Respiratory Toxicology Flashcards
two cell types in bronchial cells
Brush cells
Clara cells
Processes for gas exchange
ventilation
perfusion
diffusion
active expansion, passive contraction, elasticity, and constriction
ventilation
blood flow direct from heart
perfusion
affected by fluid (edema) or collagen build up
diffusion
three characteristics of pathogenesis
oxidative burden
particle deposition
particle clearance
what causes oxidative burden
ROS production from ozone, nitrous oxide, smoke, and immune cells
effects from ETC, biotransformation enzymes, respiratory burst
what determines deposition, region, and mechanism for particle deposition
particle size
mucociliary escalator removes two things…
mucous-trapped particles
loaded macrophages
acute responses in respiratory tract leads to (5)
nasal irritation reduced ventilation coughing bronchoconstriction pulmonary edema
smooth muscle action, restricts air flow
bronchoconstriction
release of fluid in alveoli, restricts diffusion
pulmonary edema
mechanisms for respiratory toxicity
biotransformation
repair mechanisms
cell signaling pathways
biotransformation causes
reduction in ROS using SOD, CAT, AND GPX
activation by phase 1/ phase 2 enzymes
repair mechanisms are abundant causing _____but, _____
few cells to die under normal conditions but type II cells can transform into type I and replace
COPD
chronic obstructive pulmonary disease
COPD causes
bronchitis and emphysema
inflammation, increased mucus, less ciliated cells, chronic cough
bronchitis
loss of alveolar structure, reduced gas exchange surface
acute toxicity emphysema
chronic responses to respiratory toxicity
fibrosis
emphysema
asthma
cancer
accumulation of interstitial collagen, lungs smaller and stiffer
fibrosis
loss of alveoli, lungs larger and less elastic, smoking, additional immune response effect
chronic response emphysema
air way constriction sensitization of immune system
asthma
tobacco smoke, fibers, metals
cancer
what are the problems with microfibers and macrophages
long fibers cannot be completely enclosed by a macrophage producing frustrated phagocytosis
causes an increase in macrophages creating an autoimmune effect
asbestosis causes
mesothelioma and lung cancer
silicosis occurs from
fibrotic nodules
macrophage ingesting particles
excretion of cytokines
induction of collagen production in fibroblasts
from hot cooking oil smoking and reactive with biomolecules (DNA)
acrolein
activation by CYP1A1 in clara cells and type II cells
naphthalene
very toxic in overdose: general oxidative damage, therapeutic
oxygen
plant alkaloid, metabolized in liver, pyrrole causes endothelial damage
monocrotaline
herbicide that inhibits photosynthesis
paraquat
how does paraquat cause toxicity
mimics specific growth factors for cell division, binds to receptors
what happens with paraquat toxicity
specific lung damage
free radical formation
irreversible lung necrosis, fibrosis, suffocation, slow painful death
deposition of particles on the airway mucosal surface is brought about by a combination of
aerodynamic forces and particle characteristics
three critical factors in determining how deeply a given gas penetrates into the lung
solubility
diffusivity
metabolism/reactivity
occurs in the upper respiratory tract and large proximal airways where the airflow is faster than the small distal airwaves
impaction
occurs when the trajectory of a particle brings it near enough to a surface so that an edge of the particle contacts the airway surface
interception
controls deposition in the smaller bronchi, the bronchioles, and the alveolar spaces, where the airways are small and the velocity of airflow is slow
sedimentation
an important factor in the deposition of submicrometer particles
diffusion
a minor deposition mechanism for positively charged particles
electrostatic deposition
confers immediate recognition, phagocytosis, and killing of bacteria and microbes that are in the airway or alveolus
innate immune system
involves dendritic cells that take up and present antigens to T lymphocytes or antibody-producing B lymphocytes
adaptive immunity
