toxic responses of the lung

Toxic responses of the lungEnvironmental health and toxicology – Lecture 7

Lecture Objectives

• Understand the function of respiratory system

• State natural mechanisms against airborne hazards

• Be aware of occupational lung diseases• Understand occupational airborne

hazards• Understand health effects linked to PM• State mechanism involved in causing PM-

related health effects

Content

• Respiratory system• Stages of lung toxic responses• Workplace exposures• Occupational lung diseases• Air borne hazards• Smoking • Air pollution• Particulate Matter

Quiz

• What is the body's main method to remove dust, mucus, saliva, and other debris from the lungs?

• Coughing!

• But inability to cough can lead to infection. Deep breathing exercises may help keep finer structures of the lungs clear from particulate matter, etc.

Words: mucus 粘液 , saliva 唾液 , debris 碎片

Respiratory System

• No oxygen -live only minutes • Every cell needs constant

supply of oxygen• Lungs link to supply of life-

giving oxygen

Respiratory System

• Normal breathing – online flash http://www.airinfonow.org/html/lungattack/lungplay.htm

Lung anatomy

Words: trachea 气管 , cartilage 软骨 , pharynx 咽 , larynx 喉

Lung anatomy

• The blind sacs in the lung tissue, called alveoli, consist of several types of cells. Each alveolus has a network of capillaries that carry blood in the lungs.

Lung anatomy

the largest, thin cells that form the walls, or septa, of the alveoli.

line the alveoli and secrete a substance called "surfactant." Surfactant coats the alveoli and provides pressure to keep them from collapsing. Without surfactant the alveolar surfaces tend to stick together which causes the alveoli to collapse.

scavenger cells that work to keep the lung free of "foreign" materials.

part of the connective tissue in the lungs.

巨噬细胞

II 型肺泡上皮细胞

I 型肺泡上皮细胞成纤维细胞

毛细管

Development of the alveoli

Time of Development

Structures that Develop

0-5 week old embryo

major airways (trachea, bronchi) form

5-16 week old embryo

bronchi branch and subdivide

16-26 week old embryo

lung cells differentiate into different cell types

26 week old embryo - birth

airways expand and grow

1-2 year old baby alveoli form by the formation of additional septa

Lung volume

潮气量肺总容量

补吸气量

补呼气量

余气量

功能余气量

肺活量

Tidal breath

• Tidal breathing is the inhalation and exhalation method by which mammals breathe.

• It refers to the amount of air used when at rest and when breathing functions are automatic.

• It is measured by doctors trying to study or diagnose respiratory and other health problems.

Natural mechanisms against airborne hazards

• Fine hairs in nose– front-line barrier – filter– exercise/hard work

• Cough reflex – clears trachea & main bronchi

• Special cells – destroy bacteria & viruses• Ciliary cells – few hours to expect foreign

material• Innermost areas of lungs – much longer to

clear outWords: Cilia 纤毛

Respiratory System

• Lungs that receive prolonged &/or repeated exposure to air contaminants eventually cannot keep up with the rate of deposition &/or constant irritation.

• Result: contaminants accumulate contributing to the development of Occupational Lung Diseases.

Diagram- black asbestos fibers- exposure standards to be less than 1 fibre/cm3 for 8 hr exposure.

Stages of lung toxic responses

• Stage 1 Exposure through inhalation• Stage 2 Action of agent on component of the

cell starting with binding• Stage 3 Response of lung to loss of function • Stage 4

Transport of agents to other sites of action

• Toxic actions are based on four factors:– Pattern of inhaled exposures– Ability of the agent to bind to

cellular components– Capacity for cellular repair– Capacity to detoxify the agent and

excrete from the body.

Disorders of the respiratory system

• Obstructive conditions 阻碍性肺病• Restrictive conditions (interstitial

lung diseases) 限制性肺病• Vascular diseases 肺血管疾病• Infectious, environmental diseases

感染性肺病

Obstructive conditions

• diseases of the lung where the airways (i.e. bronchi, bronchioles, alveoli) become reduced in volume or have free flow of gas impeded, making it more difficult to move air in and out of the lung.

