Resp Lectures 15+16 lung pathology Flashcards
(101 cards)
1
Q
What makes up the conducting airways?
A
Trachea
Left & right main bronchi
Segmental & smaller bronchi
Bronchioles, terminal bronchioles
2
Q
What constitutes gas exchange
A
Respiratory bronchioles
Alveolar ducts
Alveolar sacs
Alveoli
3
Q
Histology of conducting airways
A
Pseudostratified cilliated columnar mucus secreting epithelium
4
Q
Histology of Alveoli
A
Mostly flat Type I pneumocytes (gas exchange) & some rounded Type II pneumocytes (surfactant production)
5
Q
Respiratory failure caused by defective….what
A
Ventilation
Perfusion
Gas exchange
6
Q
Type 1 resp failure
A
(paCO2
7
Q
Type 2 resp failure
A
(paCO2>6.3kPa)
Hypercapnic respiratory drive
8
Q
Sputum Resp Signs and symptoms
A
Mucoid, purulent, haemoptysis
9
Q
Cough Resp Signs and symptoms
A
Reflex response to irritation
10
Q
Stridor Resp Signs and symptoms
A
Proximal airway obstruction
11
Q
Wheeze Resp Signs and symptoms
A
Distal airway obstruction
12
Q
Pleuritic pain Resp Signs and symptoms
A
Pleural irritation
13
Q
Auscultation resp exam: Crackles, Wheeze, bronchial breathing, pleural rub
A
Crackles – Resisted opening of small airways
Wheeze – narrowed small airways
Bronchial breathing – Sound conduction through solid lung
Pleural rub – Relative movement of inflamed visceral & parietal pleura
14
Q
Percussion resp exam: Dull, hyper resonant
A
Dull – Lung consolidation or pleural effusion
Hyperesonant – Pneumothorax or emphysema
15
Q
Primary tumours: Benign and malignant Lung Neoplasm
A
Benign: Adenochondroma (glandular/cartilage involvement)
Malignant: Carcinoma (epithelial)
16
Q
Lung carcinoma risk factors
A
Asbestosis and silicosis
cigarette smoking
17
Q
Asbestos
A
Amphiboles - blue asbestos (crocidolite) – the most dangerous brown asbestos (amosite) Serpentines - white asbestos (chrysotile)- the least dangerous
18
Q
Asbestosis
A
High level exposure produces pulmonary interstitial fibrosis
19
Q
How can asbestosis bodies be seen?
A
By light microscopy, their Fibres are coated with mucopolysacharide & ferric iron salts
20
Q
Asbestosis and lung carcinomas
A
Higher incidence of all types of lung carcinoma associated with high level exposure to asbestos
21
Q
Lung carcinoma with asbestosis, asbestos related diffuse pleural fibrosis or silicosis
A
Prescribed occupational disease (Not with mixed dust pneumoconiosis (coal workers pneumoconiosis) )
22
Q
Lung carcinoma in the absence of asbestosis
A
Prescribed industrial disease
23
Q
Malignant primary lung tumours: Non small cell small-cell Carcinoid (Others: lymphomas, sarcomas, carcinosarcomas)
A
-Non-Small cell carcinoma: (squamous carcinoma, adenocarcinoma, large cell neuroendocrine carcinoma,
undifferentiated large cell carcinoma)
- Small-cell carcinoma: All are Neuroendocrine
- Carcinoid: Low grade neuroendocrine epithelial tumours
24
Q
Secondary lung tumours
A
Secondary tumours - commonest tumours in the lung usually from a known primary but may be the presenting feature of a distant primary tumour
Typically multiple bilateral nodules but can be solitary
May be difficult to determine whether primary or secondary
25
How to know if primary or secondary
```
History
Morphology
some adenocarcinomas, but not squamous
Antigen expression
Immunocytochemistry is useful but not 100% reliable
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26
Lung non-mucinous adenocarcinoma & small cell
| Immunocytochemistry
cytokeratin & thyroid transcription factor positive
27
Colorectal Immunocytochemistry
cytokeratin 7 negative & cytokeratin 20 positive
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Upper G.I Tract Immunocytochemistry
cytokeratin 7 positive & cytokeratin 20 positive
29
Breast Immunocytochemistry
may be oestrogen receptor positive
30
Melanoma Immunocytochemistry
S100, HMB45, MelanA positive & cytokeratin negative
31
Lung Carcinoma usual sites
Most central, main or upper lobe bronchus (bronchogenic)
Adenocarcinoma more peripheral
32
Squamous carcinoma
desmosomes link cells like epidermis (‘epidermoid’)
+/- keratinization
~90% in smokers
central > peripheral
hypercalcaemia due to parathyroid hormone related peptide
33
what epithelium lines the bronchus
Pseudostratified columnar epithelium with ciliated and mucus-secreting cells
34
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)
