When you're short of breath, it's hard or uncomfortable for you to take in the oxygen your body needs. You may feel as if you're not getting enough air. Sometimes you can have mild breathing problems because of a stuffy nose or intense exercise. But shortness of breath can also be a sign of a serious disease.

Many conditions can make you feel short of breath:

• Lung conditions such as asthma, emphysema, or pneumonia
• Problems with your trachea or bronchi, which are part of your airway system
• Heart disease can make you feel breathless if your heart cannot pump enough blood to supply oxygen to your body
• Anxiety and panic attacks
• Allergies

If you often have trouble breathing, it is important to find out the cause.

What is dyspnea?

Dyspnea (pronounced disp–NEE–uh) is a medical term for difficult or labored breathing. Having dyspnea can be hard to live with. You may get short of breath during daily activities and become anxious when your breathing changes. Medications may help, and, to get the most benefit, you should take them exactly as instructed by your healthcare team.

Experts such as respiratory therapists, physical therapists, respiratory nurses, and pulmonary specialists will work with you to develop ways to help you breathe and manage dyspnea. These methods include pursed-lip breathing, positioning, paced breathing, and desensitization. Pulmonary exercises for dyspnea are specific for each person.

Pursed-lip breathing

This method may seem awkward at first, but it eases labored breathing.

• Breathe in through your mouth or nose.
• Purse your lips together (as if you were whistling). Then, breathe out.
• Try to breathe out until all of the air in your lungs is gone. One way to do this is to take twice as long to breathe out as you do to breathe in. For example, count “one…two” as you breathe in. Purse your lips, then count “one…two… three…four” as you breathe out.

Positioning

When your muscles are relaxed, breathing is easier. Positioning helps when you get short of breath while doing activities, such as climbing stairs.

• Rest against the wall and lean forward with your hands on your thighs. This position relaxes your chest and shoulders, freeing them to help you breathe. Use pursed-lip breathing.
• If you can, sit down with your arms resting on your legs. Continue to do pursed-lip breathing.

If you find it hard to relax your muscles, then ask your nurse to show you other ways to do this. Other body positions may also work for you. Try them until you find the best one.

Paced Breathing

Paced breathing prevents or decreases shortness of breath when you walk or lift light objects. When walking, pace yourself, and move slowly.

For walking:

• Stand still, and breathe in.
• Walk a few steps, and breathe out.
• Rest, and begin again.

For lifting:

• Before lifting take a deep breath. When carrying something, hold it close to your body while walking and breathing. This saves energy.

Desensitization

Part of living with dyspnea is getting accustomed to it. Desensitization means that you are not so afraid when you are short of breath. These guidelines will help you get “desensitized.”

• Do pursed-lip breathing, positioning, and paced breathing. Breathing with these methods will build your confidence. When shortness of breath occurs, you will be able to deal with it.
• Ask friends and family to understand. Let people around you know when you are short of breath. You do not need to feel embarrassed when you cannot join others in some activities. By doing the methods explained here, you will still be able to do what you always did; you may just need to take a little longer or do them differently.

Many conditions can cause dyspnea.

Dyspnea is the feeling of difficult or uncomfortable breathing or of not getting enough air. It also may be called shortness of breath, breathlessness, or air hunger. In cancer patients, causes of dyspnea include the following:

• Effects related to the tumor:
  • The tumor blocks the airways in the chest and lung or the vein that carries bloodthrough the chest to the heart.
  • The tumor causes extra fluid to build up in the space between the thin layer of tissue covering the lung and the thin layer of tissue covering the chest wall (pleural effusion), between the sac that covers the heart and the heart (pericardial effusion), or in the abdominal cavity (ascites).
  • Carcinomatous lymphangitis (inflammation of the lymph vessels).
  • Chest infections. Some cancer treatments may increase the risk of an infection, such as pneumonia.
  • Blood clots or tumor cells break loose and block a blood vessel in the lungs.
  • Paralysis of part of the diaphragm (a muscle used for breathing).
  • Breathing muscles get weaker.
• Effects related to treatment:
  • Damage to the lung caused by radiation therapy or chemotherapy. A very small number of women who receive radiation therapy for breast cancer develop postradiation bronchiolitis obliterans, a condition in which the bronchioles (tiny branches of air tubes in the lungs) become inflamed and blocked.
  • Weakened heart muscle caused by chemotherapy.
• Conditions that are not related to cancer:
  • Chronic obstructive pulmonary disease (COPD), such as chronic bronchitis or emphysema.
  • Bronchospasm. The muscles in the airways contract and cause spasms.
  • A weak diaphragm.
  • Congestive heart failure.
  • Anemia.
• Conditions with no known physical cause, such as anxiety.

A diagnosis of the cause of dyspnea helps to plan treatment.

Diagnostic tests and procedures include the following:

• Physical exam and history: An exam of the body to check general signs of health, including checking for signs or symptoms of dyspnea, such as breathing fast or using the neck or chest muscles to breathe. A history of your health habits and past illnesses and treatments will also be taken. Your doctor will also ask about when the dyspnea occurs, what it feels like, other signs or symptoms that happen at the same time as the dyspnea, and anything that makes it better or worse.
• Functional assessment: An exam to check for how the dyspnea affects your ability to perform activities of daily living such as eating, bathing, or climbing stairs. This exam may include a 6-minute walk test (6MWT) to measure how far you can walk on a flat, hard surface in 6 minutes.
• Chest x-ray: An x-ray of the organs and bones inside the chest. An x-ray is a type of energy beam that can go through the body and onto film, making a picture of areas inside the body.

• CT scan (CAT scan): A procedure that makes a series of detailed pictures of areas inside the body, taken from different angles. The pictures are made by a computer linked to an x-ray machine. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography.
• Complete blood count: A procedure in which a sample of blood is taken and checked for the following:
  • The number of red blood cells, white blood cells, and platelets.
  • The amount of hemoglobin (the protein that carries oxygen) in the red blood cells.
  • The portion of the blood sample made of red blood cells.
• Oxygen saturation test: A procedure to check for the amount of oxygen being carried by the red blood cells. A lower than normal amount of oxygen may be a sign of lung disease or other health problems. One method uses a device clipped to the finger. The device senses the amount of oxygen in the blood flowing through the small blood vessels in the finger. Another method uses a sample of blood taken from an artery, usually in the wrist, that is tested for the amount of oxygen.
• Maximum inspiratory pressure (MIP) test: The MIP is the highest pressure that can be reached in the lungs when you take a deep breath. When you breathe through a device called a manometer, the device measures the pressure. The information is sent to a computer. The pressure level shows how strong the breathing muscles are.

