pneumotox - READY TO REVIEW Flashcards
t/f: there is only one type of alveolar cell
false. 2!
what affects how far a substance reaches within the respiratory tract
its solubility, its diffusivity, its metabolism and reactivity in the resp tissues, breathing rate
why don’t soluble gases make it beyond the nose (unless at very high doses)
bc they dissolve in the mucus lining
how far along the resp tract will SO2 and formaldehyde make it
not beyond the nose bc they are highly soluble
how far along the resp tract will ozone, and NO2 make it? why?
to the smallest airways and alveoli bc they are relatively insoluble
how far along the resp tract will very insoluble gases like CO and H2S make it? why?
they efficiently pass the rest tract and get taken up into the pulm blood supply – they are very insoluble
what factors affect the toxicity of inhaled materials?
blood flow, solubility, partcile size, bioactivation, absorption, site of deposition
t/f: drugs cannot be biotransformed in the respiratory tract
FALSE! there are p450s in every region
cytochrome p450 monooxygenases are most found in which region(s) of the resp tract?
the nasal tissue and the distal airway
what is the key pulmonary defense in the airways?
the micociliary elevator
what is the key pulmonary defense in the alveoli?
the macrophages
what are the three big categories of acute responses of the respiratory system to injury
airway reflexes
bronchoconstricion + airway reactivity
acute lung injury + pulmonary edema
what would trigger airway reflexes
inhaling tox chems / particles
triggers the airway receps.
what would trigger bronchoconstriction
irritiant gases that are moderately soluble trigger broncho constriction.
can prime the autonomic repsonse so the threshold for Ach mediated bronchoconstriction is lower
stimulates the irritant receps.
what happens in acute lung injury
you get damage to the alveolar epi and endothelial cells
you get activation of the NFkB response.
you get disruption of surfactant and pulmonary edema.
you get thickening of the capillary barrier and worse O2 CO2 exchange
how does nasal irritation occur (what receptors mediate this pathway)
mediated by the TRPA1 receptor!
the irritant binds to TRPA1.
this triggers firing of the trigeminal nerve
this leads to tickling, itching, nasal pain
t/f: irritants do not need bioactivation.
false. many irritants need cyp dependent bioactivation to produce the irritation. nasal tissues have lots of cyps.
where is naphthalene found? what kind of resp toxin is it?
found in dyes, resins, insectisides, cig smoke, car exhaust, smoke from forest fire
its a nasal irritant
what are the two things naphthalene needs to act as an irritant?
needs to be bioactivated by CYP.
needs to act on an intact TRPA1 receptor.
how are emphysema and resp fibrosis different? what chemicals cause them respectively?
emphysema: distended alveoli ; tobacco smoke
fibrosis; accumulation of connective tissue; asbestos.
what is COPD, and what are the 2 components it has?
its progressive airflow obstruction
has an airway component - bronchitis - and an alveolar component - emphysema
how is COPD diagnosed?
u need to have had sputum production and a cough for over 3 months in each of 2 consecutive years.
compare how a healthy and COPD lung look
copd: excess mucus, narrowed bronchioles, destruction of alveloi
t/f: COPD has no correlation with age
false! older –> more COPD
is poverty assoc with COPD? how?
yuh
more mortaility with lower nat income
t/f: emphysema is entirely separate from COPD
false.
emphysema is the alveolar component of COPD
what happens in emphysema - how is FEV 1 affected?
its airway obstruction. leads to shortness of breath. get a lower FEV1.
what happens to the alveoli/airspaces in emphysema
airspaces get BIGGER
what happens to O2/CO2 exchange in emphysema
decreases bc theres less surface area bc the air pockets merge.
describe the pathway by which emphysema occurs
the normal macrophage mediated repair mechanisms following repeated chemical insult leads to progressive emphysema.
are macrophages involved in emphysema?
YES!! they are a major contributer. experimentally, depleting the macrophages and monocytes reduces emphysema severity.
how does macrophage mediated destruction of the ECM occur (ie: how do you go from cig smoke exposure to emphysema)
cig smoke recruits inflam cells and activates them.
the t cells produce MMPs via chemokines and CD40
the smoke inactivates HDAC2–> lets NFkB trnascribe TNFa and IL8 and MMP
MMPs and elastase degrade eachothers inhibitors (TIMP and A1AT), prevents each from degrading the ECM, promotes emphysema.
are emphysema and pulm fibrosis chronic or acute lung injury
chronic
what happens to the lung structure in pulm fibrosis? how does this affect gas exchange?
the wall thickens bc of fibrotic scar tissue deposition.
disrupts gas exchange
what can trigger pulm fibrosis?
asbestos, silica, aluminum. chromium, ozone
does pulm fibrosis respond to treatment?
no! it is refractory to treatment
decribe the pathway of pulm fibrosis pathogenesis
irritants injure lung epithelial cells
these injured cells get detetcted by NALP3 inflammasome.
this leads to ROS , chemokines, cytokines
recruits leukocytes to the site of tissue injury
TGFB targets epi cells, leads to EMT, ECM producing myofibroblasts.
TGFB leads to exeserbation of immune response and differentiation of Th17 cells.
how does the alveloi repair itself after acute injury?
CRCRy promotes proliferation of AEC. this repairs the alveoli.
how does the alveoli respond after chronic injury (ie: the fibrosis mech)
VEGFR1+ perivascular macrophages gets recrutied
this initates Wnt/B catenin which upregulates Jag 1.
Jag 1 binds to and activates notch which leads to pum fibrosis.
how is braking related to irritant effect
longer braking response, stronger irritant effects
