Respiratory Pathology Flashcards
Roughly what percentage of deaths in England and Wales involve some respiratory pathology?
20.4%
What epithelium covers the conducting airways of the lungs?
Pseudostratified ciliated columnar mucous secreting epithelium
What is the epithelium of the alveoli?
Mostly flat type 1 pneumocytes (gas exchange) and some rounded type 2 pneumocytes (surfactant production)
What is the defines respiratory failure?
PaO2
What are the basic reasons for respiratory failure?
Due to defective:
1) Ventilation
2) Perfusion
3) Gas exchange
What is the difference between type 1 and type 2 respiratory failure?
Type 1 = paCO26.3kPa, hypercapnic respiratory drive
When does weight loss commonly occur in respiratory disease?
Catabolic state with chronic inflammation or tumours
What causes cyanosis?
Decreased oxygenation of haemoglobin
What does pleuritic pain indicate at a basic level?
Irritation of pleura
What kind of obstruction does stridor v wheeze indicate?
Stridor - proximal airway obstruction
Wheeze - distal airway obstruction
On auscultation of the lungs what abnormality do crackles indicate?
Resisted opening of airways
On auscultation what abnormality does a wheeze indicate?
Narrowed small airways
On auscultation what abnormality does bronchial breathing indicate?
Sound conduction through a solid lung
On auscultation what abnormality does pleural rub indicate?
Relative movement of inflamed visceral and parietal pleura
What does dullness on percussion indicate?
Lung consolidation or pleural effusion
What does hyperesonance on percussion indicate?
Pneumothorax or emphysema
Name 2 common lung infections?
1) Pneumonia
2) TB
Name 2 obstructive airway diseases?
1) Asthma
2) COPD
Name 3 interstitial lung diseases?
1) Adult respiratory distress syndrome
2) Fibrosing alveolitis
3) Sarcoidosis
Name 2 vascular lung diseases?
1) PE
2) Pulmonary hypertension
Name a pleural disease?
Pleural mesothelioma
Name a benign lung tumour?
Adenochondroma
What percentage of primary lung tumours are malignant carcinomas?
90%
What percentage of lung carcinomas are due to smoking?
80%
Incidence of lung cancer is second only to incidence of what cancer?
Breast cancer
The leading cause of cancer deaths in men and women in 2008 was what?
Lung cancer
What percentage of male lung carcinomas are attributable to asbestos exposure?
10%
Name 6 common risk factors for lung carcinoma?
1) Cigarettes
2) Asbestos, high level exposure with or without asbestosis
3) Lung fibrosis - including asbestosis and sarcoidosis
4) Radon
5) Chromates, nickel, tar, hematite, arsenic, mustard gas
What is asbestosis?
Pulmonary interstitial fibrosis caused by exposure to asbestos - asbestos bodies seen on light microscopy
What 4 respiratory conditions related to asbestos are prescribed occupational disease and sufferers receive industrial injuries disablement benefit?
1) Lung carcinoma with asbestosis
2) Asbestos related diffuse pleural fibrosis
3) Asbestos related silicosis
4) lung carcinoma in the absence of asbestosis if there is a history of over 5 years work in some high exposure occupations
What are carcinoid tumours?
Low grade neuroendocrine epithelial tumours
What are the 2 main classes of lung carcinomas?
1) Non small cell carcinoma
2) Small cell carcinoma
What are the 4 main types of non small cell carcinoma?
1) Squamous carcinoma
2) Adenocarcinoma
3) Large cell neuroendocrine carcinoma
4) Undifferentiated large cell carcinoma
What is common to all small cell carcinomas?
All are neuroendocrine
Are carcinomas usually exclusively small cell or non small cell?
No, multiple differentiation is common
What are more common, primary or secondary lung tumours?
Secondary tumours
What do secondary lung tumours typically look like on autopsy?
Multiple bilateral nodules, but can be solitary
What 3 things can help determine if a lung tumour is primary or secondary?
1) History - obvious if they have had a previous cancer
2) Morphology - some adenocarcinomas can be identified but not squamous
3) Antigen expression - immunocytochemistry is useful but not 100% reliable
What 2 Ag can be identified with immunocytochemistry in lung non-mucinous adenocarcinoma and small cell?
1) Cytokeratin
2) Thyroid transcription factor
What Ag can be identified with immunocytochemistry in colorectal mets?
1) Cytokeratin 20
What 2 Ags can be identified using immunocytochemistry in upper GI mets?