It may be possible to treat the cause of dyspnea.

Treatment may include the following:

• Radiation therapy: Radiation therapy is a cancer treatment that uses high-energy x-rays or other types of radiation to kill cancer cells or keep them from growing. External radiation therapy uses a machine outside the body to send radiation toward the cancer.
• Chemotherapy: Chemotherapy is a cancer treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. When chemotherapy is taken by mouth or injected into a vein or muscle, the drugs enter the bloodstream and can reach cancer cells throughout the body (systemic chemotherapy). When chemotherapy is placed directly into the cerebrospinal fluid, an organ, or a body cavity such as the abdomen, the drugs mainly affect cancer cells in those areas (regional chemotherapy). The way the chemotherapy is given depends on the type and stage of the cancer being treated.
• Laser therapy for tumors inside large airways: Use of a laser beam (a narrow beam of intense light) as a knife to remove the tumor.
• Cauterization of tumors inside large airways: Use of a hot instrument, an electric current, or a caustic substance to destroy the tumor.
• Procedures to remove fluid that has built up around the lungs (malignant pleural effusion), around the heart (malignant pericardial effusion ), or in the abdominal cavity (ascites). (See the sections on controlling the signs and symptoms of malignant pleural effusion and malignant pericardial effusion for more information.)
• Stent placement: Surgery to place a stent (thin tube) in an airway to keep it open. This may be done if a large airway is blocked by a tumor that is pressing on it from the outside.
• Medicine:
  • Steroid drugs for inflamed or swollen lymph vessels in the lungs.
  • Antibiotics for chest infections. These may be used with chest physical therapy.
  • Anticoagulants for blood clots that are blocking blood vessels in the lungs.
  • Bronchodilators that are inhaled to open up the bronchioles (small airways) in the lungs.
  • Diuretics and other drugs for heart failure.
• Blood transfusions for anemia.

Treatment of dyspnea depends on the cause of it.

The treatment of dyspnea depends on its cause, as follows:

Treatment may be to control the signs and symptoms of dyspnea.

Treatment to control the signs and symptoms of dyspnea may include the following:

• Oxygen therapy: Patients who cannot get enough oxygen from the air may be given extra oxygen to inhale from a tank. Devices that increase the amount of oxygen already in the air may also be prescribed.
• Medicines: Opioids, such as morphine, may lessen physical and mental distress and exhaustion and the feeling that the patient cannot take in enough air. Other drugs may be used to treat dyspnea that is related to panic disorder or severe anxiety.
• Supportive care:
  • Breathing methods, such as breathing with the lips pursed (almost closed).
  • Using a fan to blow cold air across the cheek.
  • Meditation.
  • Relaxation training.
  • Biofeedback.
  • Talk therapy to relieve anxiety.

Hyperventilation: increased ventilation rate that leads to abnormally low blood carbon dioxide levels and high (alkaline) blood pH

Hyperpnea is an increased depth and rate of ventilation to meet an increase in oxygen demand as might be seen in exercise or disease, particularly diseases that target the respiratory or digestive tracts. This does not significantly alter blood oxygen or carbon dioxide levels, but merely increases the depth and rate of ventilation to meet the demand of the cells. In contrast, hyperventilation is an increased ventilation rate that is independent of the cellular oxygen needs and leads to abnormally low blood carbon dioxide levels and high (alkaline) blood pH.

Wheezing is commonly experienced by people who have asthma; although, it can be heard in people with foreign bodies, congestive heart failure, a malignancy of the airway, or any lesion that causes narrowing of the airways. The presence of wheezing during expiration indicates that the individual’s peak expiratory flow rate is less than fifty percent compared to normal. The quality and duration of wheezing also depend on where in the airways the obstruction is located. In asthma, the wheezing is due to narrowing of the lower airways whereas with malignancies the obstruction is usually in the upper, more proximal airways. In rare cases, wheezing may be heard both during inspiration and expiration. In severe asthma, in fact, no wheeze may be heard as the air flow will be so severely reduced and chest auscultation will be silent. Since any process that reduces airway caliber generates wheeze, below are some of the many of the conditions that can cause wheeze:

• Respiratory infections (croup, laryngitis)
• Obstructive airway diseases (asthma,
• chronic obstructive pulmonary disease [COPD], anaphylaxis, bronchiolitis)
• Pulmonary peribronchial edema (congestive heart failure)
• Vocal cord dysfunction (paradoxical vocal fold motion [PVFM], vocal cord paralysis)
• Post nasal drip
• Airway compression: Intrinsic or extrinsic (squamous cell carcinomas, goiter)
• Hyperdynamic airway collapse (tracheobronchomalacia)
• Carcinoid tumors
• Foreign body inhalation
• Forced exhalation by normal individuals

A collapsed lung happens when air enters the pleural space, the area between the lung and the chest wall. If it is a total collapse, it is called pneumothorax. If only part of the lung is affected, it is called atelectasis.

Causes of a collapsed lung include

• Lung diseases such as pneumonia or lung cancer
• Being on a breathing machine
• Surgery on the chest or abdomen
• A blocked airway

If only a small area of the lung is affected, you may not have symptoms. If a large area is affected, you may feel short of breath and have a rapid heart rate.

A chest x-ray can tell if you have it. Treatment depends on the underlying cause.

Respiratory syncytial virus (RSV) is a contagious virus that affects the lungs and breathing passages. Most children get RSV infection by age 2, but you can get infected at any age and more than once in your life. The symptoms are usually similar to the common cold. Most people recover in a week or two, but others at high risk may get very sick and develop pneumonia or bronchiolitis (inflammation of the small airways in the lungs). There is no vaccine, but scientists are working to develop one. Until then, there are ways you can help prevent RSV infection.

