List some risk factors for lung cancer
Smoking Asbestos Radiation Air pollution Heavy metals Susceptibility genes (e.g. nicotine addiction)
Describe the sequence of histological changes that results in lung cancer
What feature of squamous epithelium makes it vulnerable to undergoing malignant changes?
Metaplasia 🡪 dysplasia 🡪 carcinoma in situ 🡪 invasive carcinoma
It does not have cilia leading to a build-up of mucus
Within the mucus carcinogens accumulate
Where do SCCs tend to arise? Where do adenocarcinomas tend to arise?
SCCs:
Centrally – arising from the bronchial epithelium
NOTE: there is an increasing incidence of peripheral squamous cell carcinomas (possibly due to deeper inhalation of modern cigarette smoke)
Adenocarcinoma:
Peripherally – around the terminal airways
NOTE: it tends to be multi-centric and extra-thoracic metastases are common and occur early
What is the precursor lesion for adenocarcinoma of the lung?
Atypical adenomatous hyperplasia (proliferation of atypical cells lining the alveolar walls)
Which mutations are associated with adenocarcinoma in smokers? non-smokers?
Smokers:
Kras
Issues with DNA methylation
P53
Non-smokers:
EGFR
What is large cell carcinoma of the lung?
Poorly differentiated tumour composed of large cells
There is no evidence of squamous or glandular differentiation - but probs from v poorly differentiated adeno or SCC
It has a poor prognosis
Where does small cell lung cancer tend to arise + prognosis?
Central – around the bronchi
NOTE: 80% present with advanced disease and it carries a poor prognosis - common mets to brain ribs and spinal cord
List some common mutations seen in small cell lung cancer
P53
RB1
What is the difference in the chemosensitivity of small cell lung cancer and non-small cell lung cancer?
Small cell – sensitive
Non-small cell – not very chemosensitive
Which molecular changes are important to test for in adenocarcinoma?
EGFR (responder or resistance)
ALK translocation
Ros1 translocation
Why is it important to know the tumour type precisely?
Some treatments can be fatal if the cancer is misdiagnosed
E.g. bevacizumab can cause fatal haemorrhage if used for squamous cell carcinoma
What is cancer of the pleura?
Mesothelioma
Histopathology shows smooth muscle hypertrophy and eosinophilia
What is the ddx?
Asthma
What is COPD?
COPD involves chronic bronchitis and emphysema
Histopatholgy reveals neutrophilic infiltrations into airways, loss of alveoli elastive fibres and lung parenchyma?
COPD
Note - in severe cases you can find eosinophilia too
Pathophysiology of CF?
Mutation leads to defective ion transport -> excessive resorption of water from secretions of exocrine glands -> abnormally thick mucous secretions -> affects all organ systems
Histopathology reveal mucous clogged airways and inflammatory cell infiltration
What is the ddx?
CF
Histopathology shows dilated fibrotic airways with mucous plugging - what is the ddx?
Bronchiectasis
A patient presents acutely w/ some resp symptoms + histopathology reveals heavy watery lungs with intra-alveolar fluid
What is ddx?
Acute pulmonary oedema
A patient presents acutely w/ some resp symptoms + histopathology reveals iron-laden macrophages and fibrosis
What is ddx?
Chronic pulmonary oedema
In this case IRON-LADEN MACROPHAGES are important - heart failure cells and pathogmnoic of pulmonary oedema
CXR = white out all lung fields
what is the ddx?
Diffuse alveolar damage:
- Adults = ARDS
- Neonates = RDS (hyaline membrane disease of newborn)
Histopathology shows pathcy bronchialand peribronchial distribution, acute inflammation of surrounding airways + w/in alveoli - what is ddx?
Bronchopneumonia
What are the different types of fibrosing lung disease + their features?
Idiopathic pulmonary fibrosis / cryptogenic fibrosis alveolitis:
- Chronic = SOB and cough
- 50+y, male predominance
- Diagnosis gold standard = High res CT +/- biopsy
Extrinsic allergic alveolitis / farmers lung
- organic allergens
Industrial lung disease / pneumoconiosis
- specific dusts in workspace (non-organic allergens)
What type of lung disease are fibrosising lung diseases?
Restrictive lung disease - FEV1/FVC >0.8
oat cells? ddx?
Small cell lung cancer
Which paraneoplastic syndromes are associated w/ small cell lung cancer?
SIADH
Lambert-Eaton - myasthenic syndrome
Cushings
1) A 35 year old non-smoker and non-drinker develops progressive shortness of breath, abdominal distension and spider naevi. What is the most likely underlying pathology?
Alpha-1 antitrypsin deficiency - Lung + Liver symptoms in a young non-smoker / drinker
2) Which gene on which chromosome is mutated in cystic fibrosis?
CFTR gene on chromosome 7
4) Which lung malignancy is the most common in non-smokers?
Adenocarcinoma
5) Which lung malignancy is most commonly associated with PTHrp secretion?
Squamous cell lung cancer - This causes the paraneoplastic syndrome seen with this cancer = Hypercalcaemia of malignancy
