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Flashcards in Respiratory Pathology Deck (100):

What proportion of children are diagnosed with asthma?

1 in 10 UK children


What percentage of the UK population have COPD?



What type of epithelium lines the conducting airways?

Pseudostratified cilliated columnar mucus secreting epithelium


How do you define respiratory failure?



What is type I respiratory failure?



What is type II respiratory failure?

Hypercapnic respiratory drive


What is a cough?

Reflex response to irritation


What causes stridor?

Proximal airway obstruction


What causes wheeze?

Distal airway obstruction


What causes pleuritic pain?

Pleural irritation


What causes cyanosis?

Decreased oxygenation of haemoglobin


What can we find out using percussion?

Dull – Lung consolidation or pleural effusion

Hyperesonant – Pneumothorax or emphysema


On auscultation, what do crackles mean?

Resisted opening of small airways


On auscultation, what does wheeze mean?

narrowed small airways


On auscultation, what does bronchial breathing mean?

Sound conduction through solid lung


On auscultation, what does pleural rub mean?

Relative movement of inflamed visceral & parietal pleura


Which vascular diseases are associated with the lungs?

pulmonary embolism,
pulmonary hypertension


What is a benign lung tumour called?



What type of tumour makes up 90% of lung tumours?



What percentage of lung cancer is due to smoking?



What are the risk factors for lung cancer?

cigarettes (80%)
secondary cigarette smoke - 10-30% increase

asbestos, high level exposure, with or without asbestosis
In UK about 2000 cases per year, 10% of male lung carcinomas

lung fibrosis – including asbestosis and silicosis

Schneeberg mines (in 1879 the first description of occupational lung cancer) , igneous rocks - Aberdeen

chromates, nickel, tar, hematite, arsenic, mustard gas


What is asbestos?

Fibrous metal silicates, 5-100μm x φ 0.25−0.5μm

Amphiboles - blue asbestos (crocidolite) – the most dangerous

brown asbestos (amosite)

Serpentines - white asbestos (chrysotile)- the least dangerous

High level exposure produces pulmonary interstitial fibrosis

Asbestos bodies seen by light microscopy
Fibres coated with mucopolysacharide & ferric iron salts


What are the two types of carcinoma?

non-small cell carcinoma (85%)
squamous carcinoma 52%
adenocarcinoma 13%
large cell neuroendocrine carcinoma
undifferentiated large cell carcinoma

small cell carcinoma (15%)
all are neuroendocrine

Multiple differentiation is common


What are carcinoid tumours?

Low grade neuroendocine epithelial tumours


How is it determined if a lung tumour is primary or secondary?

some adenocarcinomas, but not squamous
Antigen expression
Immunocytochemistry is useful but not 100% reliable


Where are most lung carcinomas?

Most central, main or upper lobe bronchus (bronchogenic)

Adenocarcinoma more peripheral
scar cancers or cancer with a fibrous (desmoplastic) reaction?


Key points on Squamous carcinoma

desmosomes link cells like epidermis (‘epidermoid’)
+/- keratinization
~90% in smokers
central > peripheral
hypercalcaemia due to parathyroid hormone related peptide


What type of epithelium are the bronchi lined by?

The normal bronchus is lined by pseudostratified columnar epithelium with ciliated and mucus-secreting cells


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)


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


How does dysplasia develop?

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)


What are the paraneoplastic effects of lung carcinomas?


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)


What is classed as T1 stage lung malignancy?



What is classed as T2 stage lung malignancy?


>2cm to carina

lobar atelectasis or obstructive pneumonia to hilus


What is classed as T3 stage lung malignancy?



What is classed as T4 stage lung malignancy?

tumour in carina

invasion - heart, great vessels, trachea, oesophagus, spine

nodules - in other ipsilateral lobes


What are "epidermal growth factor receptor tyrosine kinase inhibitors"?

Gefitinib (Iressa) and erlotinib (Tarceva) are ATP analogues that inhibit EGFR-TK if activating mutations are present

Oral medication, less toxic than standard cytotoxic chemotherapy

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


What is crizotinib?

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 FDA approval Aug 2011 for late stage (local advanced or metastatic) NSCLC
>$100,000 per patient per year

UK approval expected


What are the different types of pleural cavity problems called?

Pneumothorax = air
tension pneumothorax
Pleural effusion (hydrothorax)
- transudate or exudate
Haemothorax = blood
Chylothorax = lymph
Empyema (prothorax) = pus


What are the main causes of pleural effusion?

- Serous/fibrinous –exudate
- Due to inflammation/infection in adjacent lung
Non inflammatory:
- Congestive Cardiac Failure – transudate
LDH, pH, Glucose of fluid can be measured to suggest a diagnosis
Cytology used to assess the presence of malignant or inflammatory cells


What are the main causes of pleural effusion?

