Pathology of the respiratory system Flashcards
1
Q
What kind of epithelium do conducting airways have?
A
Pseudostratified columnar
2
Q
What epithilium would you find in alveoli?
A
Mostly flat Type I pneumocytes (gas exchange) & some rounded Type II pneumocytes (surfactant production)
3
Q
What is respiratory failure?
A
Having a PaO2 of less than 8.0kPa
4
Q
What is type I respiratory failure?
A
- (paCO2<6.3kPa)
- Hypoxic respiratory drive
5
Q
What is type II respiratory failure?
A
- (paCO2>6.3kPa)
- Hypercapnic respiratory drive
6
Q
What is the cause of cough?
A
Reflex response to irritation
7
Q
What is the cause of stridor?
A
Proximal airway obstruction
8
Q
What is the cause of wheeze?
A
Distal airway obstruction
9
Q
What is the cause of pleuritic pain?
A
Pleural irritation
10
Q
What is the cause of dyspnoea?
A
Impaired alveolar gas exchange?
11
Q
What is the cause of cyanosis?
A
Decreased oxygenation of haemoglobin.
12
Q
What is the cause of weight loss in respiratory illness?
A
Catabolic state with chronic inflammation or tumours.
13
Q
What is the cause of crackles on ascultation?
A
Resisted opening of small airways.
14
Q
What is the cause if brochial breathing on auscultation?
A
Sound conduction through solid lung.
15
Q
What is the cause if pleural rub on auscultation?
A
Relative movement of inflamed visceral & parietal pleura.
16
Q
What is the cause of dull percussion?
A
Lung consolidation or pleural effusion.
17
Q
What is the cause of hyperesonant percussion?
A
Pneumothorax or emphysema.
18
Q
Give an example of a primary benign lung tumour.
A
Adenochondroma - rare.
19
Q
What percentage of lung cancer deaths in the UK are due to smoking?
A
80%
20
Q
What are the 2 and 5 year survival rates for lung cancer in Yorkshire?
A
10% and 6%
21
Q
What are the risk factors for lung cancinoma?
A
Tobacco 80%
Secondary smoke 10% - 30%
Asbestos 10% (usually male)
Lung fibrosis - including asbestosis and silicosis
Radon (Miners, igneous rocks, gas from ground accumulates in homes)
Cromates, nickle, tar, haematite, arsenic, mustart gas
22
Q
What is the body’s initial response to high levels of asbestos?
A
Pulmobary interstitial fibrosis - asbestosis.
23
Q
What is the main association between asbestos and lung carcinomas?
A
Higher incidence of all types of lung carcinoma associated with high level exposure to asbestos
24
Q
What are the hypotheses regarding asbestos and lung carcinoma?
A
– Fibrosis – no increased risk without asbestosis
– Fibre burden - dose related, some risk at all exposure level
25
What is the epidemiological evidence for the link between asbestos and lung carcinoma?
•For
–Increased risk in workers exposed to asbestos
–Increased risk in the absence of “small opacities” on CXR in asbestos exposed workers
•Against
–No increased risk in low level exposed workers or Canadian asbestos mining towns inhabitants with no occupational exposure
26
What are the various types of non-small cell carcinoma (85% of primaries)?
squamous carcinoma 52%
adenocarcinoma 13%
large cell neuroendocrine carcinoma
undifferentiated large cell carcinoma
27
What type of tumours are small cell carcinomas?
Neuroendocrine
28
What kind of tumours are carcinoid?
Low grade neuroendocine epithelial tumours
29
What other primary malignant tumours are possible?
Lymphomas, sarcomas, carcinosarcomas.
30
What are the commonest tumours of the lung?
Metastases
31
What are the gross features of lung metastases?
Typically multiple bilateral nodules but can be solitary
32
How can you tell the difference between a primary and a secondary tumour of the lung?
* History
* Morphology
– some adenocarcinomas, but not squamous
•Antigen expression
–Immunocytochemistry is useful but not 100% reliable
33
What are the features of squamous cell carcinoma?
* desmosomes link cells like epidermis (‘epidermoid’)
* +/- keratinization
* ~90% in smokers
* central \> peripheral
* hypercalcaemia due to parathyroid hormone related peptide
34
What kind of epithelium is bronchial epithelium?
The normal bronchus is lined by pseudostratified columnar epithelium with ciliated and mucus-secreting cells.
35
What is squamous metaplasia?
Irritants such as smoke cause the epithelium to undergo a reversible metaplastic change from pseudostratified columnar to stratified squamous type which may keratinize (like skin)
36
What is dysplasia?
