Lung Pathology Flashcards
What is Chronic Bronchitis?
Where in the airway is it?
What are the pathological features?
What is the aetiology?
Chronic inflammation of the Bronchus leading to
- excess mucus production
- dilatation of the airways
Usually 2nd to Tobacco + air pollution
What are the clinical features of chronic bronchitis?
Cough & sputum on most days for 3 months over 2 years
What are the histological findings in a lung with chronic bronchitis?
Dilatation of the airways
goblet cell hyperplasia and hypertrophy of mucous glands
What are complications of chronic bronchitis?
Recurrent infections
chronic hypoxia
Pulm HTN
What is Bronchiectasis?
Where in the airway is it?
What are the pathological features?
Airway dilatation and scarring (in the Bronchi)
Usually due to recurrent infections (CF!!)
Name 5 inflammatory causes of Bronchiectasis
Bronchiectasis required 2 components to form
- Chronic inflammation/ infection
- With inadequate clearence of secretions, airway obstruction or altered host defence
Inflammatory causes include
- Post-infectious (e.g. pertussis)
- Abnormal host defense: primary (hypogammaglobulinaemia) and secondary (chemotherapy, NG)
- Obstruction (extrinsic/intrinsic/middle lobe syn.)
- Post-inflammatory (aspiration)
- Secondary to bronchiolar disease (OB) and interstitial fibrosis (CFA, sarcoidosis)
- Systemic disease (connective tissue disorders)
- Asthma
Name 2 Congenital causes of Bronchiectasis
- Cystic fibrosis
- Primary ciliary dyskinesia
Others include:
Hypogammaglobulinema
Young’s syndrome = rhinosinusitis, azoospermia and bronchiectasis
What gene mutation causes Cystic Fibrosis?
Can be caused by many mutations, most commonly
1. AR mutation in CFTR gene (mostly F508del)
What is the pathogen most commonly causing infection in patients with cystic fibrosis?
Pseudomonas Aeruginosa
How does bronchiectsis clinically present?
Cough, purulent sputum, fever
On ausculation
- Crackles + rhonci
- Wheeze
- Bronchophony
What histological changes can be seen in Bronchiectasis?
Permanent fibrotic dilatation of the bronchi
What are histological chagnes seen in Asthma?
Smooth muscle cell hyperplasia
excess mucus (goblet cell hypertrophy) inflammation
Whorls of shed epithelium (Curschmann spirals), eosinophils, Charcot-Leyden crystals
What is emphysema?
Where in the airway is it?
What are the pathological features?
What is the aetiology?
Airspace enlargement and wall destruction in the Acinus
Usually due to
1. Smoking
2. consider alpha-1-antitrypsin deficiency in non-smokers
What histological changes can be seen in a patient with emphysema?
Loss of the alveolar parenchyma distal to the terminal bronchiole
Enlarged air space (turquiose on picture)
(+smooth muscle hyperplasia in COPD due to pulmonary hypertension)
What is instersitial lung disease?
Group of >200 diseases characterized by inflammation and fibrosis of the pulmonary connective tissue, accounting for 15% of respiratory disease burden.
Causes Restrictive lung disease!
What is a typcial clinical presentation of ILD (interstitial lung disease)?
Typical presentation
● Chronic shortness of breath (on exertion), progressive
● Fine end-inspiratory crackles
● Cyanosis, pulmonary HTN and cor pulmonale
- chronic, non-productive cough
What are the expected results of ILD on
1. spirometry
2. Imaging
3.
- Spirometry: Restrictive picture (reduced FEV1 and FVR but normal FEV1/FVC ratio i.e. >70%)
- Imaging: Fibrosis, in late stages CT can show ground glass/ honeycomb
What are the features of Cryptogenic Fibrosing Alveolitis / Idiopathic Pulmonary Fibrosis?
Epidemiology?
Aetiology?
Prognosis?
Most comon form of Fibrosing Interstitial lung disases (10:100.000/ year)
Usually affects Men 50-70 years
Cause unkonw
Usually progressive and resp.failure occurs within 3-7 years
What investigations are done for the diagnosis of Cryptogenic Fibrosing Alveolitis / Idiopathic Pulmonary Fibrosis?
What are the expected results?
Diagnosed after
1. exclusion of other causes for IDL
2. Evidence of the following on High Resolution CT or histology
Progressive patchy interstitial fibrosis with loss of normal lung architecture and honeycomb change, beginning at periphery of the lobule, usually sub-pleural
Hyperplasia of type II pneumocytes causing cyst formation–> honeycomb fibrosis.
What is Pneumoconiosis?
Type of fibrosing ILD caued by occupational inhalation of mineral dust or inorganic particles (e.g. coal miners)
–> usually affecting the upper lobe
(Asbestos is a form of pneumoconiosis usually affecting lower lobes)
In what two classes can Interstitial lung disease be classified (based on histological pattern).
Name 2 examples for each
- Fibrosing, e.g. Pneumoconiosis, idipathic pulmonary fibrosis and
- Granulomatous, e.g. sarcoidosis, extrinsic allergic alveolitis, other systemic vascultits
Name causes for the the developmen of granulomatous Lung disease (forma of interstitial lung disease with granulomas forming)
Infectious
1. TB
2. fungal (histoplasma, Cryptococcus, coccidioides, aspergillus, mucor) and others (pneumocystis, parasites)
Non-infectious granulomatous conditions include
1. sarcoid,
2. foreign body (aspiration or IVDU)
drugs or occupational lung disease.
What is the Pathophysiology of Extrinsivc allergic alveolitis?
A mix of type III and type IV hypersensitivity reactions
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.