35
Dysplasia
One metaplastic cell undergoes irreversible genetic changes (a series of sequential somatic mutations of oncogenes & anti-oncogenes) producing the first neoplastic cell
36
Developing dysplasia
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
Squamous carcinoma
Neoplastic cells breach the basement membrane producing invasive squamous carcinoma
Invading neoplastic cells infiltrate lymphatic & blood vessels --> produce metastases in lymph nodes & distant sites
38
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
39
Bronchioloalveolar 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
40
Neuroendocrine differentiation in lung & lung tumours
Look for neuroendocrine cell proteins by immunocytochemistry:
Neural cell adhesion molecule (CD56)
Neural secretory granule proteins (chromogranin, synaptophysin)
Neural secretory granule by electron microscopy
41
spectrum of malignancy of neuroendocrine tumours
carcinoid, atypical carcinoid, large cell neuroendocrine carcinoma and small cell carcinoma
42
Typical carcinoid tumours
Often grow and occlude a bronchus
| Organoid, bland cells, no necrosis,
43
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
44
Large cell neuroendocrine carcinomas
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
Small Cell Carcinoma
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
Carcinomas with multiple differentiation
```
Mixed NSCLC (contains 2 different types of cells)
-Adenosquamous
```
Combined small cell carcinoma
-Any proportions of small cell carcinoma & NSCLC
~3% of small cell carcinoma, depends on extent of sampling
47
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
Effects of Lung carcinomas
Cachexia
| Clubbing
49
Effects of Lung carcinomas of skin
Acanthosis nigricans, tylosis
50
Effects of Lung carcinomas on blood
Coagulopathies - thrombophebitis migrans
51
Effects of Lung carcinomas Neurology
Encephalomyelitis, neuropathies & myopathies
| Lambert Eaton myasthenic syndrome due to anti-neuromuscular junction autoantibodies in small cell carcinoma
52
Effects of Lung carcinomas Endocrinologically
- Parathyroid hormone-related peptide from squamous cell carcinoma causing hypercalcaemia
- ACTH and antidiuretic hormone from small cell carcinoma
- 5-hydroxytryptamine - carcinoid (uncommon)
53
EGFR-TK inhibitors
Gefitinib (Iressa) and erlotinib (Tarceva) are ATP analogues that inhibit EGFR-TK if activating mutations are present
(Sensitising mutations present in 10% of non-small cell lung cancers and are commoner in adenocarcinomas in non-smoking Asian women?????)
54
ALK (Anaplastic lymphoma kinase) gene re-arrangements
Variable break point inversion on short arm of chromosome 2 fuses ALK and EML (echinoderm microtubule like protein) genes activating ALK tyrosine kinase.
Present in about 10% of lung adenocarcinomas
Non-smoking, Asian, women again
Independent of EGFR or RAS mutations
Crizotinib
- ATP analog inhibits ALK, ROS1, c-Met (Hepatocyte Growth Factor receptor /HGFR) tyrosine kinases.
- Temporary control – no progress or regress
55
Pleural diseases
```
Pneumothorax- air
-Tension pneumothorax
Pleural effusion
-transudate or exudate
Haemothorax- blood
Chylothorax- lymph
Empyema- Pus
```
56
Causes of Pleural effusion
```
Inflammatory:
-Serous/fibrinous –exudate
-Due to inflammation/infection in adjacent lung
Non inflammatory:
-Congestive Cardiac Failure – transudate
```
57
Non-neoplastic Pleura diseases
inflammation (pleurisy, pleuritis)
- collagen vascular diseases
- pneumonia, tuberculosis
- lung infarct, usually secondary to pulmonary embolus
- lung tumour
asbestos
-effusion, fibrous plaques, diffuse fibrosis
58
Pleural Tumours Benign and malignant
Benign - rare
-fibroma
Malignant - common
- Usually secondary adenocarcinoma - lung, breast
- Primary malignant mesothelioma is rarer
59
Malignant Mesothelioma
Occupational, paraoccupational or environmental contamination
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)
60
Early malignant Mesothelioma
Small plaques on the parietal pleura
Difficult to image & biopsy
May produce a significant pleural effusion
61
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
62
What does a Weak fluorodeoxyglucose uptake in mediastinal lymph nodes mean?
probably reactive rather than neoplastic
63
Why secondary infections can occur more often?
