Histopathology 12 - Respiratory pathology Flashcards
What are the causes of pulmonary hypertension?
What causes diffuse alveolar damage? How does diffuse alveolar damage appear on CXR?
Caused by: a) ARDS in adults and b) hyaline membrane disease of the newborn in neonates
Firm and expanded lungs
What are the acute features of the airway in asthma?
Acute bronchospasm
Acute mucosal oedema
Inflammation
What are the chronic features of the airway in asthma?
Muscular hypertrophy
Airway narrowing
Mucus plugging
What are the features of COPD?
Chronic bronchitis and emphysema
Describe the features of chronic bronchitis
Chronic cough productive of sputum
Most days for at least 3 months over at least 2 consecutive years
How does chronic hypoxia affect the heart?
Pulmonary hypertension —> right heart failure
What is emphysema?
Permanent loss of the alveolar parenchyma distal to the terminal bronchiole
What is the genetic association of emphysema?
Alpha 1 anti-trypsin
Recall the pathophysiology of emphysema
Smoking causes inflammation
Neutrophil and macrophage involvement
Proteases recruited
Breakdown of epithelium
What does lung bullous rupture cause?
Pneumothorax
What is bronchiectasis?
Permanent abnormal dilatation of bronchi with inflammation and fibrosis into adjacent parenchyma
Recall the complications of bronchiectasis
Haemoptysis
Pulmonary HTN
RHF
Amyloidosis secondary to chronic inflammation
Which condition has the strongest association with bronchiectasis?
Cystic fibrosis
What is bronchopneumonia?
Inflammation centred around airway
Where does bronchopneumonia often affect?
Lower lobes
Which type of pneumonia has become much rarer since ABx have been in use?
Lobar pneumonia
What is empyema?
Infected pleural effusion
Which type of pneumonia is most likely to cause interstitial inflammation?
Atypical pneumonias
What are the most common lung tumours?
Epithelial tumours - non small cell and small cell
What are the 3 subtypes of non-small cell lung cancer?
Adenocarcinoma
Squamous cell carcinoma
Large cell carcinoma
Which 2 types of lung cancer are most associated with smoking?
Squamous cell
Small cell
Where is squamous cell carcinoma most likely to develop in the lung?
Centrally
Where do adenocarcinomas typically develop?
Peripherally
Which mutations are smokers most likely to develop in adenocarcinomas?
K ras
p53
Which mutations are non-smokers most likely to develop in adenocarcinomas?
EGFR
Which type of lung cancer is assoiated with the most paraneoplastic syndromes?
Small cell
Which mutations are most likely to develop in squamous cell carcinomas?
They’re not - it’s the adenocarcinomas that tend to get the mutations
What type of lung cancer is the most common in the UK?
Squamous cell carcinoma
List the obstructive lung diseases
- chornic bronchitis
- bronchiectasis
- asthma
- emphysema
- small airway disease/ bronchiolitis
What are the causes of bronchiectasis?
Inflammatory
o Post-infectious (e.g. pertussis) o Abnormal host defense 1º (hypogammaglobulinaemia) and 2º (chemotherapy, NG)
o Obstruction (extrinsic/intrinsic/middle lobe syn.)
o Post-inflammatory (aspiration)
o Secondary to bronchiolar disease (bronchiolitis obliterans) and interstitial fibrosis (CFA, sarcoidosis)
o Systemic disease (connective tissue disorders)
o Asthma
● Congenital
o Cystic fibrosis o Primary ciliary dyskinesia o Hypogammaglobulinema o Young’s syndrome = rhinosinusitis, azoospermia and bronchiectasis
Which infectious pathogen is most likely to cause bronchiectasis?
Staph aureus
Which obstructive resp disease causes haemptysis?
Bronchiectasis
WHat are the features of restrictive lung disease?
- decreased CO diffusion capacity
- decreased lung volume
- decreased lung compliance
Typical presentation of interstitial lung disease
- fine end inspiratory crackles
- chronic shortness of breath
- cyanosis, pulmonary HTN and cor pulmonale
What is the CT appearance of interstitial lung disease?
Honeycombing
What can you split up the causes of interstitial lung disease into?
