Air pollutants may effect various systems of the body including the respiratory system, the circulatory system, and the nervous system. The respiratory system will be reviewed in this lecture.

OVERVIEW OF THE RESPIRATORY SYSTEM

Cells of the body need a constant supply of oxygen to support the following energy-generating reaction:

Food + 0₂ ------> C0₂ + H₂0 + Energy

Although the respiratory system has many functions, its primary function is to provide oxygen to the blood in order for it to be delivered to every cell of the body and to eliminate the carbon dioxide which is picked u by the blood as a waste product of metabolism.

The components of the respiratory system may be divided into the conducting portion and the respiratory or gas exchange portion. The conducting portion consists of the nose, pharynx, larynx, trachea, bronchi, secondary bronchi, bronchioles, and terminal bronchioles, all of which are important in transporting the air to the respiratory or gas exchange portion, including the respiratory bronchioles and alveoli where gas exchange occurs. A short description of the function of each of these respiratory system components follows:

Nose - In addition to possessing receptors for the sense of smell, the nose filters, warms, and moistens inhaled air. The nose is lined with epithelial cells covered with cilia and other cells which secrete mucous. These epithelial cells in combination with the connective tissue below it which contain many blood vessels are called mucous membranes.

Pharynx - During inhalation, air moves from the nose into the pharynx (throat) which functions as a passageway to the larynx (as well as to the esophagus).

Larynx - The larynx houses the vocal cords and opens into the trachea or windpipe.

Trachea - The trachea is a flexible tube lined with mucous membrane and supported on the outside by rings of cartilage which keep it from collapsing. The trachea branches into the left and right bronchi which lead into the left and right lungs.

Secondary bronchi, bronchioles, terminal bronchioles - All of these are continuous branches of the bronchi in the lungs resulting in the formation of smaller and smaller tubules.

Respiratory bronchioles and alveoli - The terminal bronchioles branch into the respiratory bronchioles which terminate in alveoli. There are 300 million alveoli which are 0.25-0.50 mm in diameter; this enormous number provides a surface area of approximately 800 square feet for diffusion of gases to occur. (This is 80x the area of human skin of an adult.) Each alveolus is only about one cell layer thick.

The alveoli are enmeshed in capillaries. These capillaries are also one cell-layer thick. The area between the alveoli and the capillaries is bathed in interstitial fluid but the actual distance separating the air in the alveoli from the blood in the pulmonary capillaries in 0.2 m. According to Sherwood (see reference below), a sheet of tracing paper is about 50x thicker than this air-to-blood barrier and it is the thinness of the barrier that facilitates gas exchange.

Basics of Gas Exchange (see reference below)

Gas exchange essentially occurs because of differences in the concentration of gases in alveoli, blood, and tissues. The concentration of a gas is measured by its partial pressure which is the amount of pressure exerted by the gas. Atmospheric pressure is the sum of all the partial pressures of the gases that comprise the atmosphere. Gases dissolved in liquids also have partial pressures and gases diffuse from areas of high to areas of low partial pressure.

The partial pressures of air and carbon dioxide in the alveoli differ from those in the bloodstream. Air which has been inspired and just arrived in the alveoli has a relatively high partial pressure of oxygen and a very low partial pressure of carbon dioxide. If you recall, during circulation of blood through the heart, the blood in which the oxygen content has become partially depleted and the carbon dioxide content has increased as a result of tissue metabolism, returns to the right atrium of the heart. After entering the right ventricle, the blood is pumped into the pulmonary arteries to the lung. Because the air in the alveoli has a high partial pressure of oxygen but the oxygen carried in the blood has a low concentration of oxygen, oxygen diffuses from the alveoli into the blood. The reverse is true for carbon dioxide and thus it diffuses from the blood into the alveoli. Unlike the lungs, the opposite occurs in the tissues, because blood leaving the heart is high in oxygen and low in carbon dioxide while oxygen is low in the tissues but high in C0₂ (as a result of cellular metabolism). Thus, in the tissues oxygen diffuses from the blood into the tissues while carbon dioxide leaves the tissues and diffuses into the bloodstream.

It should be noted that oxygen is carried in the hemoglobin of red blood cells in the blood. Each hemoglobin molecule contains four polypeptide chains and each chain is folded around a heme molecule (an iron-containing group). It is the iron that forms the loose association with oxygen. Each hemoglobin molecule can bind up to four oxygen molecules and because there are about 250 million hemoglobin molecules in each red blood cell, each cell is capable of carrying more than one billion molecules of oxygen. Most of the carbon dioxide is carried in the blood in the form of bicarbonate ion. (See references below for further discussion.)

MECHANICS OF BREATHING

Inspiration, or breathing in, is initiated by the contraction of two muscles. The diaphragm contracts and moves down while the external intercostals contract moving the ribs up and out; both actions increase the size of the thoracic cavity. Other actions (not discussed here) result in an expansion of the volume of lungs and alveoli. As a result, the air pressure in the lungs becomes lower than atmospheric pressure and air from the atmosphere rushes into the lungs. During expiration, the muscles relax, the rib cage moves down and the diaphragm moves up. When the lung volume decreases, pressure in the lungs increases and air is forced out of the lungs.