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
64
Cause of Acute Bronchitis
Viral (RSV), H. influenzae, Strep. pneumoniae
Croup
Exacerbations of COAD
65
Causes of Bronchiolitis
Primary acute in infants, RSV, rare, resolve or develop bronchopneumonia
Follicular bronchiolitis
Bronchiolitis obliterans
66
Pneumonia
Inflammatory exudate in alveoli & distal small airways - consolidation
67
Classifying Pneumonia (Clinical, aetiological, anatomical, reaction)
```
Classifications:
Clinical - primary or secondary
Aetiological - Bacterial, viral, fungal
Anatomical - lobar pneumonia or bronchopneumonia
Reaction - purulent, fibrinous
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68
Bronchopneumonia
```
Secondary - compromised defences
Often low virulence bacteria or occasionally fungi
Common
Patchy
Bronchocentric
Resolve or heal with scarring
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69
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
70
Atypical pneumonias (not immunosuppressed)
Non-immunosuppressed
- Viral - flu, varicella, RSV, rhino, adeno, measles
- Mycoplasma pneumoniae - Mild, chronic, fibrosis
- Chlamydia (psittacosis), Coxiella burnetti (Q-fever)
- Legionella pneumophilla - Systemic, 10- 20% fatal
Severity mild to fatal
Intersitial lymphocytes, plasma cells, macrophges
Intra-alveolar fibrinous cell-poor exudate
Diffuse alveolar damage (DAD)
71
Atypical pneumonias (immunosuppressed)
Lymphomas, medication, AIDS
Opportunistic infections by low virulence or non-virulent organisms
-Fungi - candida, aspergillus, Pnumocystis carinii
-Viruses - CMV, HSV, measles
72
Non-infective pneumonias (Aspiration, lipid, cryptogenic)
Aspiration pneumonia
-Secondary infection often with mixed anaerobes produces abscesses
Lipid pneumonia
- Endogenous – retention pneumonitis
- Exogenous – aspiration
Cryptogenic organising pneumonia & bronchiolitis obliterans organising pneumonia (COP & BOOP)
73
Pulmonary tuberculosis
```
Mycobacterium tuberculosis
Lung is the commonest site of infection
Associations
Socioeconomic deprivation
Immunosuppression - including AIDS
```
74
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.
Can lead to empyema, pneumonia, miliary
75
Pulmonary Vasculitis features
Necrotising granulomatous vasculitis - Wegener’s granulomatosis (kidneys & nose, elevated serum ANCA)
Churg-Strauss syndrome (eosinophilia & asthma)
Goodpasture’s syndrome - Anti-glomerular basement membrane antibody, Intra-alveolar haemorrhage & glomerulonephritis
Microvascular damage - ARDS & DAD, SLE
76
Obstruction- types of Emboli
Thromboemboli
- Common
- Deep leg vein thrombosis - risk factors & prevention
- Size determines symptoms - sudden death, SOB, chest pain, pulmonary hypertension, right ventricular failure
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Fat emboli - fat & marrow from bone fractures
Air
Amniotic fluid
Tumour
Foreign bodies
```
77
Obstructive pulmonary diseases (Localised)
- 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)
Can be resected
78
Bronchiectasis
Site: Bronchus/bronchioles
Cause: Infections (…)
Signs/ symptoms: Cough, fever, copious amounts of foul smelling sputum
- Permanent dilation of bronchi and bronchioles caused by destruction of the muscle and elastic tissue
- Results from chronic necrotizing infection
79
Predisposing conditions for Bronchiectasis
- Cystic fibrosis
- Primary ciliary dyskinesia, Kartagener syndrome
- Bronchial obstruction: tumour, foreign body
- Lupus, rheumatoid arthritis, inflammatory bowel disease, ---GVHD
80
Obstructive pulmonary diseases (Diffuse)
Diffuse
- Chronic obstructive pulmonary disease (COPD) aka chronic obstructive airways disease.
