15, 16 - Pathology of Respiratory System Flashcards
Conducting airways have what type of epithelium
Pseudostratified ciliated columnar mucus secreting epithelium
Type I pneumocytes involved in…
Gas exchange
Type II pneumocytes involved in…
Surfactant
When is respiratory failure diagnosed?
PaO2
Causes of respiratory failure inc. defects in
Ventilation
Perfusion
Gas exchange
Type I respiratory failure
paCO2
Type II respiratory failure
paCO2 >6.3kPa
Hypercapnic respiratory drive
Wheeze vs stridor
Proximal vs distal airway obstruction
Crackles on auscultation indicate:
Resisted opening of small airways
Wheeze on auscultation indicate:
Narrowed small airways
Bronchial breathing on auscultation indicate:
Sound conduction through solid lung
Pleural rub on auscultation indicates:
Relative movement of inflamed visceral and parietal pleura
Dull percussion indicates:
lung consolidation or pleural effusion
Hyper resonance indicates:
Pneumothorax or emphysema
VITAMIN D
Vascular Inflammation Trauma Autoimmune Metabolic Infectious Neoplastic Degenerative
What is a benign primary lung tumour called
Adenochondroma
Rough survival rate of lung tumours
5%
Risk factors of lung carcinoma
Cigarettes
Asbestos
Lung fibrosis - inc. asbestosis, silicosis
Radon
Chromates, nickel, tar, hematite, arsenic, mustard gas
Types of asbestos
Amphiboles - blue + brown
Serpentines - white
Most dangerous asbestos
Blue (crocidolite)
Pneumoconiosis is?
Dust related pneumonia
What jobs are related to asbestos?
Insulation work
Ship building & repair
Asbestos textile work
Manufacture of gas masks
Types of malignant primary lung tumours
Non-small cell carcinoma (85%) of which 52% are squamous
Small cell carcinoma (neuroendocrine) (15%)
Secondary tumours are more common but the presenting feature is different…
Multiple nodules generally
Primary vs secondary tumours how to distinguish
History
Morphology
Antigen expression
Lung non-mucinous adenocarcinoma and small cell immunocytochemistry
Cytokeratin & thyroid transcription factor positive
Colorectal immunocytochemistry
Cytokeratin 7 negative & cytokeratin 20 positive
Upper GI tract immunocytochemistry
Cytokeratin 7 positive & cytokeratin positive
Breast immunocytochemistry
May be oestrogen receptor positive
Melanoma immunocytochemistry
S100, HMB45, MelanA positive, cytokeratin negative
Common lung carcinoma sites
Most central, main or upper lobe bronchus
Adenocarcinoma is more peripheral
Squamous carcinoma features
+/- keratinisation
Roughly 90% in smokers
Central > peripheral
Hypercalcaemia due to parathyroid related peptide
What is the epithelium of bronchi?
Pseudostratified columnar epithelium with ciliated and mucus-secreting cells
What is squamous metaplasia?
- irritants cause epithelium to reversibly change from pseudostratified columnar to stratified squamous which can keratinise
What is dysplasia?
One metaplastic cell undergoes irreversible changes producing the first neoplastic cell
Adenocarcinoma features
Glandular cells, serous +/- mucus vacuoles
Central equivalent to peripheral
80% in smokers
Thyroid transcription factor is expressed in many non-mucinous lung adenocarinomas
Bronchioloalveolar carcinoma features
Spread of well differentiated mucinous or non-mucinous neoplastic cells on alveolar walls
Not invasive i.e. adenocarcinoma in situ
Mimics pneumonia
Uncommon nodal & distant mets
Neuroendocrine cell proteins
Neural cell adhesion molecule (CD56)
Neurosecretory granule proteins - chromogranin, synaptophysin
Neuroendocrine cell in normal mucosa is called…
Kulchitsky cells
Typical carcinoid tumour features
Grow into and occlude a bronchus
Organoid, bland cells, no necrosis,
Atypical carcinoid tumour features
11% of lung carcinoids Less organoid, more atypia, nucleoli Necrosis, 2-10 mitotic figure per 2sqmm 70% meta 60% 5yr survival
Large cell neuroendocrine carcinomas morphology
Organoid architecture, eosinophilic granular cytoplasm
Antigen expression
Large cell neuroendocrine features
Severe atypia, nucleoli, necrosis, >11 mitotic figures per 2spmm
Prognosis similar/worse than non-small cell lung carcinomas
Associated with smoking
Small cell carcinoma features
Rapidly progressive malignant tumours
Neurosecretory granules with peptide hormones such as ACTH
Could have small primary w/ met at presentation
99% are smokers
Large cell carcinoma features
No specific squamous/glandular morphology
50% express thyroid transcription factor
Can be neuroendocrine
Staging on lung malignancy uses what system?
