Restrictive lung diseases: ARDs, fibrosis, asbestosis, sarcoidosis Flashcards
Define ARDS
non-cardiogenic pulmonary oedema and diffuse lung inflammation syndrome
3 criteria:
- acute onset (1 week)
- Bilateral opacities on xray
- PaO2/FiO2 ratio <300 on PEEP or CPAP
Commonly 2/2 critical illness but can be caused by direct lung trauma
Explain the pathogenesis of ARDS
-
Diffuse alveolar damage → injury to the alveolar-capillary membrane
- made up of type I and type II alveolar pneumocytes and capillary endothelial cells
- The alveolar air spaces are subsequently flooded with fluid, inflammatory cells and inflammatory mediators
- Early exudative inflammatory phase progresses to a fibroproliferative phase
- Fibrous tissue and collagen deposition → irreversible and sometimes catastrophic lung fibrosis
State some direct and indirect causes of ARDS
Sepsis with pulmonary origin is the most common cause (pneumonia)
DIRECT/PULMONARY
- aspiration- of gastric contents . 1/3rd hospitalised PTs with aspiration develop ARDS
- burns and smoke inhalation (inc. e-cigarettes)
- pulmonary contusion
- transfusion-related lung injury
- drowning
- cardiopulmonary bypass
- fat embolism
- lung transplantation- primary graft dysfunction
INDIRECT/SYSTEMIC
- sepsis
- severe acute pancreatitis
- severe trauma- haemorrhagic shock or later onset of multiple organ failure
- Multiple blood transfusions
- DIC
- Obstetric events: eclampsia, amniotic fluid embolus
-
Drugs/toxins: aspirin, heroin, paraquat, alcohol misuse
- depletion of endogenous antioxidants
Summarise the epidemiology of ARDS
1 in 6000 annually in UK
Identify appropriate investigations for ARDS and interpret the results
CXR
findings are similar to cardiogenic pulmonary oedema (heart failure). These are classically:
- A - alveolar oedema (bat wing opacities)
- B - Kerley B lines.
- C - cardiomegaly.
- D - dilated upper lobe vessels.
- E - pleural effusion.
ABG
- PaO₂/FiO₂ (inspired oxygen) ≤300 on maximum oxygen Tx
Test for underlying infection:
- urine culture
- sputum culture
- blood culture
- amylase/lipase in acute pancreatitis
- ESR/CRP
Check for normal cardiac function
- BNP- normal in ARDS. Sign of cardiac failure if high
- echocardiogram- abnormal suggests cardiogenic pulmonary oedema rather than ARDS.
State and define the 2 lung diseases caused by exposure to asbestos
Asbestosis
Diffuse interstitial fibrosis of the lung as a consequence of exposure to absestos fibres
Malignant mesothelioma
Aggresive mesothelial neoplasm arising from the pleura (90%)/peritoneum/pericardium/tunica vaginalis
- Direct causative link with asbestos exposure
What are the presenting symptoms of ARDS?
Acute onset:
- Dyspnoea
- Tachypnoea (RR>20)
- Fever
- Cough- may have frothy/pink sputum in pulmonary oedema
- Pleuritic chest pain
What are the presenting signs of ARDS O/E?
- Hypoxemia (SaO2 low despite supplementary oxygen)
- Tachycardia
- Cyanosis
- Bilateral diffuse fine inspiratory crepitations
- Peripheral vasodilation
Identify appropriate investigations for asbestosis
CXR: interstitial fibrosis in the lower zones and bilateral pleural thickening
Pulmonary function test: shows restrictive changes
- reduced FVC
- reduced TLC
HRCT chest
Bronchial lavage- presence of asbestos bodies
Lung biopsy- rarely needed
Explain the pathogenesis of asbestosis and asbestos-related pleural changes
When asbestos fibres are inhaled, they deposit at alveolar duct bifurcations and cause an alveolar macrophage alveolitis.