Defense Mechanisms of the Respiratory Tract We inhale 10,000-20,000 liters of air each day. Many defenses are in place to cleanse this air from pollutants as well as destroy pathogenic organisms.

In general, the size of inhaled particles determines where they are deposited in the respiratory tract. Most particles are trapped by nasal hairs or in the nose or throat, while smaller particles may reach the bronchi. All of these particles are trapped by the mucociliary tree which consists of mucous membranes and ciliated epithelial cells which line the upper respiratory tract. The mucous traps the microorganisms and pollutants and the cilia sweep them to the nasal or oral cavity where they are expelled by coughing or swallowing.

Particles that are <2.5 m in diameter are able to be deposited in the alveoli. Macrophages in the lungs help remove these organisms.

Unfortunately, these defenses are not always successful. Part of the problem is that the air pollutants can decrease the action of the cilia or at higher concentrations can kill the cilia or inhibit macrophage function. As a result, the pollutants can reduce the body’s defenses and increase susceptibility to disease.

The Association of Air Pollution with Human Health Problems

Three types of studies are used to determine the health effects of air pollutants. While these studies have provided invaluable information, they each have their strengths and weaknesses.

1. Animal toxicology studies - Dose-response curves (i.e. what effects are seen at different concentrations of a toxic substance) are determined using experimental animals to ascertain the pathological effects of varying doses of a single air pollutant. Thus, one can determine precisely how a given pollutant at a certain dose effects the structure and function of the respiratory system. These studies are not acceptable in humans when one is looking for severe damage. The problem with animal studies, however, is that we must extrapolate the quantitative results to humans and animals may differ in their sensitivity to the pollutant as compared to humans.

2. Human studies may be conducted when one is determining acute, short-term reversible effects of the criteria air pollutants since these are the pollutants to which people are exposed daily. While these studies are obviously advantageous in that they do not involve extrapolation from animal studies, they are limited in the following ways: a) there are restrictions on the endpoints (i.e. pathological effects) that can be studied as potentially irreversible effects and carcinogenicity are always of concern, b) variety of toxicants which can be studied especially if there is lack of knowledge about the substance, c) inability to address chronic exposures, etc.

3. Epidemiologic studies - These studies show the association between exposure to a pollutant and the health effects in a population of individuals. These data are advantageous in that they involve large numbers of individuals exposed under "real life" conditions but it is difficult to control other variables such as differences among individuals in regard to health status and habits, socioeconomic level, etc. Thus, only associations can be drawn between the exposure and the effect; i.e. a direct causal relationship cannot be determined.

Air Pollution & Respiratory Disease

Four of the criteria air pollutants--particulate matter, sulfur dioxide, nitrogen dioxide and ozone--have been implicated as a causal or aggravating agent in the a variety of diseases of the respiratory system including chronic bronchitis, pulmonary emphysema, and asthma. Carbon monoxide and lead affect other organ systems and will be discussed with these systems. The evidence of a causal role for ambient air pollution in lung cancer is inconsistent, although many scientists do support this association.

1. Chronic Bronchitis - Characterized by inflammation of the membrane lining the bronchial airways. When this inflammation persists for three months or longer, it is known as chronic bronchitis which is manifested by a persistent cough and excessive mucous and sputum production. Because chronic bronchitis results in the closing of the bronchi, swelling of inflamed membranes, and increased mucous production, individuals have difficulty breathing. Destruction of cilia can also occur. Epidemiological and toxicological evidence suggest that exposure to a combination of particulate matter and sulfur dioxide may lead to the initiation of chronic bronchitis as a result of long-term community air pollution exposure.

2. Emphysema - Characterized by a destruction or degeneration of the walls of the alveolar sacs which results in a reduction of the total surface area of pulmonary tissue. The lungs lose their elasticity and the airways narrow. As a result, patients with emphysema have shortness of breath and difficulty in breathing, especially exhaling, due to the compression and collapse of some of the small airways and overall decrease in lung elasticity.
Animal studies suggest that chronic exposure to nitrous oxides can predispose to emphysema.

3. Asthma - Asthma is characterized by constriction of the respiratory muscles and episodal construction of the respiratory airways resulting in difficulty in breathing, especially expiration. Characteristic symptoms include wheezing especially after expiration, chest tightness, cough and shortness of breath.
Asthmatic attacks may result from a variety of nonspecific irritants which are thought to include sulfur dioxide and particulate matter. We have seen a drastic increase in the incidence of asthma, but do not know why.

Formation of Ozone

Ozone and numerous reactive organic compounds are formed as a result of chemical reactions between nitrogen oxides and volatile organic compounds. Because sunlight is necessary to provide the energy to propel these reactions, ozone and the other compounds are collectively known as photochemical oxidants, although the more common name for these products is smog.