1. fibrosing
a. Cryptogenic Fibrosing Alveolitis/ Idiopathic pulmonary fibrosis
b. Pneumoconiosis
c. Cryptogenic organizing pneumonia
d. Associated with connective tissue disease
e. Drug-induced
f. Radiation pneumonitis
2. granulomatous
- sarcoid
- extrinsic allergic alveolitis
- associated with vasculitides - wegener’s, churg strauss, microscopic polyangiitis
Histology of idiopathic pulmonary fibrosis
Usual Interstitial Pneumonia
o Progressive patchy interstitial fibrosis with loss of normal lung architecture and
honeycomb change, beginning at periphery of the lobule, usually sub-pleural
o Hyperplasia of type II pneumocytes causing cyst formation – honeycomb fibrosis
Tx of idiopathic pulmonary fibrosis
steroids, cyclophosphamide, azathioprine, pirfenidone (not especially effective)
Where does pneumoconiosis affect the lungs vs. asbestosis?
Pneumocniosis- upper lobes
Asbestosis- lower lobes
Pathophsyiology of extrinsic allergic alevolitis
Group of immune-mediated lung disorders caused by intense/prolonged exposure to inhaled ORGANIC antigens → widespread ALVEOLAR inflammation (cf asthma = airway inflammation).
Extrinsic allergic alveolitis is typically an occupational lung disease and can be acute or chronic.
Presetation of EAA
inhalation of antigenic dust in SENSITISED individual -→ systemic symptoms (fever, chills, chest pain, SOB, cough) within hours of exposure, usually settle by following day.
Progresses to chronic EAA.
Types of EAA
e.g. Farmers lung (mouldy hay/grain/silage – Saccharopolyspora rectivirgula)
Pigeon fancier’s lung (proteins in excreta/feathers)
Humidifier’s lung (heated water reservoirs – thermactinomyces spp.),
Malt-workers lung (germinating barley – Aspergillus clavatus/fumigatus)
Cheese washer’s lung (mouldy cheese – Aspergillus clavatus/penicillium casei).
Type of antigen in pneumoconiosis vs EAA
pneumoconiosis- inorganic antigen (mineral dust or coal)
eaa- organic antigens
What are the 3 patterns of pneumonia?
- bronchopneumonia- inflammation around the airways
- lobar pneumonia - entire lobe is affected. basc a more severe version; incidence is lower now
- atypical - affects the INTERSTITIUM. interstitial pneumonitis; without any intra-alevolar cells
Histology and Stages of lobar pneumonia
Fibrinosuppurative consolidation.
Stages:
- Consolidation;
- RedHepatisation (neutrophilia);
- Grey Hepatisation (Fibrosis);
- Resolution
Male female preponderance of squamous cell carcinoma vs adenocarcinoma
squamous cell carcinoma- more common in males
adenocarcinoma- more common in females
Where in the lungs do small cell carcinomas occur?
Centrally, proximal bronchi (similar to squamous)
Which cells du small cell caricnomas arise from?
neuroendocrine cells
paraneoplastic syndromes of small cell carcinoma
- etcopic acth secretion
- lambert-eaton- immune system attacks the neuromuscular junctions
- cerebellar degeneration
between squamous cell carcinoma and adenocarcinoma which one is more aggressive?
squamous: metastasises late. less responsive to chemo.
adeno: metastasises early. more responsive to chemo.
*one positive, one negative for each one*
Mutations in small cell carcinoma
p53 and rb1
how quickly does small cell carcinoma metastasise?
quite quickly
poor prognosis despite being chemosensitive
where does small cell carcinoma metastaisse to?
bone
adrenal
liver
brain
histology of large cell carcinoma
Poorly differentiated malignant epithelial tumour – large cells, large nuclei, prominent nucleoli.
Histology – no evidence of glandular or squamous differentiation. Poor prognosis.
**basic poorly differentiated**
what paraneoplastic syndrome is this: flushing, diarrhoea, bronchoconstriction?
carcinoid syndrome - serotonin release
which mutation, if present, allows targeted treatment?
EGFR mutation- present usually in adenocarcinoma
target with tyrosine kinase inhibitor
What % of pulmonry bed needs to be occluded to cause shock and death from pulmonary emboli?
60%
What is a saddle embolus?
Blocks pulmonary trunk
what are heart failure cells?
iron laden macrophages found in pulmonary oedema
What enzyme does alpha 1 antitrypsin deficiency affect?
neutrophil elastase
Signet ring sign positive?
Bronchiectasis
Which cancer is associated with oat shaped cells on biopsy?
Small cell lung cancer
Diagnostic investigation for pulmonary fibrosis?
High resolution chest CT
**changes not seen on x-ray or standard CT**
Intracellular desmosomes/ bridges (prickles) - classic
squamous cell carcinoma