1) Cytokeratin 7
2) Cytokeratin 20
What Ag likely to identified using immunohistochemistry in breast mets?
Oestrogen receptor
What 3 Ags are identified using immunohistochemistry in melanoma mets?
1) S100
2) HMB45
3) MelanA
What is the typical location of lung carcinomas?
Most central, main or upper lobe bronchus (bronchogenic)
Traditionally which lung carcinoma tends to be more peripheral?
Adenocarcinoma
What are the 2 main histological features of squamous carcinoma?
1) Desmosomes link cells like epidermis
2) +/- keratinization
What is a common neoplastic syndrome associated with squamous carcinoma?
Hypercalcaemia due to parathyroid hormone related peptide
What is the basic pathological process of development of squamous carcinoma?
1) Squamous metaplasia - irritant such as smoke cause the epithelium to undergo reversible metaplastic change from pseudostratified columnar to stratified squamous type which may keratinize
2) Dysplasia - one metastatic cell undergoes irreversible genetic changes producing the first neoplastic cell
3) Developing dysplasia - neoplastic cell proliferates more successfully than metaplastic cells, the neoplastic clone replaces the metaplastic cells producing dysplasia (intra-epithelial neoplasia or carcinoma in situ)
4) Squamous carcinoma - neoplastic cells breach the basement membrane producing invasive squamous carcinoma
5) Invading neoplastic cells infiltrate lymphatic and blood vessels to produce metastases in lymph nodes and distant sites
Is squamous carcinoma more commonly central or peripheral in site?
More central
What are the main histological features of adenocarcinoma?
1) Glandular cells
2) Serous or mucous vacuoles in acinar, tubular, solid or papillary structures
Are adenocarcinomas more commonly peripheral or central?
Equally
What percentage of adenocarcinomas are found in smokers?
~80%
What percentage of squamous carcinomas are found in smokers?
~90%
What protein is expressed in many non-mucinous lung adenocarcinomas?
Thyroid transcription factor
What is bronchioalveolar carcinoma?
Spread of well differentiated mucinous or non-mucinous neoplastic cells on alveolar walls. Not invasive - adenocarcinoma in situ
What respiratory syndrome does bronchioalveolar carcinoma mimic?
Pneumonia
Is metastasis common in bronchioalveolar carcinoma?
Nodal and distal metastases are uncommon
What 3 proteins can be identified by immunocytochemistry due to neuroendocrine differentiation in lung and lung tumours?
1) Neural cell adhesion molecules
2) chromogranin,
3) synaptophysin
Name 4 neuroendocrine lung tumours, are all malignant?
1) Carcinoid
2) Atypical carcinoid
3) Large cell neuroendocrine carcinoma
4) Small cell carcinoma
yes but there is a spectrum of malignancy in neuroendocrine tumours
What is the growth pattern of typical carcinoid tumours?
Often grow into an occlude a bronchus
What are the histological features of carcinoid tumours? 3
1) Organoid, bland cells
2) No necrosis
3) >2 mitotic figures per 2 sqmm of a standard section
What syndrome are typical carcinoid tumours associated with?
Multiple endocrine neoplasia syndrome type 1
Are carcinoid tumours associated with smoking?
No
Are carcinoid tumours benign?
No - may invade lymphatic vessels and nodes but distant metastases to hilar nodes and distant sites are rare
There is a 95% 5 year survival
What percentage of lung carcinoids are atypical?
11%
What is the main difference between typical and atypical carcinoid tumours?
Atypical are more aggressive - metastases are common and 5 year survival reduced to 60%
What are the histological features of atypical carcinoid tumours?
1) Less organoid, more atypia
2) Nucleoli
3) Necrosis
4) 2-10 mitotic figures per 2sqmm
What is the main risk factor associated with large cell neuroendocrine carcinomas?
Smoking
How does the prognosis of large cell neuroendocrine tumours compare to that of other non-small cell lung carcinomas?
Similar or worse
What are the histological features of large cell neuroendocrine tumours?
1) Organoid architecture 2 Eoisinophilic granular cytoplasm 3) Antigen expression 4) Severe atypia 5) Nucleoli 6) Necrosis 7) >11 mitotic figures per 2 sqmm
What percentage of small cell carcinomas are found in smokers?
99%
Has small cell carcinoma in situ ever been identified?
No
What is a common finding on presentation with small cell carcinoma?
Small primary metastases - as they are rapidly progressive malignant tumours
What is a common histological finding in small cell carcinomas?
