Respiratory Pathology Flashcards
What proportion of children are diagnosed with asthma?
1 in 10 UK children
What percentage of the UK population have COPD?
5%
What type of epithelium lines the conducting airways?
Pseudostratified cilliated columnar mucus secreting epithelium
How do you define respiratory failure?
PaO2
What is type I respiratory failure?
(paCO2
What is type II respiratory failure?
(paCO2>6.3kPa)
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?
adenochondroma
rare
What type of tumour makes up 90% of lung tumours?
carcinoma
What percentage of lung cancer is due to smoking?
80%
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
radon 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
asbestosis
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?
History Morphology 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?
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)
What is classed as T1 stage lung malignancy?
T1a=
What is classed as T2 stage lung malignancy?
T2a=3-5cm
T2b=5-7cm
> 2cm to carina
lobar atelectasis or obstructive pneumonia to hilus
What is classed as T3 stage lung malignancy?
> 7cm
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?
Inflammatory:
- 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?
Inflammatory:
- 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
asbestos
- effusion, fibrous plaques, diffuse fibrosis
Pleural tumours?
Benign - rare fibroma 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
Croup
Exacerbations of COAD
What are the features of pneumonia?
Inflammatory exudate in alveoli & distal small airways - consolidation
Classifications
Clinical - primary or secondary
Aetiological - Bacterial, viral, fungal
Anatomical - lobar pneumonia or bronchopneumonia
Reaction - purulent, fibrinous
What are the classifications of pneumonia?
Classifications: Clinical - primary or secondary Aetiological - Bacterial, viral, fungal Anatomical - lobar pneumonia or bronchopneumonia Reaction - purulent, fibrinous
Inflammatory exudate in alveoli & distal small airways - consolidation
Bronchopneumonia?
Secondary - compromised defences Often low virulence bacteria or occasionally fungi Common Patchy Bronchocentric Resolve or heal with scarring
What are the 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
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?
Uncommon
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?
Thromboembolic
- 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 Air Amniotic fluid Tumour Foreign bodies
What are obstructive pulmonary diseases?
Localised or diffuse obstruction of air flow
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)
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.
Asthma
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
Wheeze
Cough
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”
Examples: idiopathic pulmonary fibrosis, many pneumoconioses (dust diseases) sarcoidosis, 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