One metaplastic cell undergoes irreversible genetic changes (a series of sequential somatic mutations of oncogenes & anti-oncogenes) producing the first neoplastic cell.
The neoplastic cell proliferates more sucessfully than the metaplastic cells
The neoplastic clone relaces the metaplastic cells producing dysplasia ( intraepithelial neoplasia or carcinoma-in-situ)
37
What are the features of adenocarcinoma?
* glandular cells, serous or +/- mucus vacuoles, in acinar, tubular, solid or papillary structures
* central = peripheral
* ~80% in smokers
* Thyroid transcription factor (TTF) is expressed in many non-mucinous lung adenocarcinomas
38
What is brochioalveolar carcinoma?
* Spread of well differentiated mucinous or non-mucinous neoplastic cells on alveolar walls
* Not invasive - “adenocarcinoma in situ”
* Mimics pneumonia
* Uncommon nodal & distant metastases
39
What is the name of the neuroendocrine cells normally found in normal lung mucosa?
Kulchitsky cells
40
What is the first stage in the development of neuroendocrine tumours of the lungs?
Intraepithelial neuroendocrine cell hyperplasia & carcinoid tumourlets (
41
What type of neuroendocrine tumours are known?
Carcinoid, atypical carcinoid, large cell neuroendocrine carcinoma and small cell carcinoma
42
What are the features of typical carcinoid tumours?
* Often grow into and occlude a bronchus
* Organoid, bland cells, no necrosis,
* Associated with multiple endocrine neoplasia syndrome type 1
* Not associated with smoking
* Not “benign” may invade lymphatic vessels and nodes but rare distant metastases 6-9% to hilar nodes, less to distant sites, 95% 5yr survival
43
What are the features of atypical carcinoid tumours?
* 11% of lung carcinoids
* Less organoid, more atypia, nucleoli - may be focal atypia in an otherwise typical carcinoid
* Necrosis, 2-10 mitotic figure per 2sqmm
* More aggressive than typical carcinoids
– 70% metastasise
– 60% 5yr survival
44
What are the features of large cell neuroendocrine tumours?
•Neuroendocrine morphology
– organoid architecture, eosinophilic granular cytoplasm
– antigen expression
* Severe atypia, nucleoli, necrosis, \>11 mitotic figures per 2sqmm
* Prognosis similar to or worse than other non-small cell lung carcinomas
* Associated with smoking
45
What are the features of small cell carcinomas?
* Rapidly progressive malignant tumours
* Neurosecretory granules with peptide hormones such as ACTH
* May have small primary with metastases before presentation
* ~99% in smokers
* No “small cell carcinoma in situ” identified
46
What are the features of carcinomas with multiple differentiation?
* Common
* ~50% , depends on extent of sampling
* Mixed NSCLC
–Need 10% of a component for classification
–Adenosquamous
•Combined small cell carcinoma
–Any proportions of small cell carcinoma & NSCLC
–~3% of small cell carcinoma, depends on extent of sampling
47
What are the features of large cell carcinomas?
* No specific squamous or glandular morphology
* ~50% express thyroid transcription factor
* Can be neuroendocrine
–Express CD56 &/or neurosecretory granule proteins (synaptophysin, chromogranin)
48
What are the possible paraneoplastic effects of lung carcinomas?
* Cachexia
* Skin - acanthosis nigricans, tylosis
* Hypertrophic pulmonary osteoarthropathy (clubbing)
* Coagulopathies - thrombophebitis migrans
* Encephalomyelitis, neuropathies & myopathies
–Lambert Eaton myasthenic syndrome due to anti-neuromuscular junction autoantibodies in small cell carcinoma
•Endocrine effects
–Parathyroid hormone-related peptide from squamous cell carcinoma causing hypercalcaemia
–ACTH and antidiuretic hormone from small cell carcinoma
–5-hydroxytryptamine - carcinoid (uncommon)
49
What is the mechanism of action of gefitinib and erlotinib?
- ATP analogues that inhibit EGFR-TK if activating mutations are present.
- Inhibition of EGFR TK mediated protein phosphorylation and activation of the mitotic cycle
- Sensitising mutations present in 10% of non-small cell lung cancers and are commoner in adenocarcinomas in non-smoking Asian women
- Not curative but stabilises progression until resistance mutations develop
50
What is ALK?
Anaplastic lymphoma kinase - tyrosine kinase
51
What percentage of adenocarcinomas have an ALK gene rearrangement?
10%
52
What are the features of crizotiniib?
