15 - Lung tox Flashcards
(35 cards)
Why is the lung susceptible to toxicity?
- Contact w/ enviro
- Sample LARGE vol. of air
- Exposed to blood direct from R Ventricle
Inhaled toxicants can have two effects
- Local: Nasal, Upper and Lower airways
- Distant: toxin abs. in body, toxic effects on distant organs
Lung toxicants have two sources
- Inhalation
- From blood supply (e.g. Paraquat, pesticide)
Nasal function
- Heats and humidifies air
- Filter (large particles)
- Epithelium has CYP
Respiratory Tract Anatomy
- Nasal cavity
- Naso-pharynx
- Oropharynx
- Pharynx
- Larynx “voice box”
- Trachea “windpipe”
- Airways
- Alveoli “gas exchanging units”
Airway branching
~27 generations of asymmetrically branching airways
* R Lung - 3x lobes
* L Lung - 2x lobes
Lung Histology - Conducting Portion
Pseudostratified ciliated columnar
* Goblet = mucus
* Mucous glands underneath
Lung Histology: Air-Sacs (Alveoli) Terminal Portion
- Type I pneumocytes: line the air-sacs (95% SA), thin, gas exchange
- Type II pneumocytes: located in corner of alveoli (5% SA), prod. surfactant
What does surfactant do?
Detergent that reduces surface tension so that alveoli remain open
Lung tox and Type II cells
Type II cells can transform to Type I when Type I are damaged
Mucus
Goblet and mucous glands produce mucin
* Mucin + Water = Mucus
* Host defense
Mucociliary System
Cilia beat/propel mucus out of lungs
* Get rid of things that you breathed in
Mucus: Direction of Flow
- Nose is backwards (Down ➔ swallowed)
- Trachea & lower airways go upwards (Mucus and “loaded-up” macrophages ➔ Swallowed or expectorated)
Air velocity and directional change in airway
Both decrease as we go deeper
* Upper - Inertial impaction, change direction abruptly
Particle size in each region
- Larger particles trapped higher
- Nanoparticles more likely deposited in alveolar region
Site of injury depends on water solubility
- Highly soluble (e.g. SO2) captured in nasal fluid, not vry tox
- Relatively water insoluble (e.g Ozone, NO2) penetrate deep into lung, small airway/alveolar damage
- Very water insoluble (e.g.CO) reach alveoli and penetrate, blood, tissue hypoxia
Anaesthesia
Use FA (alveolar conc.) as a surrogate for [anesthetic]brain
* FA(alveolar conc.) / FI(inspired conc.)
* Conc. is Partial Pressure
* Equilibirm is acieved quickly in anesthetics with high Log P (less soluble in blood)
Mechanism of deposition
- Impaction (@ sites of bifurcation in large airways)
- Interception (particle trajectory ➔ contact with large airway epithelium)
- Sedimentation (flow ↓, small airways)
- Diffusion (NO flow, alveoli)
Haber’s Rule
Exposure to high conc. for short time can do same as exposure to low conc. for long time
* 𝑪 × 𝒕 = 𝒌
* C is gas conc. (g/L)
* t is time required to produce given toxic effect
* k is a constant
Acute Lung Injury
- Breath holding + behaviour (trigeminal N.)
- Bronchoconstriction (vagus N.)
- Acid or alkali toxicants ➔ ↑ permeability of alveolar wall ➔ necrosis
Ozone local effects
- Generates ROS
- Cell damage ➔ release contents
- FURTHER ROS
- Damage ➔ OEDEMA
Lung Defence Cells: Activated Macrophages
Molecular oxygen ➔ ROS
* Kill microbes (host defense) “appropriate”
* Intracellular ROS activates of phagocytic proteinase
Chronic Lung Toxicity Responses
- Emphysema (Smoking is main cause, cadmium oxide, aluminium abrasives)
- Fibrosis (Asbestos, coal dust, ozone)
Emphysema
Obstructive ➔ ⬇ gas exhange SA
* ↑ compliance and air trapping
* Caused by ↓ ⍺-1-antiprotease activity + unrestrained elastase activity
* RAMPANT breakdown