During incomplete combustion of the internal combustion engine, hydrocarbons (also known as volatile organic compounds or fragments of hydrocarbon fuels from incomplete combustion) as well as nitrogen oxides (there are a variety of these) are formed. (See EPA sheet on Automobile Emissions.) As shown in the accompanying figure, it is the volatile organic compounds which are the real culprit in this process.

Without the pressure of VOCs, the nitrogen dioxide would split to form nitric oxide and atomic oxygen in the presence of sunlight. Although atomic acid combines with oxygen gas in the atmosphere to form ozone, this ozone immediately reacts with nitric oxide to form nitrogen dioxide and oxygen gas. There is no appreciable accumulation of ozone and thus, summer concentrations of ozone in unpolluted air would remain far below those considered harmful.

In the presence of volatile organic compounds, however, the nitric oxide favors reacting with the volatile organic compounds and leads to the creation of peroxyacetyl nitrates or PANs, which are highly reactive and damaging to plants and animals. VOCs also combine with atomic oxygen to form aldehydes and ketomes which are also toxic. Most importantly, because the nitric oxide is tied up with the VOCs, it cannot react with the ozone that is being formed and, as a result, high accumulations of ozone result.

Because hydrocarbons (volatile organic compounds) are the biggest problem in this situation, these are one of the pollutants tested for during automobile emission tests. This is also the reason that on bad ozone days, you should not use lawnmowers or weed wackers because they are actually bigger sources of hydrocarbon emissions than are automobiles. It should also be noted that the geography of an area plays a role in the buildup of ozone.

What Does Ozone Do to the Respiratory Tract?

Ozone destroys the lipids and the proteins in the membranes of pulmonary macrophages, which again are one of the lines of defense in the lungs. Because macrophages eat ozone particles and destroy their toxicity, if you destroy these macrophages, you are destroying the body’s ability to defend itself. Studies with animals have shown that when this occurs, the animals die with subsequent exposure to bacteria. Presumptive evidence looks like a similar mechanism may occur in Mexico City with human beings. In this city, air pollution is severe with ozone as well as lead from unleaded gasoline. Furthermore, because of inadequate treatment of human wastes, there are lots of bacteria in the air. This creates the scenario for a high incidence of bacterial infections, and indeed, this is the case.

Unfortunately, the story with ozone does not stop here. Once macrophages in the lung become damaged, they "call in " other cells, particularly polymorphonucler neutrophils to help them. Remember that these cells make toxic enzymes to destroy pathogens. When these neutrophils enter the lungs, they release these toxic enzymes that result in pulmonary inflammation.

REFERENCES

Andesirk, T. and Andesirk, G.: Biology: Life on Earth, ed. 5, Upper Saddle River, New Jersey, 1999, Prentice-Hall, Inc.

.F Cox, S.I.: Human Physiology, ed. 5, Dubuque, Iowa, 1996, William C. Brown Publishers.

Godish, T.: Air Quality, ed. 3, Boca Raton, Florida, 1997, Lewis Publishers/CRC Press.

John Hopkins University, Environmental Toxicology Course (Summer Institute, 1998).

Klaassen, C.D., editor: Casarett and Doull’s Toxicology: The Basic Science of Poisons, ed. 5, New York, New York, 1996, McGraw-Hill.

Mader, S.S.: Biology, ed. 6, Boston, Massachusetts, 1998, WCB/McGraw-Hill.

Moeller, D.W.: Environmental Health, rev. ed., Cambridge, Massachusetts, 1997, Harvard University Press.

Nadakavukaren, A.: Our Global Environment: A Health Perspective, ed. 4, Prospect Heights, Illinois, 1995, Waveland Press, Inc.

Nebel, B.J. and Wright, R.T.: Environmental Science, ed. 6, Upper Saddle River, New Jersey, 1998, Prentice-Hall, Inc.

Sherwood, L.: Fundamentals of Physiology: A Human Perspective, St. Paul, Minnesota, 1991, West Publishing Company.

Vander, A.J., Sherman, J.H., and Luciano, D.S.: Human Physiology: The Mechanisms of Body Function, ed. 6, New York, 1994, McGraw-Hill, Inc.

Study Questions

1. Name the parts of the respiratory system. Which comprise the conducting system and which comprise the gas exchange portion? What is the role of each in regard to the respiratory tract?

2. Discuss the principles that govern gas exchange in the lungs.

3. Describe the mechanical process of breathing.

4. List the defense systems of the respiratory tract. What do air pollutants to do these defense mechanisms?

5. What types of studies are done to determine the toxicity of air pollutants? What are the strengths and weaknesses of each of these?

6. Describe the following respiratory infections and tell what pollutants each has been associated with: emphysema, bronchitis, asthma.

7. In regard to ozone, discuss the following: a) formation and b) health effects.

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