TNM
TNM T1
Diam:
T1a:
TNM T2
Diam: T2a: 3-5cm T2a: 5-7cm Scopy: >2cm to carina Atelectasis: lobar atelectasis or obstructive pneumonia to hilus
TNM T3
Diam: >7cm
Scopy:
TNM T4
Scopy: tumour in carina
Invasion: heart great vessels, trachea, eoso, spine
Nodules: nodules in other ipsilateral lobes
Epidermal growth factor receptor tyrosine kinase inhibitors
Oral
Less toxic vs standard cytotoxic chemo
Inhibits mitotic cycle
Not curative but stabilises progression until resistance mutations develop
ALK gene short for?
Anaplastic lymphoma kinase gene
ALK gene features
Detect mRNA by FISH, CISH of RT-PCR
Present in 10% of lung adenocarcinomas
Non-smoking, Asian, women
Crizotinib
ATP analog inhibits ALK, ROS1, c-MET tyrosine kinases
Temporary control
Effective in 90% of tumours
$100,000 per patient per year
Causes of pleural effusion
Inflammatory: serous/fibrinous - exudate
Non-inflammatory: congestive heart failure
LDH, pH, glucose of fluid can be measured for diagnosis
Cytology used to assess presence of malignant or inflammatory cells
Pleural tumour types
Benign - rare
Malignant - common
Usually secondary adenocarcinoma
Primary malignant mesothelioma is rarer
Malignant mesothelioma
> 90% associated with asbestos exposure, blue or brown most hazardous
Exposure may be low level
Long latent period of 15 to 60 years
Malignant mesothelioma establishment steps
- Initial nodule and effusion
- Obliterates pleural cavity growing around the lung
- Invades chest wall (pain) and lung
- Nodal and distant and metastases less common than with carcinomas
- Mixed spindle cell and epithelioid cells. May be very fibrous (desmoplastic)
How to differentiate adenocarcinoma from malignant mesothelioma
Cellular antigen expression (immunocytochemistry on cytology or biopsy)
Symptomatic treatment
Uniformly fatal in usually
Virchow’s triad reminder
Endothelial injury
Stasis of blood flow
Hypercoagubulity
Secondary infection due to problems with:
Mucocilliary escalator: physical obstruction, cough reflex, ciliary dysmotility (kartagener’s syndrome), mucus viscosity
Immunity: hypogammaglobulinaemia, lymphomas, immunosuppressive drugs, AIDS; macrophage function: smoking, hypoxia
Pulmonary oedema
Common infections of respiratory system
Acute brochitis Bronchiolitis Pneumonia Bronchopneumonia Lobar pneumonia Atypical pneumonias Non-infected pneumonias Pulmonary TB
Acute bronchitis which virus causes it
Respiratory Syncytial Virus (RSV)
H.influenzae
Strep. pneumoniae
Bronchiolitis what is it?
Primary acute infection that occurs in infants.
Caused by RSV
Rare
What is pneumonia?
Inflammatory exudate in alveoli & distal small airways - consolidation
Classifications of pneumonia
Clinical - primary of secondary
Aetiological - bacterial, viral, fungal
Anatomical - lobar pneumonia or bronchopneumonia
Reaction - purulent, fibrinous
Bronchopneumonia features
Secondary - compromised defences Low virulence bacteria or occasionally fungi Common Patchy Bronchocentric Resolve or heal w/ scarring
Lobar pneumonia features
Primary - mainly male 20-50 yo 90% virulent Strep pneumoniae Uncommon Confluent segments - whole lobe or lobes with overlying pleuritis Red to grey hepatisation Klebsiella pneumonia
What is red to grey hepatisation?