- Serous/fibrinous –exudate
- Due to inflammation/infection in adjacent lung

Non inflammatory:
- Congestive Cardiac Failure – transudate
LDH, pH, Glucose of fluid can be measured to suggest a diagnosis
Cytology used to assess the presence of malignant or inflammatory cells


What problems affect the pleura?

Non-neoplastic disease:

inflammation (pleurisy, pleuritis)
- collagen vascular diseases
- pneumonia, tuberculosis
- lung infarct, usually secondary to pulmonary embolus
- lung tumour

- effusion, fibrous plaques, diffuse fibrosis


Pleural tumours?

Benign - rare
Malignant - common
Usually secondary adenocarcinoma - lung, breast
Primary malignant mesothelioma is rarer
2401 cases in 2007 in the UK


What are the features of malignant mesothelioma?

2401 cases in 2007 in UK
Expected to increase to 3000 by 2020
>90% associated with asbestos exposure, blue (especially) or brown most hazardous
Exposure may be low level
Long latent period of 15 to 60+ years from exposure before the mesothelioma develops


What is the epidemiology of malignant mesothelioma?

2401 cases in 2007 in UK
Expected to increase to 3000 by 2020
>90% associated with asbestos exposure, blue (especially) or brown most hazardous
Exposure may be low level
Long latent period of 15 to 60+ years from exposure before the mesothelioma develops


What are the features of malignant mesothelioma?

Occupational, paraoccupational or environmental contamination (South African mines, Robert’s asbestos factory in Canal Road, Armlet)

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)


How is malignant mesothelioma detected and treated?

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


What are the early signs of malignant mesothelioma?

Small plaques on the parietal pleura

Difficult to image & biopsy

May produce a significant pleural effusion


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


What are causes of acute bronchitis?

Viral (RSV), H. influenzae, Strep. pneumoniae
Exacerbations of COAD


What are the features of pneumonia?

Inflammatory exudate in alveoli & distal small airways - consolidation
Clinical - primary or secondary
Aetiological - Bacterial, viral, fungal
Anatomical - lobar pneumonia or bronchopneumonia
Reaction - purulent, fibrinous


What are the classifications of pneumonia?

Clinical - primary or secondary
Aetiological - Bacterial, viral, fungal
Anatomical - lobar pneumonia or bronchopneumonia
Reaction - purulent, fibrinous

Inflammatory exudate in alveoli & distal small airways - consolidation



Secondary - compromised defences
Often low virulence bacteria or occasionally fungi
Resolve or heal with scarring


What are the features of lobar pneumonia?

Primary - typically male 20 to 50 years
90% - virulent Strep pneumoniae
Confluent segments, whole lobe or lobes with overlying pleuritis
Congestion, red then grey hepatisation, resolution without scarring
Klebsiella pneumoniae - elderly, diabetic, alcoholic


What about non-immunosuppressed atypical pneumonias?

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)


What about immunosuppressed atypical pneumonias?

Lymphomas, medication, AIDS
Opportunistic infections by low virulence or non-virulent organisms
Fungi - candida, aspergillus, Pnumocystis carinii
Viruses - CMV, HSV, measles


What about non-infective pneumonias?

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)


What bacteria causes tuberculosis?

Mycobacterium tuberculosis


What things increase risk of tuberculosis?

Socioeconomic deprivation
Immunosuppression - including AIDS


What is the epidemiology of tuberculosis?

One third of the world’s population infected (that’s not the same as having the disease)
50% fatality if untreated
3,000,000 deaths per year worldwide


What is the progression of 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


Microbiology in 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.


What are the features of pulmonary vascular diseases?

Vessel wall inflammation - vasculitis
Obstruction of flow
Haemodynamic disturbances


What is pulmonary vasculitis?


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


What about emboli?

- Common
- Deep leg vein thrombosis - risk factors & prevention
- Size determines symptoms - sudden death, SOB, chest pain, pulmonary hypertension, right ventricular failure

Fat emboli - fat & marrow from bone fractures
Amniotic fluid
Foreign bodies


What are obstructive pulmonary diseases?

Localised or diffuse obstruction of air flow

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)


What is Bronchiectasis?

Permanent dilation of bronchi and bronchioles caused by destruction of the muscle and elastic tissue
Results from chronic necrotizing infection
Rare ( for now…..)


What are the signs of bronchiectasis?

Signs/ symptoms: Cough, fever, copious amounts of foul smelling sputum

Site: Bronchus/bronchioles
Cause: Infections (…)


What are the causes of bronchiectasis?