Key Facts

• RSV usually causes mild, cold-like symptoms such as runny nose, decrease in appetite, coughing, sneezing, fever, and wheezing.
• Infants and older adults may develop severe infections from RSV, such as pneumonia or bronchiolitis.
• Most kids get an RSV infection by age 2. However, you can get an RSV infection at any age and more than once in your life.
• RSV spreads when an infected person coughs or sneezes, or shares cups and eating utensils with others.
• You can help protect yourself and others from RSV infections by washing your hands often with soap and water for at least 20 seconds.

RSV Can Be Serious

For most people, RSV infections are mild and clear on their own. But some people develop severe infections, such as pneumonia and bronchiolitis. People at high risk include very young infants, premature babies, young children with chronic lung or heart disease, older adults, and people with weakened immune systems.

Wash Your Hands Often

Wash your hands often with soap and water for 20 seconds, and help young children do the same. Proper hand hygiene can help protect you from getting RSV infection as well as prevent the spread of infection to others when you are sick.

Cover Your Cough and Sneeze

RSV can spread when an infected person coughs or sneezes. To help prevent germs from spreading, cover your coughs and sneezes with a tissue or your upper shirt sleeve, not your bare hands. Throw the tissue in the trash and wash your hands.

Avoid Sharing When Sick

You can get RSV infection if you share cups or eating utensils with others. You can also get infected if you touch surfaces, such as toys or doorknobs, that have the virus on them, then touch your eyes, nose or mouth.

Prevention Tips

• Wash your hands often with soap and water for at least 20 seconds, and help young children do the same.
• Cover your coughs and sneezes with a tissue or your upper shirt sleeve, not your bare hands. Throw the tissue in the trash and wash your hands.
• Avoid touching your eyes, nose, and mouth with unwashed hands.
• Avoid close contact, such as kissing, or sharing cups or eating utensils, with sick people.
• Clean and disinfect frequently touched surfaces, such as toys and doorknobs.

Inhalation injuries are acute injuries to your respiratory system and lungs. They can happen if you breathe in toxic substances, such as smoke (from fires), chemicals, particle pollution, and gases. Inhalation injuries can also be caused by extreme heat; these are a type of thermal injuries. Over half of deaths from fires are due to inhalation injuries.

Symptoms of inhalation injuries can depend on what you breathed in. But they often include

• Coughing and phlegm
• A scratchy throat
• Irritated sinuses
• Shortness of breath
• Chest pain or tightness
• Headaches
• Stinging eyes
• A runny nose

If you have a chronic heart or lung problem, an inhalation injury can make it worse.

To make a diagnosis, your health care provider may use a scope to look at your airways and check for damage. Other possible tests include imaging tests of the lungs, blood tests, and lung function tests.

If you have an inhalation injury, your health care provider will make sure that your airway is not blocked. Treatment is with oxygen therapy, and in some cases, medicines. Some patients need to use a ventilator to breathe. Most people get better, but some people have permanent lung or breathing problems. Smokers and people who had a severe injury are at a greater risk of having permanent problems.

You can take steps to try to prevent inhalation injuries:

• At home, practice fire safety, which includes preventing fires and having a plan in case there is a fire
• If there is smoke from a wildfire nearby or lots of particulate pollution in the air, try to limit your time outdoors. Keep your indoor air as clean as possible, by keeping windows closed and using an air filter. If you have asthma, another lung disease, or heart disease, follow your health care provider's advice about your medicines and respiratory management plan.
• If you are working with chemicals or gases, handle them safely and use protective equipment

Mammalian lungs are located in the thoracic cavity where they are surrounded and protected by the rib cage, intercostal muscles, and bound by the chest wall. The bottom of the lungs is contained by the diaphragm, a skeletal muscle that facilitates breathing. Breathing requires the coordination of the lungs, the chest wall, and most importantly, the diaphragm.

Types of Breathing

Amphibians have evolved multiple ways of breathing. Young amphibians, like tadpoles, use gills to breathe, and they don’t leave the water. Some amphibians retain gills for life. As the tadpole grows, the gills disappear and lungs grow. These lungs are primitive and not as evolved as mammalian lungs. Adult amphibians are lacking or have a reduced diaphragm, so breathing via lungs is forced. The other means of breathing for amphibians is diffusion across the skin. To aid this diffusion, amphibian skin must remain moist.

Birds face a unique challenge with respect to breathing: They fly. Flying consumes a great amount of energy; therefore, birds require a lot of oxygen to aid their metabolic processes. Birds have evolved a respiratory system that supplies them with the oxygen needed to enable flying. Similar to mammals, birds have lungs, which are organs specialized for gas exchange. Oxygenated air, taken in during inhalation, diffuses across the surface of the lungs into the bloodstream, and carbon dioxide diffuses from the blood into the lungs and expelled during exhalation. The details of breathing between birds and mammals differ substantially.

In addition to lungs, birds have air sacs inside their body. Air flows in one direction from the posterior air sacs to the lungs and out of the anterior air sacs. The flow of air is in the opposite direction from blood flow, and gas exchange takes place much more efficiently. This type of breathing enables birds to obtain the requisite oxygen, even at higher altitudes where the oxygen concentration is low. This directionality of airflow requires two cycles of air intake and exhalation to completely get the air out of the lungs.

Avian Respiration

Birds have evolved a respiratory system that enables them to fly. Flying is a high-energy process and requires a lot of oxygen. Furthermore, many birds fly in high altitudes where the concentration of oxygen is low. How did birds evolve a respiratory system that is so unique?

Decades of research by paleontologists have shown that birds evolved from therapods, meat-eating dinosaurs (Figure 39.14). In fact, fossil evidence shows that meat-eating dinosaurs that lived more than 100 million years ago had a similar flow-through respiratory system with lungs and air sacs. Archaeopteryx and Xiaotingia, for example, were flying dinosaurs and are believed to be early precursors of birds.

Figure 39.14 Dinosaurs, from which birds descended, have similar hollow bones and are believed to have had a similar respiratory system. (credit b: modification of work by Zina Deretsky, National Science Foundation)

Most of us consider that dinosaurs are extinct. However, modern birds are descendants of avian dinosaurs. The respiratory system of modern birds has been evolving for hundreds of millions of years.

All mammals have lungs that are the main organs for breathing. Lung capacity has evolved to support the animal’s activities. During inhalation, the lungs expand with air, and oxygen diffuses across the lung’s surface and enters the bloodstream. During exhalation, the lungs expel air and lung volume decreases. In the next few sections, the process of human breathing will be explained.

