Lecture 15 Lung Toxicology

Question 1

What parts of respiratory system is exposed to external environment?

Answer 1

All of respiratory system, from nostrils to alveoli

Question 2

Do toxicants in the blood reach the respiratory system early or late?

Answer 2

Early, first location blood reaches from right ventricle

Question 3

What are the two categories of effects of inhaled toxicants?

Answer 3

Local: nasal, upper and lower airways
Distant: into blood, distant organs

Question 4

What is the function of the nasal passage?

Answer 4

Humidifies and warms air.
Filters large particles
Captures water soluble gases
Has CYP P450s

Question 5

What are the two types of alveoli cells and their respective functions?

Answer 5

Type 1 pneumocytes: line alveolar spaces, creates a thin barrier for gas exchange
Type 2 pneumocytes: located in corner of alveoli, produce surfactant. Reduce surface tension so alveoli remain open.

Question 6

What is the direction of flow of mucus in the nose?

Answer 6

Goes downwards toward larynx, to swallow

Question 7

What is the direction of flow of mucus in the lower airway?

Answer 7

Upward towards larynx, to swallow or expectorated

Question 8

Why are different environments found in each region of respiratory airways? (hint: particle size)

Answer 8

Upper airways trap large particles, smaller particles reach lower airways

Question 9

How does water solubility of inhaled gases affect region of toxicity?

Answer 9

Highly soluble gases e.g. SO2, get trapped by nasal fluid in early respiratory airway. Relatively water insoluble e.g. ozone, penetrate deep into lung. Very water insoluble e.g. CO, reach alveoli

Question 10

Mechanisms of deposition: what is impaction?

Answer 10

Particles are deposited because blocked by a bifurcation point

Question 11

Mechanisms of deposition: what is interception?

Answer 11

Particle trajectory brings it into contact with airway epithelium (large airways)

Question 12

Mechanisms of deposition: what is sedimentation?

Answer 12

Due to gravity, flow diminishes, leading to sedimentation (small airways)

Question 13

Mechanisms of deposition: what is diffusion?

Answer 13

No more flow, just random Brownian motion and eventually deposit (alveoli)

Question 14

What are some natural mechanisms to protect in acute lung injury?

Answer 14

Breath holding –> trigeminal nerve

Bronchoconstriction –> vagus nerve

Question 15

What are the potential effects of acid/alkali toxicants?

Answer 15

Cell necrosis –> increase permeability of alveolar wall –> pulmonary oedema decreases gas exchange

Question 16

What are the beneficial and harmful effects of ROS produced by the host?

Answer 16

ROS is part of host defence and aims to kill invading microbes. However if excessive will damage lung.

Question 17

What are the two chronic lung toxicity responses? Briefly outline their characteristics.

Answer 17

Emphysema: absence of fibrosis, destruction of gas exchange surface so creates big empty lungs.
Fibrosis: increased collagen deposition, lungs go stiff

Question 18

Name causes of emphysema

Answer 18

Smoking (mainly), cadmium oxide

Question 19

Does emphysema exhibit increased or decreased compliance?

Answer 19

Increased compliance (ability of lung to stretch and expand) due to reduced exchange surface.

Question 20

What is the effect of reduced flow/movement in emphysema?

Answer 20

Air trapping

Question 21

What causes emphysema?

Answer 21

Smoking reduces activity of alpha1 anti-protease. Causes diffuse destruction of alveolar and bronchiolar walls.

Question 22

In fibrosis, which type of collagen increases?

Answer 22

Type 1 collagen, is more stiff

Question 23

Does emphysema cause decrease/increase of vital capacity, and decrease/increase of reserve volume?

Answer 23

Increases vital capacity (more space in lungs due to destruction of walls), increases reserve volume (lungs not collapsing properly, cause air trapping)

Question 24

Does fibrosis cause decrease/increase of vital capacity, and decrease/increase of reserve volume?

Answer 24

Decreases vital capacity (more collagen takes up space), decreases reserve volume.

Question 25

Name most common asbestos substances.

Answer 25

Chrysolite (white, common in buildings)

Amosite (brown, needle fibres)

Question 26

Is asbestos bodies or asbestos fibres more related to pulmonary toxicity?

Answer 26

Asbestos bodies more dangerous.