Recruitement and activation of macrophages release cytokines (eg TNFa and IL-1b) and oxidant species:
- → fibrosis (starts in lower lobes)
-
→ oxidative stress, DNA damage, alterations in gene expression (proto-onco + tumour supressor)
- → malignant changes
Summarise the epidemiology of asbestos-related lung disease
More common in men and older adults
There is a latency period of around 20 years from time of first exposure to asbestos to development of radiographical changes in asbestosis
Asbestos exposure is documented in 80% of cases of mesothelioma
(shipyard, construction, maintenance)
What are the presenting symptoms/signs of asbestosis
Progressive dyspnoea
Dry, non-productive cough (unlike COPD which is productive)
Clubbing in advance disease due to hypoxia
Recognise the signs of mesothelioma O/E
- Dyspnoea
- Quiet breath sounds- due to pleural effusion, bronchial obstruction
- Dullness to percussion (due to pleural effusion)
- Abdo extension in peritoneal mesothelioma
-
Constitutional symptoms:
- fatigue
- fever
- sweats
- weight loss
Identify appropriate investigations for mesothelioma
- CXR- pleural thickening/effusion. May show pleural mass and rib destruction
- CT contrast chest- pleural thickening and/or discrete pleural plaques, pleural and/or pericardial effusions; enlarged hilar and/or mediastinal lymph nodes; chest wall invasion
- Pleural fluid: may be blood stained
- Video-assisted thoracoscopic surgery (VATS)- diagnostic, obtain pleural biopsy for histological analysis
- Immunohistochemistry- specific markers eg keratins 5/6
- Pulmonary function tests- suitability for surgery
Define idiopathic pulmonary fibrosis
Rare, chronic, inflammatory lung disease that manifests over several years and is characterised by the formation of scar tissue within the lungs and progressive dyspnoea.
Explain the pathogenesis of idiopathic pulmonary fibrosis
Explain the pathogenesis of idiopathic pulmonary fibrosis
Define idiopathic pulmonary fibrosis
Rare, chronic, inflammatory lung disease that manifests over several years and is characterised by the formation of scar tissue within the lungs and progressive dyspnoea.
Explain the pathophysiology of iodipathic pulmonary fibrosis
Occurs in genetically predisposed individuals
- Environmental insult triggers pro-inflammatory, pro-fibrotic response
- Pneumocytes secrete cytokines and growth factors -TGFb1
- → influx of macrophages, fibroblasts and other pro-inflammatory cells
- Normal tissue repair process is dysregulated, and fibroblast activity persists
- Leads to progressive fibrosis as collagen continues to be synthesised and deposited in the interstitial layer
- Gas exchange is reduced and alveoli become less compliant/stiffer
- Loss of alveoli → thick-walled cysts = honeycombing.
What are the presenting clinical signs of idiopathic pulmonary fibrosis?
-
Dry (‘velcro’), basalar end-inspiratory crackles
- WITHOUT signs of congestive HF
- Clubbing- late/rare
- signs of RHF in severe disease
What investigations would you do for idiopathic pulmonary fibrosis?
Bloods
- Inflammatory markers- CRP, ESR
- Serology- ANA in 20%, RF in 20%, anti cyclic cirrulinated peptide normal
- (exclude collagen vascular abnormalities)
- SaO2 reduced on exercise, pCO2 rises in late disease
Imaging
- CXR- bilateral basal opacities. Initially gound glass, then honeycombing in late disease
- HRCT- diagnostic
Further tests
-
Pulmonary function tests
- reduced FVC + FEV1
- reduce TLC
- restrictive features
-
Biopsy
- thoracoscopy- if HRCT/clinical evaluation not diagnostic
- patchy interstitial inflammation
- fibroblastic foci- patchy fibrosis of varying ages
-
Brochoalveolar lavage
- if diagnostic uncertainty
- raised in chronic hypersensitivity pneumonitis
Define + categorise lung cancer
A group of malignant epithelial tumours arising from cells lining the lower respiratory tract.
Lung cancer is divided into two categories:
- Non-small cell lung cancer (NSCLC) and Small cell lung cancer (SCLC)
- NSCLC accounts for more than 80% of all lung cancers- three main types:
- adenocarcinoma
- squamous cell carcinoma
- large cell carcinoma
What are the presenting symptoms of lung cancer?