The Mechanics of Human Breathing

Boyle’s Law is the gas law that states that in a closed space, pressure and volume are inversely related. As volume decreases, pressure increases and vice versa (Figure 39.15). The relationship between gas pressure and volume helps to explain the mechanics of breathing.

Figure 39.15 This graph shows data from Boyle’s original 1662 experiment, which shows that pressure and volume are inversely related. No units are given as Boyle used arbitrary units in his experiments.

There is always a slightly negative pressure within the thoracic cavity, which aids in keeping the airways of the lungs open. During inhalation, volume increases as a result of contraction of the diaphragm, and pressure decreases (according to Boyle’s Law). This decrease of pressure in the thoracic cavity relative to the environment makes the cavity less than the atmosphere (Figure 39.16a). Because of this drop in pressure, air rushes into the respiratory passages. To increase the volume of the lungs, the chest wall expands. This results from the contraction of the intercostal muscles, the muscles that are connected to the rib cage. Lung volume expands because the diaphragm contracts and the intercostal muscles contract, thus expanding the thoracic cavity. This increase in the volume of the thoracic cavity lowers pressure compared to the atmosphere, so air rushes into the lungs, thus increasing its volume. The resulting increase in volume is largely attributed to an increase in alveolar space, because the bronchioles and bronchi are stiff structures that do not change in size.

Figure 39.16 The lungs, chest wall, and diaphragm are all involved in respiration, both (a) inhalation and (b) expiration. (credit: modification of work by Mariana Ruiz Villareal)

The chest wall expands out and away from the lungs. The lungs are elastic; therefore, when air fills the lungs, the elastic recoil within the tissues of the lung exerts pressure back toward the interior of the lungs. These outward and inward forces compete to inflate and deflate the lung with every breath. Upon exhalation, the lungs recoil to force the air out of the lungs, and the intercostal muscles relax, returning the chest wall back to its original position (Figure 39.16b). The diaphragm also relaxes and moves higher into the thoracic cavity. This increases the pressure within the thoracic cavity relative to the environment, and air rushes out of the lungs. The movement of air out of the lungs is a passive event. No muscles are contracting to expel the air.

Each lung is surrounded by an invaginated sac. The layer of tissue that covers the lung and dips into spaces is called the visceral pleura. A second layer of parietal pleura lines the interior of the thorax (Figure 39.17). The space between these layers, the intrapleural space, contains a small amount of fluid that protects the tissue and reduces the friction generated from rubbing the tissue layers together as the lungs contract and relax. Pleurisy results when these layers of tissue become inflamed; it is painful because the inflammation increases the pressure within the thoracic cavity and reduces the volume of the lung.

Figure 39.17 A tissue layer called pleura surrounds the lung and interior of the thoracic cavity. (credit: modification of work by NCI)

The Work of Breathing

The number of breaths per minute is the respiratory rate. On average, under non-exertion conditions, the human respiratory rate is 12–15 breaths/minute. The respiratory rate contributes to the alveolar ventilation, or how much air moves into and out of the alveoli. Alveolar ventilation prevents carbon dioxide buildup in the alveoli. There are two ways to keep the alveolar ventilation constant: increase the respiratory rate while decreasing the tidal volume of air per breath (shallow breathing), or decrease the respiratory rate while increasing the tidal volume per breath. In either case, the ventilation remains the same, but the work done and type of work needed are quite different. Both tidal volume and respiratory rate are closely regulated when oxygen demand increases.

There are two types of work conducted during respiration, flow-resistive and elastic work. Flow-resistive refers to the work of the alveoli and tissues in the lung, whereas elastic work refers to the work of the intercostal muscles, chest wall, and diaphragm. Increasing the respiration rate increases the flow-resistive work of the airways and decreases the elastic work of the muscles. Decreasing the respiratory rate reverses the type of work required.

Surfactant

The air-tissue/water interface of the alveoli has a high surface tension. This surface tension is similar to the surface tension of water at the liquid-air interface of a water droplet that results in the bonding of the water molecules together. Surfactant is a complex mixture of phospholipids and lipoproteins that works to reduce the surface tension that exists between the alveoli tissue and the air found within the alveoli. By lowering the surface tension of the alveolar fluid, it reduces the tendency of alveoli to collapse.

Surfactant works like a detergent to reduce the surface tension and allows for easier inflation of the airways. When a balloon is first inflated, it takes a large amount of effort to stretch the plastic and start to inflate the balloon. If a little bit of detergent was applied to the interior of the balloon, then the amount of effort or work needed to begin to inflate the balloon would decrease, and it would become much easier to start blowing up the balloon. This same principle applies to the airways. A small amount of surfactant to the airway tissues reduces the effort or work needed to inflate those airways. Babies born prematurely sometimes do not produce enough surfactant. As a result, they suffer from respiratory distress syndrome, because it requires more effort to inflate their lungs. Surfactant is also important for preventing collapse of small alveoli relative to large alveoli.

Lung Resistance and Compliance

Pulmonary diseases reduce the rate of gas exchange into and out of the lungs. Two main causes of decreased gas exchange are compliance (how elastic the lung is) and resistance (how much obstruction exists in the airways). A change in either can dramatically alter breathing and the ability to take in oxygen and release carbon dioxide.

Examples of restrictive diseases are respiratory distress syndrome and pulmonary fibrosis. In both diseases, the airways are less compliant and they are stiff or fibrotic. There is a decrease in compliance because the lung tissue cannot bend and move. In these types of restrictive diseases, the intrapleural pressure is more positive and the airways collapse upon exhalation, which traps air in the lungs. Forced or functional vital capacity (FVC), which is the amount of air that can be forcibly exhaled after taking the deepest breath possible, is much lower than in normal patients, and the time it takes to exhale most of the air is greatly prolonged (Figure 39.18). A patient suffering from these diseases cannot exhale the normal amount of air.