• e.g., emphysema, bronchitis, asthma

Words: emphysema 肺气肿 , bronchitis 支气管炎 , asthma 哮喘

Restrictive conditions

• a loss of lung compliance, causing incomplete lung expansion and increased lung stiffness.

• e.g., fibrosis, sarcoidosis, alveolar damage, pleural effusion

Words: fibrosis 肺纤维化 , sarcoidosis 肺结节病 alveolar damage 肺泡损伤 , pleural effusion 肺积水

Vascular diseases

• describes any condition that affects the blood circulation in the lungs.

• e.g., pulmonary edema, pulmonary embolism, pulmonary hypertension

Words: pulmonary edema 肺水肿 , pulmonary embolism 肺栓塞

pulmonary hypertension 肺高压

Infectious diseases

• communicable diseases, or contagious diseases comprise clinically evident illness resulting from the infection, presence and growth of pathogenic biological agents in an individual host organism.

• e.g., pneumonia, tuberculosis, asbestosis, particulate pollutantsWords: pneumonia 肺炎 , tuberculosis 肺结核 , asbestosis 石棉沉着病

The Spectrum of Lung Disease

Chronic Obstructive Pulmonary Disease慢性阻塞性肺疾病

鼻炎

Restrictive lung disease

喉炎

Soreness of the throat

扁桃体

Bronchitis

Chronic or acute inflammation of the mucous membrane of the bronchial tubes.

Emphysema

•A pathological condition of the lungs marked by an abnormal increase in the size of the air spaces, resulting in laboured breathing and an increased susceptibility to infection.

•It can be caused by irreversible expansion of the alveoli or by the destruction of alveolar walls.

Asthma

• A chronic respiratory disease, often arising from allergies, that is characterised by sudden recurring attacks of laboured breathing, chest constriction, and coughing.

Pulmonary Edema

• Pulmonary Edema is Abnormal fluid accumulation within the alveoli and the interstitial tissues of the lungs.

Occupational health trends

• Occupational lung diseases:– workplace exposure to irritating or

toxic substances- may cause acute or chronic respiratory ailments.

Occupational lung diseases

• Occupational Asthma• Reactive Airways Dysfunction

Syndrome (RADS) 反应性气道功能障碍综合征 (asthma-like syndrome developing after a single exposure to high levels of an irritating vapour, fume, or smoke. )

• Emphysema• Chronic Bronchitis (repeated

infections and/or exposure to irritants such as fumes/dusts, oil aerosols, gases, smoke)

Occupational lung diseases

• Pneumoconiosis (PM 5μm)• Hypersensitivity Pneumonitis

(organic dusts-fungi, animal proteins, vegetable proteins)

• Granulomatous Disease (TB, toxins-Berylliosis best known occupational example)

Words: Pneumoconiosis 肺尘症 , Hypersensitivity Pneumonitis 过敏性肺炎

Granulomatous Disease 肉芽肿病 , Berylliosis 铍尘肺

Occupational lung diseases

• Pneumonia – toxic process or more commonly infections (health care, child care & animal care workers) – fungi, bacteria, viruses, other microorganisms

• Occupational Lung Cancer – smoking, coal tar, pitch volatiles, mustard gas, arsenic, asbestos, radium, petroleum, chromates, uranium

Pneumoconiosis

• Depending upon the type of dust, the disease is given different names:– black lung coal, carbon– Asbestosis asbestos– Silicosis silica– Bauxite fibrosis bauxite– Berylliosis beryllium– Siderosis iron– Byssinosis cotton– Silicosiderosis mixed dust

containing silica and iron

Acute respiratory irritation

• It results from the inhalation of chemicals:– Ammonia, chlorine, nitrogen oxide in

the form of gases, aerosols• If such irritants reach the lower

airways it damage the alveoli’s & pulmonary edema may occur

• Although the effect of irritants are usually short lived, some may cause chronic alveolar damage or airway obstruction.