KEY SYMPTOMS
-
Cough
- new/persistent cough in a smoker = HIGH SUSPICION
-
Dyspnoea
- due to: pleural effusion, airway obstruction, underlying COPD, post-obstructive pneumonia
- Haemoptysis
-
Chest pain
- lung itself has no pain fibres- due to invasion of tumour into pleura/chest wall
-
Pancoast tumours:
- Horner’s syndrome- due to sympathetic plexus dysfunction
- shoulder pain- due to invasion of brachial plexus
- weakness/atrophy/parasthesia of C8-T1
- Weight loss/malaise/fatigue
Due to seondary effects of cancer:
-
Hoarseness
- recurrent larygeal nerve paralysis
-
Confusion/personality changes/headache/seizures/N+V
- 25% lung cancer patients develop brain mets
-
Bone pain/fracture
- mets commonly affect axial skeleton and long bones
-
Dysphagia
- compression of tumour/enlarged mediastinal lymph nodes on oesophagus
What are the signs of lung cancer on physical examination
May be no signs
- Fixed monophonic wheeze - suggesting fixed focal obstruction
-
Signs of lobar collapse / pleural effusion
- tracheal deviation
- crackles
- absent breath sounds
- signs of mets:
- cervical/supraclavicular lymphadenopathy
- bone tenderness
- proximal myopathy
- distal neuropathy
- Clubbing- NSCLC
What imaging investigations would be appropriate for suspected lung cancer?
CXR
may detect:
- single or multiple pulmonary nodule(s)
- mass
- pleural effusion
- pneumothorax/lobar collapse
- mediastinal or hilar fullness
Contrast-enhanced CT of the lower neck, chest, and upper abdomen -
- shows size, location and extent of primary tumour
- evaluates for hilar and/or mediastinal lymphadenopathy
- shows distant metastases
- staging
For metastases:
- MRI/CT brain
- PET-CT
- Bone scan
What non-imaging investigations would you do for lung cancer?
Diagnostic:
- Bronchoscopy with brushings or biopsy – if lesion is accessable
- CT/US-guided percutaneous biopsy- for suspicious peripheral pulmonary lesions not accessible with bronchoscopy.
- Sputum and pleural fluid cytology
- Lymph node biopsy
Bloods
- FBC- normal/anaemia
- U&Es- may have hyponatraemia
- Calcium (hypercalcaemia is a common feature)
- ALP (raised with bone metastases)
- LFTs- raised in liver mets
What is the name for an apical lung cancer? Explain the specific signs and their pathophysiology
Pancoast tumours
These tumours are located in the superior sulcus of the lung
Invade through the structures of the thoracic inlet:
-
Parietal pleura
- Shoulder pain
- Lower branches of the brachial plexus
- parasthesia, wasting of intrinsic muscles of hand (ulner nerve damage)
-
Ribs 1+2/periosteum and cervical spine bodies
- severe pain
-
Subclavian vein/artery → SVC syndrome
- decreased venous return from upper extremities, face + thorax to RA
- leads to oedema, cyanosis, vessel distension
- Upper sympathetic ganglion
- Horners Syndrome
-
Recurrent laryngeal nerve
- Hoarseness
Compare SCLC/NSCLC:
- Location
- Growth rate
- Associations
- Prognosis
SMALL CELL (20%)
- central tumours
- Fast-growing, metastasise
- associated with SIADH (ectopic scretion of ADH by tumour)- causing hyponatraemia
- very poor prognosis- 5yr survival = 1-24%
NON-SMALL CELL (80%)
- peripheral tumours
- Slower growing
- SCC associated with PTH release → hypercalcaemia
- adenocarcinoma associated with non-smokers
- Prognosis slightly better but depends on stage
- can be resected
- large cell = poor
List some differentials for a lung nodule on CXR
- Malignancy – primary or secondary
- Abscess
- Granuloma
- Carcinoid tumour
- Pulmonary hamartoma (rare, benign)
- AV malformation
- Cyst
- Foreign body
- Skin tumour
Explain the pathophysiology of pneumoconiosis
Smaller silica/coal/dust particles of =<5 microns gain access to the alveoli, are ingested by macrophages, and cause cytolysis of the macrophage.
Macrophages generate fibrogenic proteins and GF → stimulate collagen elaboration → fibrosis
What investigations would you do for pneumoconiosis?
- Simple: micronodular mottling
- Complicated:
- Nodular opacities in upper lobes
- Micronodular shadowing
- Eggshell calcification of hilar lymph nodes (characteristic of silicosis)
- Bilateral lower zone reticulonodular shadowing and pleural plaques (in asbestosis)
- CT Scan - fibrotic changes can be visualised early
- Bronchoscopy - allows visualisation and bronchoalveolar lavage
- Lung Function Tests - restrictive pattern
