PULMUNOTOXICITY

[RESPIRATORY
TOXICITY]
LECTURER : MISS JUNAIDAH ZAKARIA

MISS NUR SYAFIQAH FAUZAN

 LUNG
 Functions
 Gas exchange
 Biotransformation of xenobiotic
 Toxicity due to
 Efficient absorbing many type of inhaled materials
 Functional
 Biochemical
 Morphology
 Structure
 Major division – 22
 Cell type – 40
 Lung function test
 Lung volume
 Mechanical behaviour of the lung
 Gas exchange proficiency
Figure 1 : Schematic
representation of the subdivisions
of the conducting airways and
terminal respiratory units.
(Reproduced with permission from E. R. Weibel,
Morphometry of the Human Lung, Springer-Verlag, New
York,
1963.)
HEALTHY LUNG
LUNG IN DISEASE
LUNG CELLS

• Ciliated epithelium
• Nonciliated bronchiolar epithelium (Clara cells)
• Type I pneumocyte (sq. alveolar)
• Type II pneumocyte (great alveolar)
• Alveolar macrophage
• Vascular epithelium
• Interstitial cells (fibroblast and fibrocytes)
 TERMINOLOGY
• Aerosols
• Dust
• Fume
• Smoke
• Mists
• Fog
• Irritants – produce inflammation in the mucus membrane
• Asphyxiant – materials deprive the body O2
• CO – interfere with transport of O2 to the tissues by its affinity for Hb
• Cyanide – alter cellular use of O2 in energy production
ABSORPTION & DISTRIBUTION

• Concentration in the inhaled air

• Duration of exposure
• Solubility
• Level of physical activity
AEROSOL CHARACTERIZATION
AND BEHAVIOUR

• Particle size
• Deposition mechanism
• Interception – depend on fibre length
• Impaction (at nasopharynx) – diameter
• Sedimentation – deposition in the smaller bronchi and alveolar
• Diffusion – deposition of submicron particles
 SITE OF RESPIRATORY TRACT
DEPOSITION AND EFFECTS

• Water solubility
• High – upper airways eg NH3, formaldehyde
• Moderate – lower airways eg. Cl2 , SO2
• Low – lung parenchyma eg. N2, Oxides, Phosgene

• Particles size
• > 10 micron - upper airways
• eg. Dust from earth crust
• 2.5 – 6 micron – lower airways
• eg. Some fire smokes particles
• < 2.5 micron – lung parenchyma
• eg, metal fumes, asbestos fibre
 RESPIRATORY TRACT
DEFENSE MECHANISM
• Non specific
• Clearance – nasal, tracheabronchiol, alveolar
• Secretion – mucus, surfactant
• Celullar defense
• Nonphagocytic – epithelium
• Phogocytic – macrophage & neutrophils
• Biochemical defense
• Antiproteolytic enzymes
• antioxidant
 RESPIRATORY TRACT
DEFENSE MECHANISM
• Specific (immunologic) defense
• Antibody-mediated (B lymphocytes)
• Serum immunoglobulin
• Secretory immunoglobulin
• Cell-mediated (T Lymphocytes)
• Lymphokines mediated
• Direct cellular cytotoxicity
CURRENT AND NEW CHALLENGES IN
OCCUPATIONAL LUNG DISEASES
 POTENTIAL EFFECTS OF
INHALED IRRITANTS
Site of injury Acute Chronic
Eye, nose, sinus, oropharynx Irritation Corneal scarring
Inflammation Nasal polyp

Upper airways Laryngeal oedema Laryngeal polyp

Upper airways obstruction

Lower airways Tracheabronchitis Asthma

Bronchorrhea Bronchiectasis
Decrease mucociliary
clearance
Lung parenchyma Pneumonitis Pulmonary fibrosis
Pulmonary oedema Bronchiolitis obliterans
Acute respiratory distress
syndrome (ARDS)
 PULMONARY EFFECT
1. Local irritation eg.Amonia, Chlorine, Arsenic
Bronchial constriction & oedema

2. Cellular damage & oedema

Ozone & oxides of nitrogen - Peroxidation of cell membrane
Perchloroethylene & xylene – reenter from blood system by forming
reactive intermediate bind covalently with macromolecules

3. Fibrosis – damaged macrophages release factors stimulate the

fibroblast & the formation of collagen (eg silica, abestos, ETS)
4. Allergic response – bronchoconstriction triggered by the
reaction between ag-ab
5. Lung Cancer
CHRONIC PULMONARY INJURY
• Occurs when defense mechanism & repair
processes cannot resolve damage
• Acute exposure to high concentration
• Repeated exposure to low level

• Outcome of struggle between repair and injury

• Chronic obstructive pulmonary disease (COPD)
• Fibrotic restrictive Diseases – asbestos, silica
• Cancer – asbestos, Bis(chloromethyl)ether (BCME), Ni, Cr, Be
 CHRONIC OBSTRUCTIVE PULMONARY
DISEASE (COPD)

• Emphysema – destruction of the walls of the air space

distal to the terminal bronchioles resulting in the AbN
permanent enlargement of the air space
• Inflammatory
• Imbalance in the levels of protease and antiprotease in the lung

• Chronic Bronchitis – excessive mucus secretion in the

bronchial tree and a chronic or recurrent productive
cough
• Bronchial asthma – increase responsiveness of
airways smooth muscle

Watch video:
https://www.youtube.com/watch?v=TEuSV_7gWA8
 BRONCHIAL ASTHMA

• Nerve cell stimulation

• Airways inflammation (mediated by
cytokines)
• Oedema
• Epithelium permeability
• Mucus secretion
• Vascular permeability

• Airways obstruction & hyperresponsiveness

 BRONCHIAL ASTHMA

• Diisocynate – reactive because of the presence

of –N-C-O gp easily reactive with biological
molecules & potent irritant to respiratory tract
• Vegetables dust – direct release of histamine
and contain endotoxin induce inflammatory
response
• Metal salt – eg Platinum – specific IgE antibody to
platinum
• Ni, Vd, Cr, Co

• Acid anhydrides eg phthalic – specific IgE

(allergen-specific immunoglobulin) antibody
Watch the video:
https://www.youtube.com/watch?v=VDOJF2YqQnw
LUNG CANCER

• Asbestos – cancer promoter

• Arsenic -
• Chloromethyl ethers –alkylating agent capable of
causing DNA damage
• Chromium (hexavalent)
• ETS
• Nickle
• PAH (benzo-[a]-pyrene)
• Radon – inert gas product of Uranium-235.