Occupational lung hazards

• Classification of work hazards– Physical– Mechanical– Chemical– Biological– Psychosocial

Hazard and Risk

• Hazard– potentially harmful

• Risk– probability of harm– (quantifiable as risk

assessment)

Airborne hazards

• Mineral dust• Organic dust• Chemical dust• Fumes• Mists & sprays• Vapours• Radiation• Biological hazards

Airborne hazards – Mineral dust

• Dusts & mineral fibres from stones, rocks, ores

• Sources– Mining, quarrying, tunnelling, blasting,

smelting, grinding, milling, processing, drilling, abrading

• Industries– mines, quarries, foundries

• Lung effects– pneumoconiosis (asbestosis, silicosis, black

lung) chronic bronchitis, emphysema, fibrosis, cancer

Airborne hazards – Organic dust• Dusts formed from living materials-

micro-organisms, plants, animals & natural products like wood & leather.

• Sources– Wood, cereal grains (planting, harvesting,

storing, transporting, processing), animal husbandry (droppings, dander, feathers)

• Industries– Agriculture, manufacturers (furniture/

drugs), millers, bakers, chemists• Lung effects

– Hypersensitivity reactions-occupational asthma or hypersensitivity pneumonitis-permanent obstructive disease, diffuse lung fibrosis. Wood dusts -cancer

Airborne hazards – Chemical dust

• Synthetic chemicals (powder form), such as pesticides, pharmaceuticals, dyes, bleaching agents, detergents, paints

• Sources– Any contact from making, packaging,

applying, weathering

• Industries– aircraft building, pulp mills, chemical,

breweries, foundries, hairdressing, health care, labs, manufacturing (paints), paint sprayers

• Lung effects– Depends on toxic properties of specific

chemicals-irritants, allergens, cancer

Airborne hazards – Fumes

• Very small solid particles formed when hot vapours cool rapidly & condense– Can give off hazardous gases– Act like very fine mineral dust in lungs

• Sources– High heat processes

• Industries– Smelting, arc-welding, furnace work

• Lung effects– Difficult to assess effects of separate

materials since several hazards present at same time. Can lead to emphysema & lung cancer.

Airborne hazards – Mists & sprays

• Liquid droplets suspended in air or other propellant gas.

• Sources– Cleaning products, pesticides, paints,

cosmetic products, rust removers

• Industries– Cutting, grind, spraying and pickling

operations, electroplating

• Lung effects– The finer the spray, the deeper into the lungs

it goes. Effect depends on material, concentration and temperature.

Airborne hazards – Vapours

• Vapours hang out with parent liquid• Sources

– Inorganic-high boiling points, don’t vaporise at room temperature-aren’t usually associate with lung disease

– Organic-many vaporise at room temperature-used as solvents (ketones, alcohols, acetates, aromatic hydrocarbons)

• Lung effects– enter body through lungs– damage to other organs more so than lungs– pulmonary edema & tracheobronchitis.

Airborne hazards – Radiation

• Radiation– Non-ionising radiation (electromagnetic waves-

infrared, ultraviolet, microwave, laser, radar, radio frequency)

– Ionizing radiation (alpha, beta, gamma rays, neutron particles & x-rays)

• Sources– Mining radioactive ores

• Industry– Medicine, power plants, equipment used in industry

(high energy electrical equip., lasers, microwaves, radar)

• Lung effects– Electromagnetic waves can cause thermal burns.

Ionising radiation can cause cancer.

Airborne hazards – Biological hazards

• Bacteria, viruses, fungi• Sources

– Health care & child care facilities, poorly maintained ventilation systems, biological research labs, animal care & processing facilities

• Lung effects– Depends on type of hazard. Can be

minor allergies & lung infections to cancer. Vaccinations for some.

