Histo: Lung Pathology Flashcards
What type of epithelium lines the airways?
Ciliated respiratory epithelium
Which types of cells line the alveoli?
Type 1 pneumocytes
What is pulmonary oedema?
Accumulation of fluid in the alverolar spaces either due to leaky capillaries or back pressure from a failing left ventricle
This leads to poor gas exchange
List some causes of pulmonary oedema.
- Left heart failure
- Alveolar injury (e.g. drugs, smoke from a fire)
- Neurogenic following head trauma
- High altitude at a rapid pace (physiological response)
What is the main histological feature of pulmonary oedema?
Intra-alveolar fluid
List some causes of acute respiratory distress syndrome 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
Describe the appearance of the lungs on post-mortem examination in a patient who died from ARDS.
- Plum-coloured
- Heavy (>1kg)
- Airless
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
What are the outcomes of ARDS?
- Death
- Superimposed infection
- Resolution (restoration of normal lung function)
- Residual fibrosis (leads to chronic respiratory impairment)
Define asthma.
Chronic inflammatory airway disorder with recurrent reversible episodes of widespread narrowing of the airways
What is the term used to describe a severe attack of asthma where attacks occur one after the other?
Status asthmaticus
List some non-atopic triggers of asthma.
- Air pollution
- Occupational
- Exercise
List some acute changes seen in asthma.
- Bronchospasm
- Oedema
- Hyperaemia
- Inflammation
List some chronic changes seen in asthma.
- 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 (hyperaemia)
Define chronic bronchitis.
Chronic cough productive of sputum presents for most days for at least 3 months over 2 consecutive years
causes dilatation of the airways and excess mucus production
List some histological features of chronic bronchitis.
- Diluted airways
- Mucus gland hyperplasia
- Goblet cell hyperplasia
- Mild inflammation
List some complications of chronic bronchitis.
- Recurrent infections (this is what they present with, and die with!)
- Chronic respiratory failure
- Chronic hypoxia resulting in pulmonary hypertension and right heart failure (cor pulmonale)
- Increased risk of lung cancer (independent of smoking)
Define emphysema.
Permanent loss of alveolar parenchyma distal to the terminal bronchiole
List some causes of alveolar damage that can lead to emphysema.
- Smoking (damage to alveolar epithelium)
- Alpha-1 antitrypsin deficiency
- Rare: cadmium exposure, IVDU, connective tissue disorder
Describe how the pattern of alveolar damage is different with smoking compared to alpha-1 antitrypsin deficiency. And what is the pathophysiology of damage in smoking and A1AT
- Smoking - centrilobular damage (where the smoke goes)
- Alpha-1 antritrypsin deficiency - panacinar (throughout the lungs)
Smoking and alpha q antitrypsin means that proteases are no longer inhibited and this causes tissue damage
List some complications of emphysema.
- Bullae (can rupture to cause pneumothorax)
- Respiratory failue
- Chronic hypoxia —> Pulmonary hypertension and right heart failure
Define bronchiectasis.
- Permanent abnormal dilatation of the bronchi with inflammation and fibrosis extending into adjacent parenchyma
(chronic bronchitis is basically less severe)
Which part of the lungs tends to be affected most frequently in idiopathic bronchiectasis?
Lower lobe
List some 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 failue
- Amyloidosis
Where is the CFTR gene found?
7q3
What is the most common mutation associated with CF?
Delat F508
List some clinical manifestations of CF.
- GI - meconium ileus, malabsorption
- Pancreas - pancreatitis
- Liver - cirrhosis
- Male reproductive system - infertility
- Recurrent chest infections
List some causes of community-acquired bacterial pneumonia.
- Streptococcus pneumoniae
- Haemophilus influenzae
- Mycoplasma
List some causes of hospital-acquired bacterial pneumonia.
Gram negatives (Klebsiella, Pseudomonas)
Which types of bacteria tend to be implicated in aspiration pneumonia?
Mixture of aerobic and anaerobic
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 lobar pneumonia?