Infections(…) – predisposing conditions:
Cystic fibrosis
Primary ciliary dyskinesia, Kartagener syndrome
Bronchial obstruction: tumour, foreign body
Lupus, rheumatoid arthritis, inflammatory bowel disease, GVHD


What are the causes of bronchiectasis?

Infections(…) – predisposing conditions:
Cystic fibrosis
Primary ciliary dyskinesia, Kartagener syndrome
Bronchial obstruction: tumour, foreign body
Lupus, rheumatoid arthritis, inflammatory bowel disease, GVHD


What are some possible complications of bronchiectasis?

pneumonia, septicaemia, metastatic infection, amyloid


What are diffuse obstructive pulmonary diseases?

Chronic obstructive pulmonary disease (COPD) aka chronic obstructive airways disease.


What is COPD in its simplest form?

A combination of chronic bronchitis & emphysema


What is chronic bronchitis?

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


What is the pathology behind chronic bronchitis?

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


What is emphysema

Emphysema: Abnormal permanent dilation of airspaces distal to the terminal bronchiole, with destruction of airspace wall, without obvious fibrosis

(vs overinflation, in which there is no airspace wall destruction)


What are the classifications of emphysema?

Centrilobular (centiacinar) Coal dust, smoking

Panlobular (panacinar) - >80% α1 antitrypsin deficient (rare, autosomal dominant) , severest in lower lobe bases

Paraseptal (distal acinar) - Upper lobe subpleural bullae adjacent to fibrosis. Pneumothorax if rupture


What are the typical features of COPD with predominant bronchitis?

younger (40-45)
mild dyspnea late in disease
early cough with copious sputum
infections common
repeated respiratory insufficiency
common cor pulmonate
xray - prominent vessels, large heart
stereotype - blue bloater


What are the typical features of COPD with predominant emphysema?

older (50-75)
severe, early dyspnea
late cough with scanty sputum
infections rare
terminal respiratory insufficiency
rare, terminal cor pulmonale
xray - small heart, hyper inflated lungs
stereotype - pink puffer


What is asthma?

Chronic inflammatory disorder of the airways
Paroxysmal bronchospasm
Variable bronchoconstriction that is at least partially reversible


How many asthma patients are there in the UK?

5.2 million


What are the signs 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)


What is the pathology behind 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


What are some persistent or irreversible changes associated with asthma?

bronchiolar wall smooth muscle hypertrophy
mucus gland hyperplasia
respiratory bronchiolitis leading to centrilobular emphysema


Facts about interstitial lung disease?

Very heterogenous group
Usually diffuse and chronic
Diseases of pulmonary connective tissue
Mainly alveolar walls
Restrictive rather than obstructive lung disease
Causes often unknown


What is the pathology of interstitial lung disease?

?Increased tissue in alveolar-capillary wall
- Inflammation & fibrosis
- Limited morphological patterns that differ with site and with time in any individual but with many causes & clinical associations

Decreased lung compliance

Increased gas diffusion distance


What is 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


What are 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”

idiopathic pulmonary fibrosis,
many pneumoconioses (dust diseases)
collagen vascular diseases-associated lung diseases


What is idiopathic pulmonary fibrosis?

aka cryptogenic fibrosing alveoli's

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

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


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


What are pneumoconiosis?

“The dust diseases”

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


How small must particles inhaled be to reach the alveoli?


What is 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


What is hypersensitivity pneumonitis?

aka extrinsic allergic alveoli's

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


What is cystic fibrosis?

An inherited multiorgan disorder of epithelial cells affecting fluid secretion in exocrine glands and the epithelial lining of the respiratory, gastrointestinal and reproductive organs

Mostly affects Caucasians

Incidence 0.4 per 1000 live births

Autosomal recessive inheritance


What causes cystic fibrosis?

Mutation in CFTR gene
(Cystic fibrosis transmembrane conductance regulator gene on chromosome 7q31.2 )
Vast phenotypic variation due to variations in mutations, organs specific effects of the gene
Gene encodes a transmembrane chloride channel protein


What are the signs of cystic fibrosis?

Clinical presentation: Infancy (usually)
Abnormally viscous mucous secretions
Recurrent lung infections
Failure to thrive
Recurrent intestinal obstruction
Pancreatic insufficiency


How does CF affect the lung?

Bronchioles distended with mucus
Hyperplasia mucus secreting glands
Multiple repeated infections
Severe chronic bronchitis and bronchiectasis


How does CF affect the pancreas?

Exocrine gland ducts plugged by mucus
Atrophy and fibrosis of gland
Impaired fat absorption, enzyme secretion, vitamin deficiencies (pancreatic insufficiency)


How does CF affect 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