Smoking

• Smoking contributes to lung disease– Impairs lungs’ natural defense

mechanisms –irritates airways & inhibits work of ciliary cells

– Oxidants are one toxic component of cigarette smoke. They can damage the DNA of lung cells much like the sun damages skin cells.

Smoking

• Smoking is leading cause of serious lung disease & certain types of cancer– Synergistic effect with other pulmonary

carcinogens (asbestos, chromium/uranium compounds, arsenic)

– Increases lung cancer risk

• Smokers develop lung disease & cancer more readily & diseases progress more rapidly

Air pollution

• Air pollution may be defined as the presence in the air (outdoor atmosphere) of one or more contaminants or combinations thereof in such quantities and of such durations as may be or tend to be injurious to human, animal or plant life, or property, or which unreasonably interferes with the comfortable enjoyment of life or property or conduct of business.

Who is at risk?

• Everyone faces increased risk of harm from exposure to these hazardous air pollutants.

• Particularly:– Children and teenagers;– Older adults;– Pregnant women;– People with asthma and other lung diseases;– People with cardiovascular diseases;– Diabetics;– People with low incomes;– People who work or exercise outdoors; and– Others with existing health problems

Industrial Toxicants that Produce Disease of the Respiratory Tract

Fine particles, or haze, restrict our

ability to see long distances

HartfordOct. 8, 20024 p.m. EDT

Unadjusted Hourly conc. of fine particles – 4 g/m3

HartfordOct. 2, 20024 p.m. EDT

Unadjusted Hourly conc. of fine particles – 24 g/m3

“ Bad” Air Quality

• Ozone• Particulate Matter• Nitrogen Dioxide• Sulfur Dioxide• Hazardous Air Pollutants (Toxins)• Carbon Monoxide

The ozone storyGood Ozone – Protect us from UV light

Bad Ozone

• Ground-level or "bad" ozone is not emitted directly into the air, but is created by chemical reactions between oxides of nitrogen (NOx) and volatile organic compounds (VOC) in the presence of sunlight. Emissions from industrial facilities and electric utilities, motor vehicle exhaust, gasoline vapours, and chemical solvents are some of the major sources of NOx and VOC.

Ozone pollution basics

Lung attack – Ozone http://www.airinfonow.org/html/lungattack/lungplay.htm

Particulate Matter matters

• Particulate matter (PM) is a complex mixture of organic and inorganic substances.

Image from http://www.epa.gov/eogapti1/ module3/distribu/distribu.htm

• PM pollution consists of materials (including dust, smoke, and soot), that are directly emitted into the air or result from the transformation of gaseous pollutants.

PM

Where Does PM Originate?

VOCs

NO2

SO2

• Particles come from natural sources (e.g., volcanic eruptions) and human activities such as burning fossil fuels, incinerating wastes, and smelting metals.

• Sources may emit PM directly into the environment or emit precursors such as sulfur dioxide (SO2), nitrogen dioxide (NO2), and volatile organic compounds (VOCs), which are transformed through atmospheric chemistry to form PM.

Ammonia (NH3)

Ammonia (NH3)

Sources of PM and PM Precursors

Mobile Sources(vehicles)

VOCs, NO2, PM

Stationary Sources (power plants, factories)

NO2, SO2, PM

Area Sources(drycleaners, gas

stations)VOCs

Natural Sources (forest fires, volcanoes)

PM

The Role of Inversions

An inversion is an extremely stable layer of the atmosphere that forms over areas. Temperature inversions trap pollutants close to the ground. These inversions involve layers of hot air sitting above cooler air near ground level. When particles accumulate in the air layer, they are unable to rise into the atmosphere where winds will disperse them.

Source: http://www.epa.gov/apti/ course422/ ce1.html

PM10 & PM2.5

• Particles found in ambient air range in size from a few nanometres (nm) to several hundred micrometres (μm) in diameter.

• PM10 refers to the mass concentration (expressed in μg m–3) of particulate matter that is generally less than 10 millionths of a metre (10 μm) in diameter.