Extrinsic allergic alveolitis has very similar presenations with different names, including: Hypersensitivity Pneumonitis/ Cryptogenic Organising Pneumonia / Bronchiolitis Obliterans Organising Pneumonia (BOOP)
What are histological presenations of Extrinsic allergic alveolitis?
polypoid plugs of loose connective tissue within alveoli/bronchioles
Non-caseating granuloma formation and organising pneumonia
Picture:
Poorly formed noncaseating (nonnecrotizing) granulomas are visible. The largest granuloma (arrow) has a core of large, pale epithelioid macrophages surrounded by lymphocytes and an outer layer of fibrous tissue. Smaller granulomas, multinucleated giant cells (blue overlay), and foamy histiocytes (examples indicated by arrowheads) are also visible.
How does a patient with acute Extrinsic allergic alveolitis present?
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.
What is a typical clinical presentaiton of chronic extrinsic allergic alveolitis?
Name some examples of diseases and their antigen (e.g. Farme’s lung –> hay)
Chronic presentation: Progressive persistent productive cough and SOB, finger clubbing and severe weight loss
- Pigeon Fancyer’s lung - (proteins in excreta/feathers
- Malt-workers lung (germinating barley – Aspergillus clavatus/fumigatus)
- Cheese washer’s lung (mouldy cheese – Aspergillus clavatus/penicillium casei).
What is a bronchopneumonia?
What tissues are involved and what organisms are usually causative?
pneumonia affecting the tissue around the bronchi and/or bronchioles (usually patchy)
Usually seen in low-virulence organisms (pneumococci, streptococci) affecting the frail or elderly
What is the disease progression of lobar pneumonias from day 1 to week 4?
Stages:
1.Consolidation
2. Red Hepatisation (neutrophilia) (lung tissues looks macroscopically like liver)
3. Grey Hepatisation (Fibrosis)
4. Resolution
What characteristics make a pneumonia atypical?
Quite generic features, usually referred to as pneumonias not caused by the common pathogens
Can present as
- slow onset
- non-productive, dry cough
- dyspnoea
- no/little findings on examination
- increased extra-pulomary features
–> interstitial pneumonai manifests as atypical pneumonia
What percentage of Lung malignancies are Small cell Lung cancers?
What cells do the originate from?
Make out aroune 20-25% of primary lung malignancies
Originate from neuroendcrine cells –> paraneoplastic syndromes are common (ADH, ACTH, Lambert Eaton)
How would small cell lung cancers present on histology?
Small, poorly differentiated “oat cells”
What is the prognosis for a patient with small cell lung cancer?
Usually poor prognosis due ot rapid progression + early metastasis (despite chemosensitivity) - 2/3 have metastasis on presentation
What are risk factors and common presentation in SCLC?
- Smoking (extremely rare in non-smokers)
- Usually centrally
What are common paraneoplastic syndromes associated with SCLC?
- ACTH –> cushings
- Lambert-eaton syndrome (–> like myastenia gravis but improves with repitition)
- SIADH
What two tissues types do Lung-cancers usually arise from?
What are 3 sub-types of cancers in each category?
- Non-small cell lung cancers: usually from connevtive tissues 85)
- Lung Adenocarcinoma
- Lung squamous cell caricinoma
- Large cell carinoma - Neuroendocrine cells
- small cell lung cancer
- (Others rarer: large cell neuroendocrine carcinoma, bronchio carcinoid tumour)
Where within the lung do most SCLC originate?
What is the main risk factor?
Usually centrally
+ very strong association with smoking (extremely rare in non-smokers)
What is the most common lung cancer in non-smokers?
Where in the lung does it usually arise and what are other risk factors?
Adenocarcinoma of the lung (is also the most common type of primary lung cancer)
Usually arise peripherally + metastasise early (but prognosis still better than oher types of lung cancer)
What are histological findings of an adenocarcinoma of the lung?
- Glandular tumor
- Mucin-producing cells (positive mucin staining)
- Lepidic adenocarcinoma: growth along alveolar walls (alveolar thickening)
What common mutations are found in adenocarcinomas of the lung?
- EGFR mutations
What are risk factors in the developmen of Squamous Call Carcinomas of the Lung?
Strong association with smoking
Male
Where in the lung do squamous cell carcinomas usually arise?
Usually arise proximally (usually from bronchus)
What genetic mutations are squamous cell lung cancers associated with?
p53/c-myc mutations
What histological findings would indicate squamous cell carcinoma of the lung?
Solid, epithelial tumor
Intercellular bridges (desmosomes)
Keratin pearls
What paraneoplastic syndrome is caused by squamous cell carcinomas of the lung?
Might produce Parathyroid hormone-related protein (PTHrP) –> hypercalcaemia
Where in the lung do large cell carcinomas usually arise?
What are histological findings?
Usually arise pripherally
Histology:
Undifferentiated
Large tumor cells
Poor prognosis
What is the definition of pulmonary hypertension?
An elevated pressure of >25mmHg (or 20mmHg MAP) in the pulmonary arteries
What different pathophysiological mechanisms can lead to pulmonary hypertension?
- Increase in pulmonary vascular resistance (e.g. hypoxic pulmonary vascoconstriction)
- Increase in pulmonary venous pressure (e.g. left heart failure)
- Increased pulomary blood flow
What is the leading cause of pulmonary oedema?
Left heart failure
What histological findings could be seen in pulmonary oedema?
acute – intra-alveolar fluid
Chronic: iron laden macrophages (“heart failure cells”).
Name 3 different causes of acute interstitial damage
- ITU hyperventilation
- ARDS
- HMD (hyaline membrane disease) in neonates (e.g. insufficient surfactant production in prems)