- Asthma
81
What is COPD
A combination of chronic bronchitis & emphysema
82
What is chronic bronchitis
Cough & sputum for 3 months in each of 2 consecutive years
Site: Bronchus
Cause : Chronic irritation, Smoking & air pollution, Middle aged & old
Pathology: Mucus gland hyperplasia and hypersecretion, secondary infection by low virulence bacteria, chronic inflammation
Chronic inflammation of small airways of the lung causes wall weakness & destruction thus centrilobular emphysema
83
What is Emphysema
Emphysema: Abnormal permanent dilation of airspaces distal to the terminal bronchiole, with destruction of airspace wall, without obvious fibrosis
84
Emphysema classification:
Centrilobar
Panlobar
Paraseptal
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
85
Blue bloater
Chronic Bronchitis
- Excessive mucus production with airway obstruction resulting from hyperplasia of mucus-producing glands, goblet cell metaplasia, and chronic inflammation around bronchi.
- body responds to the increased obstruction by decreasing ventilation and increasing cardiac output. There is a dreadful ventilation to perfusion mismatch leading to hypoxemia and polycythemia.
- Hypercapnia
- Cyanotic appearance
86
Pink Puffer
Emphysema
- Gradual destruction of the pulmonary capillary bed and thus decreased inability to oxygenate the blood.
- body then has to compensate by hyperventilation
- develop muscle wasting and weight loss
87
Prescribed Occupational disease
Chronic bronchitis &/ Emphysema
88
Asthma
Chronic inflammatory disorder of the airways
Mucosal inflammation & oedema
Hypertrophic mucous glands & mucus plugs in bronchi
Hyperinflated lungs
Clinicopathological classification
-Atopic , non-atopic, aspirin-induced, allergic bronchopulmonary aspergillosis (ABPA)
89
Atopic Asthma Pathology
Type I hypersensitivity reaction
- Allergen - dust, pollen, animal products
- 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
90
Interstitial Lung disease
```
Usually diffuse and chronic
Diseases of pulmonary connective tissue
(Mainly alveolar walls)
Restrictive rather than obstructive lung disease
Causes often unknown
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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
91
Acute interstitial 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
92
Chronic Interstitial Disease
Dyspnoea increasing for months to years
Clubbing, fine crackles, dry cough
Common end-stage fibrosed “honeycomb lung”
Examples:
- idiopathic pulmonary fibrosis,
- many pneumoconioses (dust diseases)
- sarcoidosis,
- collagen vascular diseases-associated lung diseases
93
Idiopathic pulmonary fibrosis (cobblestone look)
cryptogenic fibrosing alveolitis
Sub-pleural, lower lobes affected first & most severely
Histology - usual interstitial pneumonia (UIP)
-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
94
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
95
Pneumoconioses“The dust diseases”
```
Inhaled dusts
-inert
-fibrogenic
-allergenic
-oncogenic
lung carcinoma & pleural mesothelioma
```
96
Coal workers’ pneumoconiosis (CWP)
Anthracosis
Silicosis
Asbestosis
```
Anthracosis:
Simple (macular) CWP
Nodular CWP
Progressive massive fibrosis
COPD (‘chronic bronchitis & emphysema’) if >20yrs underground mining
```
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
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
Increased risk of lung cancer with asbestosis and with high asbestos exposure but no fibrosis
97
Hypersensitivity pnumonitis
| 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
98
Cystic Fibrosis
Mutation in CFTR gene
Autosomal recessive inheritance
affects fluid secretion in exocrine glands and the epithelial lining of the respiratory, gastrointestinal and reproductive organs
99
Cystic fibrosis Lung
Bronchioles distended with mucus
Hyperplasia mucus secreting glands
Multiple repeated infections
Severe chronic bronchitis and bronchiectasis
100
Cystic fibrosis Pancreas
Exocrine gland ducts plugged by mucus
Atrophy and fibrosis of gland
Impaired fat absorption, enzyme secretion, vitamin deficiencies ( pancreatic insufficiency)
101
Cystic fibrosis: Other organs
Small bowel: mucus plugging - meconium ileus
Liver: plugging of bile cannaliculi – cirrhosis
Salivary glands: Similar to pancreas: artophy and fibrosis
95% of males are infertile