Obstructive diseases and conditions include emphysema, asthma, and pulmonary edema. In emphysema, which mostly arises from smoking tobacco, the walls of the alveoli are destroyed, decreasing the surface area for gas exchange. The overall compliance of the lungs is increased, because as the alveolar walls are damaged, lung elastic recoil decreases due to a loss of elastic fibers, and more air is trapped in the lungs at the end of exhalation. Asthma is a disease in which inflammation is triggered by environmental factors. Inflammation obstructs the airways. The obstruction may be due to edema (fluid accumulation), smooth muscle spasms in the walls of the bronchioles, increased mucus secretion, damage to the epithelia of the airways, or a combination of these events. Those with asthma or edema experience increased occlusion from increased inflammation of the airways. This tends to block the airways, preventing the proper movement of gases (Figure 39.18). Those with obstructive diseases have large volumes of air trapped after exhalation and breathe at a very high lung volume to compensate for the lack of airway recruitment.

Figure 39.18 The ratio of FEV1 (the amount of air that can be forcibly exhaled in one second after taking a deep breath) to FVC (the total amount of air that can be forcibly exhaled) can be used to diagnose whether a person has restrictive or obstructive lung disease. In restrictive lung disease, FVC is reduced but airways are not obstructed, so the person is able to expel air reasonably fast. In obstructive lung disease, airway obstruction results in slow exhalation as well as reduced FVC. Thus, the FEV1/FVC ratio is lower in persons with obstructive lung disease (less than 69 percent) than in persons with restrictive disease (88 to 90 percent).

Dead Space: V/Q Mismatch

Pulmonary circulation pressure is very low compared to that of the systemic circulation. It is also independent of cardiac output. This is because of a phenomenon called recruitment, which is the process of opening airways that normally remain closed when cardiac output increases. As cardiac output increases, the number of capillaries and arteries that are perfused (filled with blood) increases. These capillaries and arteries are not always in use but are ready if needed. At times, however, there is a mismatch between the amount of air (ventilation, V) and the amount of blood (perfusion, Q) in the lungs. This is referred to as ventilation/perfusion (V/Q) mismatch.

There are two types of V/Q mismatch. Both produce dead space, regions of broken down or blocked lung tissue. Dead spaces can severely impact breathing, because they reduce the surface area available for gas diffusion. As a result, the amount of oxygen in the blood decreases, whereas the carbon dioxide level increases. Dead space is created when no ventilation and/or perfusion takes place. Anatomical dead space or anatomical shunt, arises from an anatomical failure, while physiological dead space or physiological shunt, arises from a functional impairment of the lung or arteries.

An example of an anatomical shunt is the effect of gravity on the lungs. The lung is particularly susceptible to changes in the magnitude and direction of gravitational forces. When someone is standing or sitting upright, the pleural pressure gradient leads to increased ventilation further down in the lung. As a result, the intrapleural pressure is more negative at the base of the lung than at the top, and more air fills the bottom of the lung than the top. Likewise, it takes less energy to pump blood to the bottom of the lung than to the top when in a prone position. Perfusion of the lung is not uniform while standing or sitting. This is a result of hydrostatic forces combined with the effect of airway pressure. An anatomical shunt develops because the ventilation of the airways does not match the perfusion of the arteries surrounding those airways. As a result, the rate of gas exchange is reduced. Note that this does not occur when lying down, because in this position, gravity does not preferentially pull the bottom of the lung down.

A physiological shunt can develop if there is infection or edema in the lung that obstructs an area. This will decrease ventilation but not affect perfusion; therefore, the V/Q ratio changes and gas exchange is affected.

The lung can compensate for these mismatches in ventilation and perfusion. If ventilation is greater than perfusion, the arterioles dilate and the bronchioles constrict. This increases perfusion and reduces ventilation. Likewise, if ventilation is less than perfusion, the arterioles constrict and the bronchioles dilate to correct the imbalance.

What Happens When You Breathe?

Breathing In (Inhalation)

When you breathe in, or inhale, your diaphragm contracts (tightens) and moves downward. This increases the space in your chest cavity, into which your lungs expand. The intercostal muscles between your ribs also help enlarge the chest cavity. They contract to pull your rib cage both upward and outward when you inhale.

As your lungs expand, air is sucked in through your nose or mouth. The air travels down your windpipe and into your lungs. After passing through your bronchial tubes, the air finally reaches and enters the alveoli (air sacs).

Through the very thin walls of the alveoli, oxygen from the air passes to the surrounding capillaries (blood vessels). A red blood cell protein called hemoglobin (HEE-muh-glow-bin) helps move oxygen from the air sacs to the blood.

At the same time, carbon dioxide moves from the capillaries into the air sacs. The gas has traveled in the bloodstream from the right side of the heart through the pulmonary artery.

Oxygen-rich blood from the lungs is carried through a network of capillaries to the pulmonary vein. This vein delivers the oxygen-rich blood to the left side of the heart. The left side of the heart pumps the blood to the rest of the body. There, the oxygen in the blood moves from blood vessels into surrounding tissues.

Breathing Out (Exhalation)

When you breathe out, or exhale, your diaphragm relaxes and moves upward into the chest cavity. The intercostal muscles between the ribs also relax to reduce the space in the chest cavity.

As the space in the chest cavity gets smaller, air rich in carbon dioxide is forced out of your lungs and windpipe, and then out of your nose or mouth.

Breathing out requires no effort from your body unless you have a lung disease or are doing physical activity. When you're physically active, your abdominal muscles contract and push your diaphragm against your lungs even more than usual. This rapidly pushes air out of your lungs.

The animation below shows how the lungs work. Click the "start" button to play the animation. Written and spoken explanations are provided with each frame. Use the buttons in the lower right corner to pause, restart, or replay the animation, or use the scroll bar below the buttons to move through the frames.

National Cancer Institute / NIH

The major organs of the respiratory system function primarily to provide oxygen to body tissues for cellular respiration, remove the waste product carbon dioxide, and help to maintain acid-base balance. Portions of the respiratory system are also used for non-vital functions, such as sensing odors, speech production, and for straining, such as during childbirth or coughing (Figure).

Functionally, the respiratory system can be divided into a conducting zone and a respiratory zone. The conducting zone of the respiratory system includes the organs and structures not directly involved in gas exchange. The gas exchange occurs in the respiratory zone.

Conducting Zone

The major functions of the conducting zone are to provide a route for incoming and outgoing air, remove debris and pathogens from the incoming air, and warm and humidify the incoming air. Several structures within the conducting zone perform other functions as well. The epithelium of the nasal passages, for example, is essential to sensing odors, and the bronchial epithelium that lines the lungs can metabolize some airborne carcinogens.