• PM2.5 refers to the mass concentration of particles less than 2.5 μm in diameter.

Particulate Matter: Size Matters

• Particles larger than 10 μm are trapped in the nose and throat and never reach the lungs.

• Particles 10 μm in diameter or less are of most concern for their effects on human health.

Image: PM2.5. By D. Hershey. From New York State Department of Environmental Conservation. http://www.dec.state.ny.us/website/dar/baqs/micro/two.html

• Particles between 5 and 10 μm are removed by physical processes in the throat.

• Particles smaller than 5 μm reach the bronchial tubes.

• Particles 2.5 μm in diameter or smaller are breathed into the deepest portions of the lungs.

PM2.5

• Lung attack – PM2.5 http://www.airinfonow.org/html/lungattack/lungplay.htm

London, 1952

Great smog - London

What Adverse Health Effects Have Been Linked to PM?

• Premature death• Lung cancer• Development of chronic lung

disease• Heart attacks• heart and lung disease• Decreased lung function• Pre-term birth• Low birth weight

Source:http://www.nasa.gov/topics/earth/features/health-sapping.html

Global satellite-derived map of PM2.5 averaged over 2001-2006

Increasing Evidence of Cardiovascular Effects

Until the mid 1990s, most research focused on the association of PM exposure with respiratory disease. Since then, there has been growing evidence of cardiovascular health effects from PM.

Integrating Toxicology, Epidemiology and Clinical Studies• Toxicological, clinical and

epidemiological studies have increased understanding of the mechanism of action by which PM leads to mortality and lung and heart disease.

Toxicology, Epidemiology and Clinical Studies

• At right are stained photomicrographs of abdominal arteries from mice exposed to filtered air and air polluted with fine particulate matter, with the increased arterial blockage in the PM-exposed mice providing scientific support for the link between PM and atherosclerosis found in a study of human subjects (Kunzli et al., 2005). Sun et al. JAMA, 2005

Several theories have been advanced as to the mechanism of action. It is likely that more than one mechanism is involved in causing PM-related health effects. Theories include the following:

4. PM causes inflammation of lung tissue, resulting in the release of chemicals that impact heart function;

5. PM causes changes in blood chemistry that results in clots that can cause heart attacks.

1. PM leads to lung irritation which leads to increase permeability in lung tissue;

2. PM increases susceptibility to viral and bacterial pathogens leading to pneumonia in vulnerable persons who are unable to clear these infections;

3. PM aggravates the severity of chronic lung diseases causing rapid loss of airway function;

How Does PM Cause Health Effects?

Air Quality Index

• The purpose of the AQI is to help you understand what local air quality means to your health.

Freddy

How to use the AQI

Step 1 Determine whether you (or your family) are likely to be at risk from air pollution.

Step 2 If you may be at risk, and are planning strenuous activity outdoors, check the air pollution forecast.

Step 3 Use the health messages corresponding to the highest forecast level of pollution as a guide.

Air Quality Index (UK)

Source:http://www.comeap.org.uk/images/stories/Documents/Reports/comeap%20review%20of%20the%20uk%20air%20quality%20index.pdf

Health Advice to Accompany the Air Quality Index

Enjoy your usual outdoor activities.

At-risk individuals should consider reducing strenuous physical activity, particularly outdoors.General population could enjoy usual outdoor activities.

Health Advice to Accompany the Air Quality Index

At-risk individuals should reduce strenuous physical exertion, particularly outdoors, and particularly if they experience symptoms. People with asthma may find they need to use their reliever inhaler more often. Older people should also reduce physical exertion.Anyone experiencing discomfort such as sore eyes, cough or sore throat should consider reducing activity, particularly outdoors.

Adults and children with lung problems, adults with heart problems, and older people, should avoid strenuous physical activity. People with asthma may find they need to use their reliever inhaler more often.Reduce physical exertion, particularly outdoors, especially if you experience symptoms such as cough or sore throat.