Lecture 15 Lung Toxicology Flashcards
What parts of respiratory system is exposed to external environment?
All of respiratory system, from nostrils to alveoli
Do toxicants in the blood reach the respiratory system early or late?
Early, first location blood reaches from right ventricle
What are the two categories of effects of inhaled toxicants?
Local: nasal, upper and lower airways
Distant: into blood, distant organs
What is the function of the nasal passage?
Humidifies and warms air.
Filters large particles
Captures water soluble gases
Has CYP P450s
What are the two types of alveoli cells and their respective functions?
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.
What is the direction of flow of mucus in the nose?
Goes downwards toward larynx, to swallow
What is the direction of flow of mucus in the lower airway?
Upward towards larynx, to swallow or expectorated
Why are different environments found in each region of respiratory airways? (hint: particle size)
Upper airways trap large particles, smaller particles reach lower airways
How does water solubility of inhaled gases affect region of toxicity?
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
Mechanisms of deposition: what is impaction?
Particles are deposited because blocked by a bifurcation point
Mechanisms of deposition: what is interception?
Particle trajectory brings it into contact with airway epithelium (large airways)
Mechanisms of deposition: what is sedimentation?
Due to gravity, flow diminishes, leading to sedimentation (small airways)
Mechanisms of deposition: what is diffusion?
No more flow, just random Brownian motion and eventually deposit (alveoli)
What are some natural mechanisms to protect in acute lung injury?
Breath holding –> trigeminal nerve
Bronchoconstriction –> vagus nerve
What are the potential effects of acid/alkali toxicants?
Cell necrosis –> increase permeability of alveolar wall –> pulmonary oedema decreases gas exchange
What are the beneficial and harmful effects of ROS produced by the host?
ROS is part of host defence and aims to kill invading microbes. However if excessive will damage lung.
What are the two chronic lung toxicity responses? Briefly outline their characteristics.
Emphysema: absence of fibrosis, destruction of gas exchange surface so creates big empty lungs.
Fibrosis: increased collagen deposition, lungs go stiff
Name causes of emphysema
Smoking (mainly), cadmium oxide
Does emphysema exhibit increased or decreased compliance?
Increased compliance (ability of lung to stretch and expand) due to reduced exchange surface.
What is the effect of reduced flow/movement in emphysema?
Air trapping
What causes emphysema?
Smoking reduces activity of alpha1 anti-protease. Causes diffuse destruction of alveolar and bronchiolar walls.
In fibrosis, which type of collagen increases?
Type 1 collagen, is more stiff
Does emphysema cause decrease/increase of vital capacity, and decrease/increase of reserve volume?
Increases vital capacity (more space in lungs due to destruction of walls), increases reserve volume (lungs not collapsing properly, cause air trapping)
Does fibrosis cause decrease/increase of vital capacity, and decrease/increase of reserve volume?
Decreases vital capacity (more collagen takes up space), decreases reserve volume.