Neurosecretory granules with peptide hormones such as ACTH
What percentage of carcinomas have multiple differentiations?
~50%
What is needed for a carcinoma to be classified as a mixed non small cell lung carcinoma (mixed NSCLC)?
Need 10% of another component
eg. Adenocarcinoma
What is required for a classification of combined small cell carcinoma?
Any proportions of small cell carcinoma and non small cell carcinoma
What percentage of small cell carcinomas are actually combined small cell carcinomas?
~3%
What is the morphology of large cell carcinomas?
No specific squamous or glandular morphology
What percentage of large cell carcinomas express thyroid transcription factor?
~50%
Large cell carcinomas can be neuroendocrine, if so what do they commonly express?
CD56 and/or neurosecretory granule proteins
What are the 6 common paraneoplastic effects of lung carcinomas?
1) Cachexia
2) Skin - acanthosis nigricans, tylosis
3) Hypertrophic pulmonary osteoarthropathy (clubbing)
4) Coagulopathies - thrombophlebitis migrans
5) Encephalopathies, neuropathies and myopathies
6) Endocrine effects
Whiich neuropathy is commonly associated with small cell carcinoma (due to anti-neuromuscular junction auto-Abs)?
Lambert Eaton myasthenic syndrome
Gefitinib and erlotinib are new drugs used to treat lung carcinomas - they are ATP analogues which inhibit Epidermal growth factor receptor tyrosine kinase (EDFR-TK inhibitors) - can they be used in everyone?
No need activating mutation to be effective - sensitising mutations are present in 10% of non small cell lung cancers and are commoner in adenocarcinomas in non-smoking Asian women
What is the advantage of the new EDFR-TK inhibitors over standard chemo, are they curative?
Oral mediation can less toxic than standard cytotoxic chemotherapy
Not curative but stabilise progression until resistant mutations develop
Crizotinib is effective in about 90% of tumours with what mutation?
ALK-EML fusion gene
What is a chylothorax?
Lymph in interpleural space
What is empyema, what is it also known as?
Also known as pyothorax
Pus in the interpleural space
What are the 2 main types of causes of pleural effusion?
1) Inflammatory
2) Non inflammatory
Non inflammatory pleural effusion is caused by what, is it transudate or exudate?
Congestive cardiac failure - transudate
What is the difference between transudate and exudate?
Transudate - more watery fluid
Exudate - fluid containing cell bodies, cell materials and proteins
What is meant by pleurisy or pleuritis?
Inflammation of the pleura
What 5 conditions can cause pleuritis?
1) Collagen vascular disease
2) Pneumonia
3) TB
4) Lung infarct - usually secondary to pulmonary embolus
5) Lung tumour
How can asbestos affect the tumour? 3
Can cause:
1) Effusion
2) Fibrous plaques
3) Diffuse fibrosis
What is the name of a benign pleural tumour?
Fibroma
What is the most common pleural tumour?
Secondary adenocarcinoma - lung, breast
What is a primary pleural tumour called?
Mesothelioma
What exposure is related to mesothelioma?
Asbestos - long latent period
What are the histological features of malignant mesothelioma?
Mixed spindle cell and epitheloid cells - may be very fibrous (desmoplastic)
What are the steps in the progression of malignant mesothelioma? 4
1) Initial nodule and effusion
2) Later obliterates pleural cavity growing around the lung
3) Invades chest wall (pain) and lung
4) Nodal and distant metastases less common than with carcinomas
How do you differentiate malignant mesothelioma from adenocarcinoma?
Cellular antigen expression (immunocytochemistry)
What is the prognosis of malignant mesothelioma?
Uniformally fatal in, usually
What is the treatment for malignant mesothelioma?
Symptomatic treatment only
How does an early malignant mesothelioma appear and what can it cause?
Appears as small plaques on parietal pleura
May produce a significant pleural effusion
Where can fibrous pleural plaques commonly be seen, what are they caused by and do they have a physiological effect?
On the lower thoracic wall and diaphragmatic pleura, associated with low level asbestos exposure
No physiological effect, not pre-malignant
Why can a death certificate for a condition possibly involving asbestos exposure not be completed routinely?
Has to be referred to the coroner as possible death from occupation
What is the difference between a primary and secondary lung infection?
Primary - occurs in a previously health person
Secondary - occurs in a person with weakened defence
What 3 possible factors may be affected leading to a secondary lung infection?
