Respiratory Toxicology

Transcription

1 Respiratory Toxicology Loch-Caruso ENVIRON

2 Breathing Oxygen Carbon Dioxide Loch-Caruso ENVIRON

3 Breathing Enlarged view of the airways, alveoli (air sacs), and capillaries (tiny blood vessels) Loch-Caruso ENVIRON Close-up view of gas exchange between capillaries and alveoli 3

4 How Can Toxicants Affect Breathing? What needs to work How toxicants interfere Muscle contractions Neuromuscular toxicants Brain respiratory center Neurotoxicants Airflow Airway obstruction Gas exchange Fibrosis, decreased air sacs Loch-Caruso ENVIRON

5 Respiratory Failure Characterized by inadequate oxygen supply Decreased oxygen content in arterial blood with normal oxygen capacity and blood flow Causes of respiratory failure Central nervous system depression Narcotics Chloroform Respiratory muscle arrest Organophosphate insecticides, e.g., parathion Botulinum toxin Loch-Caruso ENVIRON

6 Respiratory Failure Characterized by inadequate oxygen supply Decreased oxygen content in arterial blood with normal oxygen capacity and blood flow Respiratory muscle arrest Organophosphate insecticides, e.g., parathion Botulinum toxin Central nervous system depression Narcotics Chloroform Loch-Caruso ENVIRON

7 Restriction of Airways Flow of respiratory air is directly related to crosssectional area of passageways (Poiseuille s law) Flow is highly impacted by the airway opening (inversely related to the radius 4 ) Airways are restricted by Fluid & mucus accumulation Bronchial muscle constriction Loch-Caruso ENVIRON

8 Chronic obstructive pulmonary disease (COPD) COPD is one of the most common lung diseases There are two main forms of COPD: Chronic bronchitis, which involves a long-term cough with mucus Emphysema, which involves destruction of the lungs over time Most people with COPD have a combination of both conditions Loch-Caruso ENVIRON

9 Chronic obstructive pulmonary disease (COPD) 3 rd leading cause of death in the USA Bronchitis Emphysema Loch-Caruso ENVIRON

10 Chronic Bronchitis Loch-Caruso ENVIRON

11 Cigarette smoking is the leading cause of COPD smokerslungs.net O. Auerbach, Visuals Unlimited Loch-Caruso ENVIRON

12 Any Airway Irritant Can Contribute to COPD Air pollutants Sulfur dioxide Nitrogen dioxide Particulate matter Ozone Dust from cotton fibers, coal, silica Loch-Caruso ENVIRON

13 Airway Constriction Due to contractions of muscles surrounding airways Usually an inflammatory response Loch-Caruso ENVIRON

14 Asthma Asthma is a chronic inflammatory disease of airway constriction Usually associated with sensitization to various allergens Pollen Animal dander Toluene diisocyanate (TDI) Molds Air pollutants And more. Loch-Caruso ENVIRON

15 Inflammation is a nonspecific type of immune response Initiated by secretion of signaling molecules (chemokines) which then attract white bloods cells to site of injury Specialized white blood cells become activated at the site of injury Normal Inflammation Macrophages Neutrophils Loch-Caruso ENVIRON

16 White blood cell responses Phagocytic activity Secretion of signaling molecules Vasoactive amines (e.g., histamine) Cytokines Reactive oxygen species Prostaglandins Clotting & scarring peptides (e.g. fibrinogen, fibrin) Loch-Caruso ENVIRON

17 Lung inflammation Injury to lung initiates inflammatory response Activation of alveolar macrophages Recruitment of neutrophils Progressive inflammation leads to scar tissue formation (fibrosis) and breathing difficulties Decreases elasticity of lungs Increases thickness of lung epithelial barrier Loch-Caruso ENVIRON

18 Pulmonary Fibrosis Loch-Caruso ENVIRON

19 Lung inflammation Examples that can lead to fibrosis Particulates Cigarette smoke Asbestos Silica Coal dust Cotton dust Beryllium 143/gs033008/ Streptococcus pneumonia (bacteria) Tobacco/SecondHandSmoke/SecondHa ndsmokefacts.htm Loch-Caruso ENVIRON

20 Pneumonia Usually caused by microorganisms Also caused by inhalation of highly destructive toxicants Methyl isocyanate disaster in Bhopal, India (1984) Ammonia Perchloroethylene h/healthtopics/topics/pnu/causes.html Loch-Caruso ENVIRON

21 Preterm Birth Babies born preterm have Underdeveloped lungs Increased risk for bronchopulmonary dysplasia, a chronic lung disease caused by respirator use with infants Increased risk for respiratory distress, the single most common cause of illness and death in preterm infants Loch-Caruso ENVIRON Increased risk for lung disease from cigarette smoke as adults 21

22 Lung Cancer serbagunamarine.com Loch-Caruso ENVIRON