The Nose and its Adjacent Structures

The major entrance and exit for the respiratory system is through the nose. When discussing the nose, it is helpful to divide it into two major sections: the external nose, and the nasal cavity or internal nose.

The external nose consists of the surface and skeletal structures that result in the outward appearance of the nose and contribute to its numerous functions (Figure). The root is the region of the nose located between the eyebrows. The bridge is the part of the nose that connects the root to the rest of the nose. The dorsum nasi is the length of the nose. The apex is the tip of the nose. On either side of the apex, the nostrils are formed by the alae (singular = ala). An ala is a cartilaginous structure that forms the lateral side of each naris (plural = nares), or nostril opening. The philtrum is the concave surface that connects the apex of the nose to the upper lip.

Underneath the thin skin of the nose are its skeletal features (see Figure, lower illustration). While the root and bridge of the nose consist of bone, the protruding portion of the nose is composed of cartilage. As a result, when looking at a skull, the nose is missing. The nasal bone is one of a pair of bones that lies under the root and bridge of the nose. The nasal bone articulates superiorly with the frontal bone and laterally with the maxillary bones. Septal cartilage is flexible hyaline cartilage connected to the nasal bone, forming the dorsum nasi. The alar cartilage consists of the apex of the nose; it surrounds the naris.

The nares open into the nasal cavity, which is separated into left and right sections by the nasal septum (Figure). The nasal septum is formed anteriorly by a portion of the septal cartilage (the flexible portion you can touch with your fingers) and posteriorly by the perpendicular plate of the ethmoid bone (a cranial bone located just posterior to the nasal bones) and the thin vomer bones (whose name refers to its plough shape). Each lateral wall of the nasal cavity has three bony projections, called the superior, middle, and inferior nasal conchae. The inferior conchae are separate bones, whereas the superior and middle conchae are portions of the ethmoid bone. Conchae serve to increase the surface area of the nasal cavity and to disrupt the flow of air as it enters the nose, causing air to bounce along the epithelium, where it is cleaned and warmed. The conchae and meatuses also conserve water and prevent dehydration of the nasal epithelium by trapping water during exhalation. The floor of the nasal cavity is composed of the palate. The hard palate at the anterior region of the nasal cavity is composed of bone. The soft palate at the posterior portion of the nasal cavity consists of muscle tissue. Air exits the nasal cavities via the internal nares and moves into the pharynx.

Several bones that help form the walls of the nasal cavity have air-containing spaces called the paranasal sinuses, which serve to warm and humidify incoming air. Sinuses are lined with a mucosa. Each paranasal sinus is named for its associated bone: frontal sinus, maxillary sinus, sphenoidal sinus, and ethmoidal sinus. The sinuses produce mucus and lighten the weight of the skull.

The nares and anterior portion of the nasal cavities are lined with mucous membranes, containing sebaceous glands and hair follicles that serve to prevent the passage of large debris, such as dirt, through the nasal cavity. An olfactory epithelium used to detect odors is found deeper in the nasal cavity.

The conchae, meatuses, and paranasal sinuses are lined by respiratory epithelium composed of pseudostratified ciliated columnar epithelium (Figure). The epithelium contains goblet cells, one of the specialized, columnar epithelial cells that produce mucus to trap debris. The cilia of the respiratory epithelium help remove the mucus and debris from the nasal cavity with a constant beating motion, sweeping materials towards the throat to be swallowed. Interestingly, cold air slows the movement of the cilia, resulting in accumulation of mucus that may in turn lead to a runny nose during cold weather. This moist epithelium functions to warm and humidify incoming air. Capillaries located just beneath the nasal epithelium warm the air by convection. Serous and mucus-producing cells also secrete the lysozyme enzyme and proteins called defensins, which have antibacterial properties. Immune cells that patrol the connective tissue deep to the respiratory epithelium provide additional protection.

View the University of Michigan WebScope to explore the tissue sample in greater detail.

Pharynx

The pharynx is a tube formed by skeletal muscle and lined by mucous membrane that is continuous with that of the nasal cavities (see Figure). The pharynx is divided into three major regions: the nasopharynx, the oropharynx, and the laryngopharynx (Figure).

The nasopharynx is flanked by the conchae of the nasal cavity, and it serves only as an airway. At the top of the nasopharynx are the pharyngeal tonsils. A pharyngeal tonsil, also called an adenoid, is an aggregate of lymphoid reticular tissue similar to a lymph node that lies at the superior portion of the nasopharynx. The function of the pharyngeal tonsil is not well understood, but it contains a rich supply of lymphocytes and is covered with ciliated epithelium that traps and destroys invading pathogens that enter during inhalation. The pharyngeal tonsils are large in children, but interestingly, tend to regress with age and may even disappear. The uvula is a small bulbous, teardrop-shaped structure located at the apex of the soft palate. Both the uvula and soft palate move like a pendulum during swallowing, swinging upward to close off the nasopharynx to prevent ingested materials from entering the nasal cavity. In addition, auditory (Eustachian) tubes that connect to each middle ear cavity open into the nasopharynx. This connection is why colds often lead to ear infections.

The oropharynx is a passageway for both air and food. The oropharynx is bordered superiorly by the nasopharynx and anteriorly by the oral cavity. The fauces is the opening at the connection between the oral cavity and the oropharynx. As the nasopharynx becomes the oropharynx, the epithelium changes from pseudostratified ciliated columnar epithelium to stratified squamous epithelium. The oropharynx contains two distinct sets of tonsils, the palatine and lingual tonsils. A palatine tonsil is one of a pair of structures located laterally in the oropharynx in the area of the fauces. The lingual tonsil is located at the base of the tongue. Similar to the pharyngeal tonsil, the palatine and lingual tonsils are composed of lymphoid tissue, and trap and destroy pathogens entering the body through the oral or nasal cavities.

The laryngopharynx is inferior to the oropharynx and posterior to the larynx. It continues the route for ingested material and air until its inferior end, where the digestive and respiratory systems diverge. The stratified squamous epithelium of the oropharynx is continuous with the laryngopharynx. Anteriorly, the laryngopharynx opens into the larynx, whereas posteriorly, it enters the esophagus.

