Certain gases, vapors, and inhaled irritants can stimulate nerve endings in the nose and cause inflammation in the lungs. Prolonged exposure can lead to increased permeability of the alveolar walls and pulmonary edema. Reactive molecules like ozone can cause lesions that are propagated by secondary reactions and reactive oxygen species. Metabolism of toxins by cytochrome P450 enzymes and other cytosolic enzymes can also play a role in lung injury pathogenesis.

2. Certain gases and vapors
stimulate nerve endings in
the nose, particularly those
of the trigeminal nerve.
Holding of breath or
changes in breathing
patterns

3. Continued exposure…..
Cell necrosis
Increased permeability of the alveolar walls
Acidic or alkaline
irritants

4. Inhalation of high concentrations of HCl, NO2, NH3
or phosgene
At first, Produce very little apparent damage in the
respiratory tract
After several hours…….
Epithelial barrier on the alveolar zone begins to leak,
flooding the alveoli and producing a delayed
pulmonary edema

5. For highly reactive molecules such as OZONE….
Ozone lesions are propagated by a cascade
of seondary reaction products and by
reactive oxygen species arising from
free radical reactions

6. Metabolism can also be involved in the pathogenesis of lung
injury….
Cytochrome P450s 1A1, 2B1, 2F1, 4B1, and 3A4
NADPH cytochrome P450 reductase
Epoxide hydrolase
Flavin-containing monooxygenases.
Glutathione S-tranferases
Glutathione peroxidase
Cytosolic enzymes
involved in xenobiotic
metabolism

7. Caused by free radicals, such as Ozone, NO2,
tobacco smoke and lung defense cells
Oxidant species may mediate or promote the
actions of pneumotoxicants.
When cellular injury of any type occurs, the release
of otherwise contained cellular constituents may
lead to extracellular generation of deleterious
reactive O2 species.

8. Neutrophils, monocytes, and macrophages converts
converts molecular O2 to reactive O2 metabolites.
Toxic O2 species are released into surrounding
tissues.
Phagocytic production of active oxygen species
causes inactivation of proteinase inhibitors and
degranulation of mast cells.

9. Bronchial smooth muscles, help
maintain airway tone and
diameter during expansion and
contraction of the lung.
Bronchial smooth muscle tone,
is regulated by the ANS.

10. Bronchoconstriction can be proved by the ff:
Cigarette smoke
Air pollutants
Cholinergic drugs (acetylcholine)
Histamine
Various prostaglandins and leukotrienes
Substance P
Nitric oxide

11. Bronchoconstriction causes…
DECREASE IN AIRWAY DIAMETER
INCREASE IN RESISTANCE TO AIRFLOW
Symptoms:
Wheezing
Coughing
Sensation of chest tightness
Dyspnea

12. Represents an acute, exudative phase of lung
injury that alters ventilation-perfusion
relationships and limits diffusive transfer of
O2 and CO2 even in otherwise structurally
normal alveoli.

13. Effects of toxicants on the lung may be reversible
or irreversible.
The normal adult lung is an organ for which under
normal circumstances very few cells appear to die
and need to be replaced.
When damaged by a toxic insult, the lung
parenchyma is capable or repairing itself.

14. Type I cell damage
Proliferation of type II epithelial cells
Transform into new type I cells
In the airways……
Clara cells proliferate and divide following injury.

15. Migration of mobile blood cells such as leukocytes accross
the pulmonary capillaries into the alveolar lumen may
also trigger a mitotic response.
Capillary endothelial cells, interstitial cells, and alveolar
macrophages also proliferate.
Excessive proliferation of fibroblasts may result in lung
disease
In general, the lung appears to have a high capacity to
repair itself and thus to deal with the many toxic insults
presented by the environment.

17. Lungs become larger and too compliant, cause by
destruction of the walls without fibrosis.
Major cause: cigarette smoke inhalation, although other
toxicants elicit this response.
Toxicant induced= severe or recurrent inflammation

18. Increased amounts of collagen
Resembles adult or infant respiratory distress
syndrome
Excess lung collagen is usually observed not only
in the alveolar interstitium, but also throughout
the alveolar ducts and respiratory bronchioles.

19. Shortness of breath, caused by narrowing of
the large conducting airways.
Increased airway reactivity of the bronchial
smooth muscle in response to exposure to
irritants.

20. Potential mechanisms center on damage to DNA.
An activated carcinogen or its metabolic product
may interact with DNA.
DNA damage caused by active oxygen species is
another potentially important mechanism.
Ionizing radiation leads to the formation of
superoxide.
Cigarette smoking contains high quantities of
active oxygen species and other free radicals.

21. Uniquely sensitive to many airborne and blood-
borne toxicants.
Development of lung occurs during both the
prenatal and postnatal periods.
Stage of development during which toxicant
exposure ooccurs may greatly influence the
severity of lesion.