Inhalation of Airborne Particles (haemolysis assay)

Question 1

What are the 3 main ways foreign substances can enter the human body

Answer 1

Ingestion, absorption, inhalation

Question 2

How do particles usually elicit harmful effects

Answer 2

Through the generation of reactive oxygen species (ROS)

Question 3

What particles can enter the upper respiratory tract

Answer 3

Coarse inhalable 2.5-10 um

Question 4

What particles can enter the lower respiratory tract

Answer 4

Fine inhalable 0.1-2.5um

Question 5

What particles can enter the distal respiratory tract

Answer 5

Nanoparticles

Question 6

What respirable particles can cause haemolysis

Answer 6

DQ12 (silica particle), Cab-O-sil (silicon dioxide/ silica particle)

Question 7

Do all respirable particles directly cause haemolysis

Answer 7

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

Question 8

How do inhaled particles cause lung damage/ injury via the generation of ROS

Answer 8

Inhaled particles can cause injury/ damage via the generation of ROS both directly and indirectly

Question 9

How do inhaled particles cause lung injury/ damage via the generation of ROS directly

Answer 9

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

Question 10

What happens if ROS accumulate inside cells within vesicles or the cytoplasm

Answer 10

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

Question 11

How do inhaled particles cause lung injury/ damage via the generation of ROS indirectly

Answer 11

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

Question 12

How do inhaled particles cause damage to the systemic circulation and indeed other organs

Answer 12

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

Question 13

Describe the causes of asbestosis

Answer 13

Diffuse parenchymal lung fibrosis as a result of heavy or prolonged exposure to asbestos, lag time 10-25 years

Question 14

Describe the clinical features of asbestosis

Answer 14

Cough, progressive dyspnoea, bibasal crackles and frequently include clubbing, restrictive ventilator defects and impaired gas diffusion

Question 15

Describe the chest x-ray of someone with asbestosis

Answer 15

Bilateral reticulonodular shadowing

Question 16

Describe a CT of someone with asbestosis

Answer 16

Can show early fibroticchanges, asbestos bodies observed within areas of fibrosis (microscopy sections)

Question 17

Describe the history of exposure of someone with silicosis

Answer 17

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

Question 18

Describe the x-ray of someone with silicosis

Answer 18

Simple nodular fibrosis but no significant symptoms, signs or impairment observed

Question 19

What does complicated silicosis result in

Answer 19

Progressive fibrosis, loss of lung function and breathlessness.

Question 20

Describe the silicotic nodule

Answer 20

Consists of concentric layers of collagen surrounding a central area of dust

Question 21

What do people with silicosis have

Answer 21

Increased risks of developing TB and lung cancer

Question 22

What does a chest x-ray of complicated silicosis show

Answer 22

Nodular opacities particularly in the upper lobes. Egg shell calcification of hilar lymph nodes, pleural thickening may occur

Question 23

How does someone get Coal Worker’s Pneumoconiosis

Answer 23

Development of this disease is directly related to total exposure to coal dust

Question 24

Describe simple Coal Worker’s Pneumoconiosis

Answer 24

Small (

Question 25

Describe complicated Coal Worker’s Pneumoconiosis

Answer 25

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

Question 26

Describe causes of mesothelioma

Answer 26

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

Question 27

How does mesothelioma usually present

Answer 27

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