Larynx

The larynx is a cartilaginous structure inferior to the laryngopharynx that connects the pharynx to the trachea and helps regulate the volume of air that enters and leaves the lungs (Figure). The structure of the larynx is formed by several pieces of cartilage. Three large cartilage pieces—the thyroid cartilage (anterior), epiglottis (superior), and cricoid cartilage (inferior)—form the major structure of the larynx. The thyroid cartilage is the largest piece of cartilage that makes up the larynx. The thyroid cartilage consists of the laryngeal prominence, or “Adam’s apple,” which tends to be more prominent in males. The thick cricoid cartilage forms a ring, with a wide posterior region and a thinner anterior region. Three smaller, paired cartilages—the arytenoids, corniculates, and cuneiforms—attach to the epiglottis and the vocal cords and muscle that help move the vocal cords to produce speech.

The epiglottis, attached to the thyroid cartilage, is a very flexible piece of elastic cartilage that covers the opening of the trachea (see Figure). When in the “closed” position, the unattached end of the epiglottis rests on the glottis. The glottis is composed of the vestibular folds, the true vocal cords, and the space between these folds (Figure). A vestibular fold, or false vocal cord, is one of a pair of folded sections of mucous membrane. A true vocal cord is one of the white, membranous folds attached by muscle to the thyroid and arytenoid cartilages of the larynx on their outer edges. The inner edges of the true vocal cords are free, allowing oscillation to produce sound. The size of the membranous folds of the true vocal cords differs between individuals, producing voices with different pitch ranges. Folds in males tend to be larger than those in females, which create a deeper voice. The act of swallowing causes the pharynx and larynx to lift upward, allowing the pharynx to expand and the epiglottis of the larynx to swing downward, closing the opening to the trachea. These movements produce a larger area for food to pass through, while preventing food and beverages from entering the trachea.

Continuous with the laryngopharynx, the superior portion of the larynx is lined with stratified squamous epithelium, transitioning into pseudostratified ciliated columnar epithelium that contains goblet cells. Similar to the nasal cavity and nasopharynx, this specialized epithelium produces mucus to trap debris and pathogens as they enter the trachea. The cilia beat the mucus upward towards the laryngopharynx, where it can be swallowed down the esophagus.

Trachea

The trachea (windpipe) extends from the larynx toward the lungs (Figurea). The trachea is formed by 16 to 20 stacked, C-shaped pieces of hyaline cartilage that are connected by dense connective tissue. The trachealis muscle and elastic connective tissue together form the fibroelastic membrane, a flexible membrane that closes the posterior surface of the trachea, connecting the C-shaped cartilages. The fibroelastic membrane allows the trachea to stretch and expand slightly during inhalation and exhalation, whereas the rings of cartilage provide structural support and prevent the trachea from collapsing. In addition, the trachealis muscle can be contracted to force air through the trachea during exhalation. The trachea is lined with pseudostratified ciliated columnar epithelium, which is continuous with the larynx. The esophagus borders the trachea posteriorly.

Bronchial Tree

The trachea branches into the right and left primary bronchi at the carina. These bronchi are also lined by pseudostratified ciliated columnar epithelium containing mucus-producing goblet cells (Figureb). The carina is a raised structure that contains specialized nervous tissue that induces violent coughing if a foreign body, such as food, is present. Rings of cartilage, similar to those of the trachea, support the structure of the bronchi and prevent their collapse. The primary bronchi enter the lungs at the hilum, a concave region where blood vessels, lymphatic vessels, and nerves also enter the lungs. The bronchi continue to branch into bronchial a tree. A bronchial tree (or respiratory tree) is the collective term used for these multiple-branched bronchi. The main function of the bronchi, like other conducting zone structures, is to provide a passageway for air to move into and out of each lung. In addition, the mucous membrane traps debris and pathogens.

A bronchiole branches from the tertiary bronchi. Bronchioles, which are about 1 mm in diameter, further branch until they become the tiny terminal bronchioles, which lead to the structures of gas exchange. There are more than 1000 terminal bronchioles in each lung. The muscular walls of the bronchioles do not contain cartilage like those of the bronchi. This muscular wall can change the size of the tubing to increase or decrease airflow through the tube.

Respiratory Zone

In contrast to the conducting zone, the respiratory zone includes structures that are directly involved in gas exchange. The respiratory zone begins where the terminal bronchioles join a respiratory bronchiole, the smallest type of bronchiole (Figure), which then leads to an alveolar duct, opening into a cluster of alveoli.

Alveoli

An alveolar duct is a tube composed of smooth muscle and connective tissue, which opens into a cluster of alveoli. An alveolus is one of the many small, grape-like sacs that are attached to the alveolar ducts.

An alveolar sac is a cluster of many individual alveoli that are responsible for gas exchange. An alveolus is approximately 200 μm in diameter with elastic walls that allow the alveolus to stretch during air intake, which greatly increases the surface area available for gas exchange. Alveoli are connected to their neighbors by alveolar pores, which help maintain equal air pressure throughout the alveoli and lung (Figure).

The alveolar wall consists of three major cell types: type I alveolar cells, type II alveolar cells, and alveolar macrophages. A type I alveolar cell is a squamous epithelial cell of the alveoli, which constitute up to 97 percent of the alveolar surface area. These cells are about 25 nm thick and are highly permeable to gases. A type II alveolar cell is interspersed among the type I cells and secretes pulmonary surfactant, a substance composed of phospholipids and proteins that reduces the surface tension of the alveoli. Roaming around the alveolar wall is the alveolar macrophage, a phagocytic cell of the immune system that removes debris and pathogens that have reached the alveoli.

The simple squamous epithelium formed by type I alveolar cells is attached to a thin, elastic basement membrane. This epithelium is extremely thin and borders the endothelial membrane of capillaries. Taken together, the alveoli and capillary membranes form a respiratory membrane that is approximately 0.5 μm (micrometers) thick. The respiratory membrane allows gases to cross by simple diffusion, allowing oxygen to be picked up by the blood for transport and CO₂ to be released into the air of the alveoli.

DISEASES OF THE…

Respiratory System: AsthmaAsthma is common condition that affects the lungs in both adults and children. Approximately 8.2 percent of adults (18.7 million) and 9.4 percent of children (7 million) in the United States suffer from asthma. In addition, asthma is the most frequent cause of hospitalization in children.