* ATP analog inhibits ALK, ROS1, c-Met (Hepatocyte Growth Factor receptor /HGFR) tyrosine kinases.
* Temporary control – no progress or regress
* Effective in about 90% of tumours with ALK-EML fusion gene
53
What is pleural effusion?
Transudate or exudate collecting in the pleural cavity.
54
What is chylothorax?
Lymph collecting in the pleural cavity.
55
What is empyema (pyothorax)?
Pus collecting in the pleural cavity.
56
What are the possible causes of pleural effusion?
Inflammatory:
Serous/fibrinous –exudate
Due to inflammation/infection in adjacent lung
Non inflammatory:
Congestive Cardiac Failure – transudate
57
What tests may be performed on the fluid taken from pleural effusion?
- LDH, pH, Glucose of fluid can be measured to suggest a diagnosis
- Cytology used to assess the presence of malignant or inflammatory cells
58
What non-neoplastic diseases may cause pleural pathology?
–inflammation (pleurisy, pleuritis)
* collagen vascular diseases
* pneumonia, tuberculosis
* lung infarct, usually secondary to pulmonary embolus
* lung tumour
–asbestos
•effusion, fibrous plaques, diffuse fibrosis
59
Give a name to a benign pleural tumour.
Fibroma - rare
60
What are the two most common malignant pleural tumours?
–Usually secondary adenocarcinoma - lung, breast
–Primary malignant mesothelioma is rarer
•2401 cases in 2007 in the UK
61
What percentage of mesothelioma is associated with asbestos exposure?
\>90% - epecially brown or blue
62
What is the latent period between asbestos exposure and the development of mesothelioma?
15 to 60+
63
What is the progression of mesothelioma?
* Initial nodule and effusion. Later obliterates pleural cavity growing around the lung
* Invades chest wall (pain) & lung
* Nodal and distant and metastases less common than with carcinomas
* Mixed spindle cell and epithelioid cells. May be very fibrous (desmoplastic)
64
How is diagnosis of mesothelioma performed and what is the prognosis?
* Differential diagnosis from reactive mesothelial cells in inflamed pleura can be very difficult
* Differentiate from adenocarcinoma by
* cellular antigen expression (immunocytochemistry on cytology or biopsy)
* Symptomatic treatment
* Uniformly fatal in, usually
65
What are the macroscopic features of early malignant mesothelioma?
* Small plaques on the parietal pleura
* Difficult to image & biopsy
* May produce a significant pleural effusion
66
What are fibrous pleural plaques?
* On the lower thoracic wall & diaphragmatic parietal pleura
* Associated with low level asbestos exposure
* No physiological effect
* Not premalignant
* Seen on radiographs, a marker of possible asbestos exposure
67
What is the difference between primary and secondary respirartory infections?
* Primary - Previously healthy
* Secondary - Weakened defence
–Mucocilliary escalator
* Physical obstruction – tumour, foreign body
* Cough reflex
* Cilliary dysmotility – Kartagener’s syndrome
* Mucus viscosity – cystic fibrosis
–Immunity
* Hypogammaglobulinaemia , lymphomas, immunosuppressive drugs, AIDS
* Macrophage function – smoking, hypoxia
– Pulmonary oedema
68
What is the most common cause of bronchiolitis?
Respiratory syncytial virus
69
What are the possible causes of acute bronchitis?
–Viral (RSV), H. influenzae, Strep. pneumoniae
–Croup
–Exacerbations of COAD
70
What are the pathological features of pneumonia?
•Inflammatory exudate in alveoli & distal small airways - consolidation
71
What are the features of bronchopnuemonia?
* Secondary - compromised defences
* Often low virulence bacteria or occasionally fungi
* Common
* Patchy
* Bronchocentric
* Resolve or heal with scarring
72
What are the key features of lobar pneumonia?
* Primary - typically male 20 to 50 years
* 90% - virulent Strep pneumoniae
* Uncommon
* Confluent segments, whole lobe or lobes with overlying pleuritis
* Congestion, red then grey hepatisation, resolution without scarring
* Klebsiella pneumoniae - elderly, diabetic, alcoholic
73
What is the common progression of pulmonary tuberculosis?
* Primary infection - Asymptomatic, Ghon complex in peripheral lung & hilar nodes, usually resolves
* Reactivation - usually apical
* Resolution or progression - empyema, pneumonia, miliary or more limited spread to other organs - bone, kidney
* Scarring - fibrous calcified scar
74
What is the pathophysiology of pulmonary tuberculosis?
