Inhalation of Airborne Particles (haemolysis assay) Flashcards
What are the 3 main ways foreign substances can enter the human body
Ingestion, absorption, inhalation
How do particles usually elicit harmful effects
Through the generation of reactive oxygen species (ROS)
What particles can enter the upper respiratory tract
Coarse inhalable 2.5-10 um
What particles can enter the lower respiratory tract
Fine inhalable 0.1-2.5um
What particles can enter the distal respiratory tract
Nanoparticles
What respirable particles can cause haemolysis
DQ12 (silica particle), Cab-O-sil (silicon dioxide/ silica particle)
Do all respirable particles directly cause haemolysis
No, all respirable particles do not cause haemolysis. From the results of the haemolysis assay it was observed that both DQ12 and Cab-O-sil cause haemolysis however TiO2 particles did not cause any haemolysis
How do inhaled particles cause lung damage/ injury via the generation of ROS
Inhaled particles can cause injury/ damage via the generation of ROS both directly and indirectly
How do inhaled particles cause lung injury/ damage via the generation of ROS directly
Inhaled particles are capable of generating ROS which can interact directly with cell membranes causing lipid peroxidation. Lipid peroxidation can cause cell membranes to break causing cell lysis e.g. silanol groups (SiOH) can form hydrogen bonds with oxygen or nitrogen groups in biological membranes causing loss of membrane integrity and cell death
What happens if ROS accumulate inside cells within vesicles or the cytoplasm
Can cause oxidative damage to organelles and even DNA within the nucleus. Particles containing metal oxides can generate ROS via the Fenton and Harber-Weiss reactions
How do inhaled particles cause lung injury/ damage via the generation of ROS indirectly
The presence of particles and the damage caused to cells by particles can recruit inflammatory cells which can then release ROS into the lungs. Macrophage-mediated phagocytosis involves the release of ROS O2- (respiratory burst). This particular indirect damage is the main driver in asbestosis. Crystalline silica may also damage the lung indirectly by stimulating production of phagocytic-derived oxygen metabolites such as superoxide anion (O2-), hydroxyl radical (H2O2). All have been associated with membrane damage and cell lysis and can damage tight junctions between epithelial cells in culture
How do inhaled particles cause damage to the systemic circulation and indeed other organs
Inhaled particles (especially nanoparticles) can cross the airway epithelium into the circulatory or lymphatic system. It is clear that if ROS generating particles come into contact with RBCs they can cause them to lyse. The fact that particles can enter systemic circulation means that they can translocase and cause damage to other organs via similar mechanisms. Even if the particles do not cross into the systemic circulation the effects can still be observed e.g. inflammatory cells, ROS and inflammatory cytokines within the lungs are mirrored within the systemic circulation
Describe the causes of asbestosis
Diffuse parenchymal lung fibrosis as a result of heavy or prolonged exposure to asbestos, lag time 10-25 years
Describe the clinical features of asbestosis
Cough, progressive dyspnoea, bibasal crackles and frequently include clubbing, restrictive ventilator defects and impaired gas diffusion
Describe the chest x-ray of someone with asbestosis
Bilateral reticulonodular shadowing
Describe a CT of someone with asbestosis
Can show early fibroticchanges, asbestos bodies observed within areas of fibrosis (microscopy sections)
Describe the history of exposure of someone with silicosis
Quarrying/ grinding/ dressing of sandstone, granite or slate; developing tunnels (e..g coal miners); boiler scaling; sandblasting; pottery industry. Silicon e.g. DQ12 or Cab-O-sil
Describe the x-ray of someone with silicosis
Simple nodular fibrosis but no significant symptoms, signs or impairment observed
What does complicated silicosis result in
Progressive fibrosis, loss of lung function and breathlessness.
Describe the silicotic nodule
Consists of concentric layers of collagen surrounding a central area of dust
What do people with silicosis have
Increased risks of developing TB and lung cancer
What does a chest x-ray of complicated silicosis show
Nodular opacities particularly in the upper lobes. Egg shell calcification of hilar lymph nodes, pleural thickening may occur
How does someone get Coal Worker’s Pneumoconiosis
Development of this disease is directly related to total exposure to coal dust
Describe simple Coal Worker’s Pneumoconiosis
Small (
Describe complicated Coal Worker’s Pneumoconiosis
Characterised by large black fibrotic masses in the lung parenchyma, consisting of coal dust and collagen bundles. Typically located in the upper zones and appear as opacities on chest x-ray. Cavitation may occur and may result in expectoration of black sputum (melanoptysis). Often results in dyspnoea, restrictive ventilator defects and impaired gas diffusion
Describe causes of mesothelioma
Malignant tumour of the pleura at leat 90% of cases are from asbestos exposure. Exposure period may be short (few months), lag time to mesothelioma appearance is typically 20-40 years
How does mesothelioma usually present
With pain, dyspnoea, weight loss, lethargy and pleural effusion. Occasionally a lobulated pleural mass can be observed (X-ray). CT scans typically show nodular pleural thickening encasing the lung and involving the mediastinal pleura