1) Mucociliary escalator
2) Immunity
3) Pulmonary oedema
What 4 things may affect the mucocilliary escalator leading to a secondary lung infection?
1) Physical obstruction - tumour, foreign body
2) Cough reflex dampened
3) Ciliary dismotility - Kartagener’s syndrome
4) Mucus viscosity - cystic fibrosis
What 2 things can reduce macrophage function?
1) Hypoxia
2) Smoking
What primary infections is common in infants what does it lead to?
Bronchiolitis - follicular bronchiolitis, bronchiolitis obliterans
Can resolve or develop into bronchopneumonia
What are the structural findings in pneumonia?
Inflammatory exudate in alveoli and distal small airways - consolidation
In what 4 ways can pneumonia be classified?
1) Clinical - primary or secondary
2) Aetiological - bacterial, viral, fungal
3) Anatomical - lobar pneumonia or bronchopneumonia
4) Reaction - purulent, fibrinous
Is bronchopneumonia primary or secondary?
Secondary - usually to compromised defences, often caused by low virulence bacteria or occasionally fungi
What kind of pneumonia tends to heal with scarring?
Bronchopneumonia
Does lobar pneumonia tend to be primary or seconday, caused by what?
Primary - 90% virulent strep pneumonia
Lobar pneumonia typically affects which group?
Males 20-50 years
What pathogen commonly causes lobar pneumonia in the elderly, diabetics and alcoholics?
Klebsiella pneumoniae
What is seen in atypical pneumonias (occur in the non-immunosuppressed)?
Interstitial lymphocytes, plasma cells, macrophages
Intra-alveolar fibrinous cell-poor exudate
Diffuse alveolar damage
What are the 3 kinds of non-infective pneumonias?
1) Aspiration pneumonia - secondary infection often with mixed anaerobes produces abscesses
2) Lipid pneumonia - endogenous (retention pneumonitis), exogenous (aspiration)
3) Cryptogenic organising pneumonia and bronchiolitis obliterans organising pneumonia
What pathogen causes pulmonary TB?
Mycobacterium TB
What 2 risk factors are associated with TB?
1) Socioeconomic deprivation
2) Immunosuppression - including AIDS
What are the steps in TB infection?
1) Primary infection - asymptomatic, ghon complex in peripheral lung and hilar nodes, usually resolves
2) Reactivation - usually atypical
3) Resolution or progression - empyema, pneumonia, military or more limited spread to other organs - bone, kidney
4) Scarring- fibrous calcified scar
What are the histological finding in pulmonary TB?
Granulomas with multinucleated Langhan’s giant cells and caseous necrosis
Atypical mycobacteria tend to cause TB in which patients, why is this worse than mycobacterium TB?
Tend to infect lungs with pre-existing pathology such as COPD and are more resistant to treatment than M tuberculosis
What are the 3 types of pulmonary vasculitis?
1) Necrotising granulomatous vasculitis
2) Goodpasture’s syndrome
3) Microvascular damage - ARDS and DAD, SLE
What is bronchiectasis?
Permanent dilation of bronchi and bronchioles caused by destruction of the muscle and elastic tissue
What causes bronchiectasis?
Results from chronic necrotizing infection
What are the 3 main symptoms of bronchiectasis?
1) Cough
2) Fever
3) Foul smelling sputum
What are 4 pre-disposing conditions to bronchiectasis?
1) CF
2) Primary ciliary dyskinesia, Kartagener syndrome
3) Bronchial obstruction: tumour, foreign body
4) Autoimmune diseases - lupus, rheumatoid arthritis, IBD, GVHD
What are the 4 possible complications of bronchiectasis?
1) Pneumonia
2) Septicaemia
3) Metastatic infection
4) Amyloid
Is bronchiectasis an example of diffuse or localised obstructive pulmonary disease?
Localised
Other than bronchiectasis, give 3 other localised obstructive pulmonary diseases?
1) Tumour or foreign body
2) Distal alveolar collapse (total) or over expansion (valvular obstruction)
3) Distal retention pneumonitis and bronchopneumonia
Give 2 diffuse obstructive pulmonary diseases?
COPD, Asthma
What is COPD?
Combination of chronic bronchitis and emphysema
What is chronic bronchitis?
Cough and sputum for 3 months in each of 2 consecutive years
What are the causes of chronic bronchitis?
Chronic irritation and smoking and air pollution
What is emphysema?
