Histo: Lung Pathology Flashcards
What type of epithelium lines the airways?
Ciliated respiratory epithelium
Which types of cells line the alveoli?
Type 1 pneumocytes (squamous)
Type 2 pneumocytes (produce surfactant)
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)
- Neurogenic following head trauma
- High altitude
- ARDS
- Sepsis
What is the main histological feature of pulmonary oedema (acute + chronic)?
acute = Intra-alveolar fluid
chronic = iron laden macrophages (“HF cells”)
List some causes of acute respiratory distress syndrome in adults.
Pulmonary causes
- Pneumonia
- Aspiration
- Inhaled irritant gases
Systemic causes
- Sepsis (most common)
- Shock
- TRALI
- Pancreatitis
- Trauma
What causes hyaline membrane disease (neonatal respiratory distress syndrome) 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.
Describe XR
- Plum-coloured
- Heavy (>1kg)
- Airless
XR = “white out”
Outline the pathophysiology of ARDS.
EHO =”ARDS, Ever Had Oreos?”
* Exudative phase - inflammation leads to damaged alveoli and vessels - fluid leaks into air spaces (pulmonary oedema)
* Hyaline membrane - exudate proteins form hyaline membranes in alveoli
* Organising phase - proliferation of type 2 pneumocytes and fibroblasts to form granulation tissue and progessive fibrosis
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.
- Irritants in air (pollution, cigarette smoke)
- Viral infection
- Exercise
- Cold air
- Drugs (NSAIDs)
- Occupational
- Diet
List some acute changes seen in asthma.
- Bronchospasm
- Oedema
- Hyperaemia (increased blood flow to the airways - causes redness/swelling)
- 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
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)
Define emphysema.
Permanent loss of alveolar parenchyma distal to the terminal bronchiole
List some causes of alveolar damage that can lead to emphysema.
- Smoking
- 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.
- Smoking - centrilobular damage
- Alpha-1 antritrypsin deficiency - panacinar damage
List some complications of emphysema.
- Bullae (can rupture to cause pneumothorax)
- Respiratory failue
- Pulmonary hypertension and right heart failure
Define bronchiectasis.
- Permanent abnormal dilatation of the bronchi leading to chronic respiratory symptoms
Which part of the lungs tends to be affected most frequently in idiopathic bronchiectasis?
Lower lobe
List some causes of bronchiectasis.
- Infection (MOST COMMON)
- Immunodeficiency
- Abnormal mucus clearance
- CF
- Primary cilliary dyskinesia
- Obstruction
- COPD
- Tumour
- Aspiration (post-inflammatory)
- Connective tissue disease (SLE, RA)
- Asthma
List some complications of bronchiectasis.
- Recurrent infections and abscess
- Haemoptysis
- Pulmonary hypertension and right heart failue
- Amyloidosis
Where is the CFTR gene found?
7q3
What is the most common mutation associated with CF?
Delta 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?
Causes?
Histology?
- 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 - increased blood flow and alveoli start to fill with exudate and bacteria
- Stage 2: red hepatisation - alveoli filled with exudate rich in RBCs, fibrin, bacteria, and WBCs
- Stage 3: grey hepatisation - alveoli filled with exudate rich in WBC (RBC and bacteria have been degraded)
- Stage 4: resolution - fibrinolysis and macrophage removal of exudate
List some complications of pneumonia.
- Abscess formation
- Pleural effusion
- Empyema
- Fibrous scarring
- Septicaemia
What is a granuloma?
Focal aggregation of activated macrophages
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 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?
- Squamous cell carcinoma
- Small cell carcinoma
Which type of lung cancer tends to occur in non-smokers?
Adenocarcinoma
List some risk factors for lung cancer.
- Smoking
- Radiation
- Occupational and environmental hazards
- Radon
- Asbestos
- Air pollution
- Heavy metals
- Family history
- Pulmonary fibrosis
Describe the sequence of histological changes that results in lung cancer.
Metaplasia → Dysplasia → Carcinoma in situ → invasive carcinoma
What feature of squamous epithelium makes it vulnerable to undergoing malignant changes?
- It does not have cilia 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
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 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
- 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