A state where the lungs is engorged with matter, so no longer pervious to air.
Red is when there are RBCs, neutro, fibrin in pulm. alveolus.
Precedes, grey. Where RBCs have been broken down to fibrinosuppurative exudate.
What is Klebsiella pneumoniae?
Anaerobic, gram–ve, rod-shaped bacteria that causes pneumonia.
Mainly found in soil.
Affects elderly, diabetic and alcoholic people the most.
Atypical pneumonias in non-immunosuppressed - causative agents
Viral - flu, varicella, RSV, rhino, measles
Mycoplasma pneumonias - chronic fibrosis
Chlamydia, Coxiella burnetti (Q-fever)
Legionella pneumophilla - systemic, 10-20% fatal
Atypical pneumonias in non-immunosuppressed - features
Severity mild to fatal
Interstitial lymphocytes, plasma cells, macrophages
Intra-alveolar fibrinous cell-poor exudate
Diffuse alveolar damage
Atypical pneumonias in immunosuppressed - causative agents
Fungi - candida, aspergillus, pneumocystis carinii
Viruses - CMV (cytomegaly virus), (herpes simplex) HSV, measles
Non-infected pneumonias
Aspiration - 2* infection often with mixed anaerobes producing abscesses
Lipid - endogenous (retention pneumonitis), exogenous (aspiration)
Cryptogenic organising pneumonia (COP)
Bronchiolitis obliterans organising pneumonia (BOOP)
Pulmonary TB - causative agent
Mycobacterium TBosis
Pulm TB vaccine name
Bacille Calmette-Guerin (BCG)
Pulm TB - features
Asymptomatic, Ghon complex in peripheral lung & hilar nodes which usually resolves
Atypically reactivates
Pulm TB - disease progression
Empyema
Pneumonia
Miliary or more limited spread to other organs - bone, kidney
Scarring - fibrous calcified scar
Pulm TB - what we see
Granulomas with multinucleated Langhan’s giants cells & caseous necrosis
Few bacilli but intense immune rxn causing tissue damage
Type IV hypersensitivity to tuberculin - Heaf & Mantoux tests
Pulmonary vascular diseases
Pulm. vasculitis
Emboli
Obstructive
Bronchiectasis
Pulm vascular diseases - what are they?
Vessel wall inflammation (vasculitis)
Obstruction of flow
Haemodynamic disturbances
Pulmonary vasculitis
Necrotising granulomatous vasculitis - Wegener’s granulomatosis; Churg-strauss syndrome
Goodpasture’s syndrome - anti-glomerular basement membrane antibody, intra-alveolar haemorrhage & glomerulonephritis
Microvascular damage - ARDS & DAD, SLE
Obstruction via emboli - type of emboli
Thromboemboli - common, DVTs, size determines symptoms Fat emboli Air Amniotic fluid Tumour Foreign bodies
What is bronchiectasis?
Permanent dilation of bronchi and bronchioles caused by destruction of the muscle and elastic tissue
Results from chronic necrotising infection
Rare
Predisposing conditions for bronchiectasis
CF Primary ciliary dyskinesia Kartagener syndrome Bronchial obstruction Lupus, rheumatoid, IBD, GVHD (graft-versus-host-disease)
Types of COPD
Chronic bronchitis and emphysema
What is chronic bronchitis?
Cough and sputum for 3 months in each of 2 consecutive years
At bronchi
Caused by chronic irritation
Middle aged and old
Pathology of chronic bronchitis
Mucus gland hyperplasia and hypersecretion
Secondary infection by low virulence bacteria
Chronic inflammation
What is emphysema?
Abnormal permanent dilation of airspaces distal to the terminal bronchiole with destruction of airspace wall, w/o fibrosis
Why does emphysema occur?