Abnormal permanent dilation of airspaces distal to the terminal bronchiole with destruction of the airspace wall, without obvious fibrosis (vs. overinflation in which there is no airspace wall destruction)
What are the 3 classfications of emphysema?
1) Centrilobar -most common, due to coal dust and smoking
2) Panlobular - due to alpha1-antitrypsin deficiency
3) Paraseptal - upper lobe subpleural bullae - adjacent to fibrosis, pneumothorax if rupture
What is the main symptom of emphysema?
Dyspnoea - progressive and worsening
What is the stereotype of a COPD patient with predominant bronchitis vs. predominant emphysema?
Predominant bronchitis - blue bloater
Predominant emphysema - pink puffer
Is cor pulmonale more common in COPD patients with predominant bronchitis or emphysema?
Predominant chronic bronchitis
What would be the differences seen on a CXR of a COPD pt with predominant bronchitis compared to emphysema?
Predominant bronchitis - Prominent vessels, large heart
Predominant emphysema - small heart, hyper inflated lung
What would be the differences in age affected, dyspnoea symptoms, cough and frequency of infections in COPD with predominant bronchitis compared to predominant emphysema?
Predominant bronchitis - 40-45, mild dyspnoea late in disease, cough early in disease, commonly infected
Predominant emphysema- 50-75, severe dyspnoea early, cough late in disease, infections rare
What exposure is COPD commonly related too (except smoking)?
Coal mining
What are the 4 clinicopathological classifications of asthma?
1) Atopic
2) Non-atopic
3) Aspirin - induced
4) Allergic bronchopulmonary aspergillosis
What happens to the structure of the lungs in asthma?
1) Mucosal inflammation and oedema
2) Hypertrophic mucous glands and mucus plugs in bronchi
3) Hyperinflated lungs
Are interstitial lung diseases restrictive or obstructive?
Restrictive
What is interstitial lung disease?
Increased tissue in alveolar capillary wall - inflammation and fibrosis, decreased lung compliance and increased gas diffusion distance
Acute interstitial disease causes what?
Adult respiratory distress syndrome
What happens to the alveolar wall in acute interstitial disease?
Exudate and death of type 1 pneumocytes form hyaline membranes lining alveoli followed by type 2 pneumocyte hyperplasia
Give 4 examples of chronic interstitial lung diseases?
1) Idiopathic pulmonary fibrosis
2) Many pneumoconiosis (dust disease)
3) Sarcoidosis
4) Collagen vascular diseases-associated lung diseases
What are the 4 main clinical signs and symptoms in chronic interstitial lung diseases?
1) Dyspnoea increasing from months to years
2) Clubbing
3) Fine crackles
4) Dry cough
What is idiopathic pulmonary fibrosis also known as, what is the prognosis and what bit of the lung is affected?
Cyrptogenic fibrosing alveolitis
5 year mortality 57%
Sub-pleural, lower lobes affected first and most severely
How does the pleural surface appear in idiopathic pulmonary fibrosis?
Bosselated (cobblestone) pleural surface due to contraction of interstitial fibrous tissue, accentuates lobular architecture
What is sarcoidosis?
Non caseating perilyphatic pulmonary granulomas then fibrosis, hilar lymph nodes usually involved, other organs may be affected
What 2 biochemical findings are seen in sarcoidosis?
1) Hypercalcaemia
2) Elevated serum ACE
Sarcoidosis typically affects which group?
Young adult females
What are pneumoconiosis?
Diseases of the lung due to inhalation of mineral dusts, organic dusts, fumes and vapours
Pneumoconiosis used to be common in which workers?
Coal workers
What is silicosis?
Lung fibrosis due to inhalation of silica (sand and stone dust) which kills phagocytosing macrophages
Silicosis can lead to possible reactivation of which infection?
TB
Silicosis leads to increased risk of what normally fatal disease?
Lung carcinoma
What is asbestosis?
Inhalation of asbestos leading to interstitial fibrosis
What is hypersensitivity pneumonitis?
Extrinsic allergic alveolitis - its a type 3 hypersensitivity reaction to organic dusts, get peribronchiolar inflammation with poorly formed non caseating granulomas extends alveolar walls - repeated episodes lead to interstitial fibrosis
What is hypersensitivity pneumonitis known as in laymens terms?
Pigeon fanciers lung or farmer’s lung
What are the 3 major occupational lung diseases?
1) COPD in coal miners
2) Asbestos associated lung cancer
3) Asbestos associated malignant mesothelioma