* Granulomas with multinucleated Langhans’ giant cells & caseous necrosis
* Usually few bacilli but intense immune reaction causes tissue damage
* Type IV hypersensitivity to tuberculin - Heaf & Mantoux tests
* Atypical mycobacteria –tend to infect lungs with preexisting pathology such as COPD & are more resistant to treatment than M tuberculosis.
75
What are the potential pathologies behind vascular pulmonary disease?
* Vessel wall inflammation - vasculitis
* Obstruction of flow
* Haemodynamic disturbances
76
What is necrotising granulomatous vasculitis?
- Wegener’s granulomatosis (kidneys & nose, elevated serum ANCA)
- Churg-Strauss syndrome (eosinophilia & asthma)
77
What is Goodpasture's syndrome?
Anti-glomerular basement membrane antibody, Intra-alveolar haemorrhage & glomerulonephritis
78
Which diseases can cause microvascular damage to the lungs?
ARDS & DAD, SLE
79
What is usually the cause of a pulmonary embolism?
Deep leg vein thrombosis
80
What are the other possible causes of PE?
* Fat emboli - fat & marrow from bone fractures
* Air
* Amniotic fluid
* Tumour
* Foreign bodies
81
Give examples of localised obstructive pulmonary diseases.
–Tumour or foreign body
–Distal alveolar collapse (total) or over expansion (valvular obstruction)
–Distal retention pneumonitis (endogenous lipid pneumonia) and bronchopneumonia
–Distal bronchiectasis (bronchial dilatation)
82
What is bronchiectasis?
Permanent dilation of bronchi and bronchioles caused by destruction of the muscle and elastic tissue
Results from chronic necrotizing infection
83
What are the signs/symptoms of bronchiectasis?
Cough, fever, copious amounts of foul smelling sputum
84
What are risk factors for bronchiectasis?
–Cystic fibrosis
–Primary ciliary dyskinesia, Kartagener syndrome
–Bronchial obstruction: tumour, foreign body
–Lupus, rheumatoid arthritis, inflammatory bowel disease, GVHD
\>
85
What are the complications of bronchiectasis?
Pneumonia, septicaemia, metastatic infection, amyloid
86
What are the two main diffuse obstructive pulmonary diseases?
–Chronic obstructive pulmonary disease (COPD) aka chronic obstructive airways disease.
–Asthma
87
What is COPD?
A combination of chronic bronchitis & emphysema
88
What are the features of chronic bronchitis?
- cough & sputum for 3 months in each of 2 consecutive years
–Site: Bronchus
–Cause : Chronic irritation
Smoking & air pollution
–Middle aged & old
1 in 20 of \>65yr consult g.p. per year
89
What is the pathology of chronic bronchitis?
Mucus gland hyperplasia and hypersecretion, secondary infection by low virulence bacteria, chronic inflammation
90
How does chronic bronchitis cause emphysema?
Chronic inflammation of small airways of the lung causes wall weakness & destruction thus centrilobular emphysema
91
What is emphysema?
Abnormal permanent dilation of airspaces distal to the terminal bronchiole, with destruction of airspace wall, without obvious fibrosis
92
What are the classifications of emphysema?
–Centrilobular (centiacinar)
Coal dust, smoking
–Panlobular (panacinar)
\>80% a1 antitrypsin deficient (rare, autosomal dominant) , severest in lower lobe bases
–Paraseptal (distal acinar)
Upper lobe subpleural bullae adjacent to fibrosis. Pneumothorax if rupture
93
What are the symptoms of emphysema?
Dyspnoea: progressive and worsening
94
Under what conditions are chronic bronchitis and emphysema considered occupational diseases?
* UK prescribed occupational disease in coal miners since 1992
* Chronic bronchitis &/or emphysema
* \>20 years underground work
* Compensation depends on degree of disability & smoking history
* No CXR or history of dust exposure needed
95
What is asthma?
Chronic inflammatory disorder of the airways with paroxysmal bronchospasm
96
What are the symptoms of asthma?
–Wheeze
–Cough
–Variable bronchoconstriction that is at least partially reversible
97
What is the pathology of asthma?
* Mucosal inflammation & oedema
* Hypertrophic mucous glands & mucus plugs in bronchi
* Hyperinflated lungs
* Clinicopathological classification
–Atopic , non-atopic, aspirin-induced, allergic bronchpulmonary aspergillosis (ABPA)
98
What is the pathology of atopic asthma?