Overinflation
Classification of emphysema
Centrilobular
Panlobular
Paraseptal
Centrilobular emphysema
Centiacinar
Coal dust, smoking
Panlobular emphysema
Panacinar
>80% a1 antitrypsin deficient
Rare, AD
Severe in lower lobe bases
Paraseptal emphysema
Distal acinar
Upper lobe subpleural bullae adjacent to fibrosis
Will cause PT if ruptured
Stereotype for predominant bronchitis
Blue bloated
Stereotype for predominant emphysema
Pink puffer
What is asthma?
Chronic inflammatory disorder of the airways
Paroxysmal bronchospasm
What problems does asthma cause?
Mucosal inflammation & oedema
Hypertrophic mucous glands & mucous plugs in bronchi
Hyperinflated lungs
Clinicopathological classification
Atopic
Non-atopic
Aspirin-induced
Allergic bronchpulmonary aspergillosis (ABPA)
Atopic asthma - pathology
Allergen - dust, pollen, animal products
Cold, exercise, resp infection
Degranulation of IgE bearing mast cells
Interstitial lung disease features
Diffuse and chronic
Disease of pulm connective tissue
Restrictive disease
Unknown cause
What interstitial lung disease does to lungs
Increased tissue in alveolar-capillary wall
Decreased lung compliance
Increased gas diffusion distance
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 resp distress syndrome
Chronic interstitial lungs disease presentation
Dyspnoea increasing for months to years
Clubbing, fine crackles, dry cough
Interstitial fibrosis & chronic inflammation
‘Honeycomb lung’
Chronic interstitial lung disease e.g.s
Idiopathic pulm fibrosis
Pneumoconioses
Sarcoidosis
Collagen vascular disease-associated lung disease
Idiopathic pulm. fibrosis features
Aka cryptogenic fibrosing alveolitis
5000 new cases pa
3&5 year mortality (43%, 57%)
Sub-pleural, lower lobes affected first & most severely.
Idiopathic pulm. fibrosis histology
Usual Interstitial pneumonia
Interstitial chronic inflammation & variably mature fibrous tissue
Adjacent normal alveolar walls
Similar pattern of fibrosis in collagen vascular disease - cobblestone
Sarcoidosis features
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
What are pneumoconiosis?
Dust diseases
Non-neoplastic lung diseases due to inhalation of dusts, fume, vapours
What size diameter does dust need to be to reach alveoli?
Coal workers’ pneumoconiosis
Anthracosis
Simple macular or could be nodular
Progressive massive fibrosis
COPD if >20 yrs underground mining
Silicosis
Silica - sand and stone dust Kills phagocytosing macrophages Fibrosis & fibrous silicotic nodules Possible reactivation of TB Increased risk of lung carcinoma
Asbestosis
High level exposure produces interstitial fibrosis
Histologically like idiopathic pulm. fibrosis but asbestos bodies are identifiable in tissue sections
Hypersensitivity pneumonitis
Aka extrinsic allergic alveolitis
Type III hypersensitivity reaction to organic dusts
E.g. farmers’ lung (actinomycetes in hay); pigeon fanciers’ lung (pigeon antigens)
Peribronchiolar inflammation w/ poorly formed non-caseating granulomas extends alveolar walls.
Repeated episodes lead to interstitial fibrosis
CF
Inherited multiorgan disorder of epithelial cells affecting fluid secretion in exocrine glands and the epithelial lining of the resp, GI and repro organs.
Mainly Caucasians
0.4 per 1000 live births
AR
CTFR gene - transmembrane chloride channel protein
CF - clinical presentation
Infancy Abnormally viscous mucous secretions Recurrent lung infections Failure to thrive Recurrent intestinal obstruction Pancreatic insufficiency
CF - affects on lung
Bronchioles distended with mucus
Hyperplasia mucus secreting glands
Multiple repeated infections
Severe chronic bronchitis and bronchiectasis
CF - affects on pancreas
Exocrine gland ducts plugged by mucus
Atrophy and fibrosis of gland
Impaired fat absorption, enzyme secretion, vitamin deficiencies
CF - other organs
Small bowel - mucus plugging (meconium ileus)
Liver - plugging of bile cannaliculi - cirrhosis
Salivary glands - similar to pancreas: atrophy & fibrosis
95% of males are infertile