- Infection is focused in a lobe of the lung
- 90-95% caused by S. pneumoniae
- Widespread fibrinosuppurative consolidation
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)
List some complications of pneumonia.
- Abscess formation
- Pleural effusion
- Empyema
- Fibrous scarring
- Septicaemia
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
List some types of non-thrombotic emboli.
- Bone marrow
- Amniotic fluid
- Trophoblast
- Tumour
- Foreign body
- Air Fat
What are the main types of lung cancer?
- Non-small cell carcinoma
- Squamous cell carcinoma (30%)
- Adenocarcinoma (30%)
- Large cll 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?
- Squamous cell carcinoma
- Small cell carcinoma
S, S, S!
Which type of lung cancer tends to occur in non-smokers?
Adenocarcinoma
List some risk factors for lung cancer.
- Smoking
- Abestos
- Radiation
- Air pollution
- Heavy metals
- Susceptibility genes (e.g. nicotine addiction)
Describe the sequence of histological changes that results in lung cancer.
Metaplasia → Dysplasia → Carcinoma in situ → invasive carcinoma
What feautre of squamous epithelium makes it vulnerable to undergoing malignant changes?
- It does not have ciliar leading to a build-up of mucus
- Within the mucus carcinogens accumulate
Where do squamous cell carcinomas tend to arise?
Centrally - arising from the bronchial epithelium (which undergoes metaplasia to turn into a more resilient squamous cell to protect itself from the smoke)
NOTE: there is an increasing incidence of peripheral squmous cell carcinomas (possibly due to deeper inhalation of modern cigarette smoke)
Where does adenocarcinoma of the lung tend to arise?
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?
- Kras
- Issues with DNA methylation
- P53
Which mutation is associated with adenocarcinoma in 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
- It has a poor prognosis
Where does small cell lung cancer tend to arise?
- Central - around the bronchi
NOTE: 80% present with advanced disease (i.e. brain mets or bone) and it carries a poor prognosis
List some common mutations seen in small cell lung cancer.
P53
RB1
What is the difference in the chemosensistivity of small cell lung cancer and non-small cell lung cancer?
- Small cell - sensitive (but recur so often even after chemotherapy)
- Non-small cell - not very chemosensitive
Which molecular changes are important to test for in adenocarcinoma?
- EGFR (responder or resistance)
- ALK translocation
- Ros1 translocation
- PDL1 expression
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
what lung pathology do vapers get?
acute lung injury –> ITU admission
right and left lung lobes?
right has 3 left has 2
causes of chronic bronchitis?
chronic injury which elicits local inflammation - i.e. smoking, air pollution or occupational exposures
Inheritance pattern of CF
Autosomal recessive
what is a MAJOR risk factor for bronchiectasis
cystic fibrosis
what lung disorder are you at a large risk factor for in CF
bronchiectasis
CXR - white out of all lung fields - diagnosis?
diffuse alveolar damage (DAD) = acute respiratory distress syndrome = hyaline membrane disease of the newborn
lungs are filled with fluid and exudate
Causes of granulomatous lung disease
infection
sarcoid
foreign body
IVDU
Three important types of fibrosing lung disease?
Idiopathic pulmonary fibrosis (cryptogenic fibrosing alveolitis)
- 50% dead in 2-3y
Extrinsic allergic alveolitis (farmers’ lung)
Industrial lung diseases (pneumoconiosis)
What is included in virchow’s triad
Vessel damage
increased coagulation
Promotion of stasis
what is the pulmonary HTN bp
> 25mmHg at rest - pulmonary circulation usually reasonably low pressure
survival for small cell lung cancer?
1 year - 18m
Chemo works but it recurs so often
what treatment for EGFR mutation positive lung cancers?
TKI therapy (tyrosine kinase inhibitors)
What does the tumour having high levels of PDL1 mean?
It means you can give immunotherapy and help their own immune system make t cells against this marker
Which molecular changes are important to test for in squamous cell carcinoma?
PDL1
what % of lung cancers in the UK develop in non-smokers
10-20%