•Type I hypersensitivity reaction
–Allergen - dust, pollen, animal products
–Cold, exercise, reparatory infections
–Many different cell types and inflammatory mediators involved
–Degranulation of IgE bearing mast cells
* histamine initiated bronchoconstriction & mucus production obstructing air flow
* eosinophil chemotaxis
* Persistent or irreversible changes
–bronchiolar wall smooth muscle hypertrophy
–mucus gland hyperplasia
–respiratory bronchiolitis leading to centrilobular emphysema
99
What is the epidemiology of atopic asthma?
* Children & young adults
* Common
–33.9% UK children 12-14 years with “wheeze” in 2002
–1 in 10 UK children diagnosed with asthma
–590,000 teenagers
•9 – 15% adult onset asthma is occupational
–The commonest occupational lung disease
100
What is usually the cause of interstitial lung disease?
•Diseases of pulmonary connective tissue
–Mainly alveolar walls
101
Is intersitial lung disease restictive or obstructive?
Restrictive
102
What are the pathological features of interstitial lung disease?
•Increased tissue in alveolar-capillary wall
–Inflammation & fibrosis
–Limited morpholgical patterns that differ with site and with time in any individual but with many causes & clinical associations
* Decreased lung compliance
* Increased gas diffusion distance
103
What are the features of acute intersitial disease?
•Diffuse alveolar damage – exudate & death of type I pneumocytes form hyaline membranes lining alveoli followed by type II pneumocyte hyperplasia. Histologically acute interstitial pneumonia
–Adult respiratory distress syndrome (shock lung) - shock, trauma, infections, smoke, toxic gases, oxygen, paraquat, narcotics, radiation, aspiration, DIC
104
What are the clinical features of chronic interstitial lung diseases?
* Dyspnoea increasing for months to years
* Clubbing, fine crackles, dry cough
* Interstitial fibrosis and chronic inflammation with varying radiological and histological patterns
* Common end-stage fibrosed “honeycomb lung”
105
Give examples of chronic interstitial lung disease.
–idiopathic pulmonary fibrosis,
–many pneumoconioses (dust diseases)
–sarcoidosis,
–collagen vascular diseases-associated lung diseases
106
What are the features of idiopathic pulmonary fibrosis?
* aka cryptogenic fibrosing alveolitis
* 5000 new cases per year in UK, middle aged & elderly
* 3 & 5 year mortality 43% & 57% (expected 12% & 19%)
* Sub-pleural, lower lobes affected first & most severely
107
What is the histology of idiopathic pulmonary fibrosis?
–Interstitial chronic inflammation & variably mature fibrous tissue
–Adjacent normal alveolar walls
–Similar pattern of fibrosis in collagen vascular disease associated interstitial lung disease and in asbestosis
108
What is sarcoidosis?
* Non-caseating perilymphatic pulmonary granulomas, then fibrosis
* Hilar nodes usually involved
* Other organs may be affected- skin,heart, brain
* Hypercalcaemia & elevated serum ACE
* Typically young adult females, aetiology unknown
109
What are pneumoconioses?
* Originally defined as the non neoplastic lung diseases due to inhalation of mineral dusts in the workplace
* Now also includes organic dusts, fumes and vapours
110
How small do particulates have to be to reach the alveoli?
111
What are the possible features of coal workers' pneumoconiosis?
* Anthracosis
* Simple (macular) CWP
* Nodular CWP
* Progressive massive fibrosis
* COPD (‘chronic bronchitis & emphysema’) if \>20yrs underground mining
112
What are the features of silicosis?
* Silica - sand & stone dust
* Kills phagocytosing macrophages
* Fibrosis & fibrous silicotic nodules, also in nodes
* Possible reactivation of tuberculosis
* Increased risk of lung carcinoma - lung carcinoma with silicosis is a UK “prescribed occupational disease”
* Mixed dust pneumoconiosis – silica with other dusts
113
What are the features of asbestosis?
* High level exposure produces interstitial fibrosis, in a usual interstitial pneumonia pattern
* Histologically like idiopathic pulmonary fibrosis or collagen vascular disease associated pulmonary fibrosis but asbestos bodies are identifiable in tissue sections
* Difficult to diagnose with certainty but incidence of 1000 cases per year likely in UK
* Increased risk of lung cancer with asbestosis and with high asbestos exposure but no fibrosis
114
What are the features of hypersensitivity pneumonitis?
* aka extrinsic allergic alveolitis
* Type III hypersensitivity reaction organic dusts
–farmers’ lung - actinomycetes in hay
–pigeon fanciers’ lung - pigeon antigens
* Peribronchiolar inflammation with poorly formed non-caseating granulomas extends alveolar walls
* Repeated episodes lead to interstitial fibrosis