Asthma is a chronic disease characterized by inflammation and edema of the airway, and bronchospasms (that is, constriction of the bronchioles), which can inhibit air from entering the lungs. In addition, excessive mucus secretion can occur, which further contributes to airway occlusion (Figure). Cells of the immune system, such as eosinophils and mononuclear cells, may also be involved in infiltrating the walls of the bronchi and bronchioles.

Bronchospasms occur periodically and lead to an “asthma attack.” An attack may be triggered by environmental factors such as dust, pollen, pet hair, or dander, changes in the weather, mold, tobacco smoke, and respiratory infections, or by exercise and stress.

Symptoms of an asthma attack involve coughing, shortness of breath, wheezing, and tightness of the chest. Symptoms of a severe asthma attack that requires immediate medical attention would include difficulty breathing that results in blue (cyanotic) lips or face, confusion, drowsiness, a rapid pulse, sweating, and severe anxiety. The severity of the condition, frequency of attacks, and identified triggers influence the type of medication that an individual may require. Longer-term treatments are used for those with more severe asthma. Short-term, fast-acting drugs that are used to treat an asthma attack are typically administered via an inhaler. For young children or individuals who have difficulty using an inhaler, asthma medications can be administered via a nebulizer.

In many cases, the underlying cause of the condition is unknown. However, recent research has demonstrated that certain viruses, such as human rhinovirus C (HRVC), and the bacteria Mycoplasma pneumoniae and Chlamydia pneumoniae that are contracted in infancy or early childhood, may contribute to the development of many cases of asthma.

Review

The respiratory system is responsible for obtaining oxygen and getting rid of carbon dioxide, and aiding in speech production and in sensing odors. From a functional perspective, the respiratory system can be divided into two major areas: the conducting zone and the respiratory zone. The conducting zone consists of all of the structures that provide passageways for air to travel into and out of the lungs: the nasal cavity, pharynx, trachea, bronchi, and most bronchioles. The nasal passages contain the conchae and meatuses that expand the surface area of the cavity, which helps to warm and humidify incoming air, while removing debris and pathogens. The pharynx is composed of three major sections: the nasopharynx, which is continuous with the nasal cavity; the oropharynx, which borders the nasopharynx and the oral cavity; and the laryngopharynx, which borders the oropharynx, trachea, and esophagus. The respiratory zone includes the structures of the lung that are directly involved in gas exchange: the terminal bronchioles and alveoli.

The lining of the conducting zone is composed mostly of pseudostratified ciliated columnar epithelium with goblet cells. The mucus traps pathogens and debris, whereas beating cilia move the mucus superiorly toward the throat, where it is swallowed. As the bronchioles become smaller and smaller, and nearer the alveoli, the epithelium thins and is simple squamous epithelium in the alveoli. The endothelium of the surrounding capillaries, together with the alveolar epithelium, forms the respiratory membrane. This is a blood-air barrier through which gas exchange occurs by simple diffusion.

Mechanisms of Breathing

The intra-alveolar and intrapleural pressures are dependent on certain physical features of the lung. However, the ability to breathe—to have air enter the lungs during inspiration and air leave the lungs during expiration—is dependent on the air pressure of the atmosphere and the air pressure within the lungs.

Pressure Relationships

Inspiration (or inhalation) and expiration (or exhalation) are dependent on the differences in pressure between the atmosphere and the lungs. In a gas, pressure is a force created by the movement of gas molecules that are confined. For example, a certain number of gas molecules in a two-liter container has more room than the same number of gas molecules in a one-liter container (Figure 22.15). In this case, the force exerted by the movement of the gas molecules against the walls of the two-liter container is lower than the force exerted by the gas molecules in the one-liter container. Therefore, the pressure is lower in the two-liter container and higher in the one-liter container. At a constant temperature, changing the volume occupied by the gas changes the pressure, as does changing the number of gas molecules. Boyle’s law describes the relationship between volume and pressure in a gas at a constant temperature. Boyle discovered that the pressure of a gas is inversely proportional to its volume: If volume increases, pressure decreases. Likewise, if volume decreases, pressure increases. Pressure and volume are inversely related (P = k/V). Therefore, the pressure in the one-liter container (one-half the volume of the two-liter container) would be twice the pressure in the two-liter container. Boyle’s law is expressed by the following formula:

?1?1=?2?2P1V1=P2V2

In this formula, P₁ represents the initial pressure and V₁ represents the initial volume, whereas the final pressure and volume are represented by P₂ and V_2, respectively. If the two- and one-liter containers were connected by a tube and the volume of one of the containers were changed, then the gases would move from higher pressure (lower volume) to lower pressure (higher volume).

Figure 22.15 Boyle's Law In a gas, pressure increases as volume decreases.

Pulmonary ventilation is dependent on three types of pressure: atmospheric, intra-alveolar, and intrapleural. Atmospheric pressure is the amount of force that is exerted by gases in the air surrounding any given surface, such as the body. Atmospheric pressure can be expressed in terms of the unit atmosphere, abbreviated atm, or in millimeters of mercury (mm Hg). One atm is equal to 760 mm Hg, which is the atmospheric pressure at sea level. Typically, for respiration, other pressure values are discussed in relation to atmospheric pressure. Therefore, negative pressure is pressure lower than the atmospheric pressure, whereas positive pressure is pressure that it is greater than the atmospheric pressure. A pressure that is equal to the atmospheric pressure is expressed as zero.

Intra-alveolar pressure (intrapulmonary pressure) is the pressure of the air within the alveoli, which changes during the different phases of breathing (Figure 22.16). Because the alveoli are connected to the atmosphere via the tubing of the airways (similar to the two- and one-liter containers in the example above), the intrapulmonary pressure of the alveoli always equalizes with the atmospheric pressure.

Figure 22.16 Intrapulmonary and Intrapleural Pressure Relationships Intra-alveolar pressure changes during the different phases of the cycle. It equalizes at 760 mm Hg but does not remain at 760 mm Hg.

Intrapleural pressure is the pressure of the air within the pleural cavity, between the visceral and parietal pleurae. Similar to intra-alveolar pressure, intrapleural pressure also changes during the different phases of breathing. However, due to certain characteristics of the lungs, the intrapleural pressure is always lower than, or negative to, the intra-alveolar pressure (and therefore also to atmospheric pressure). Although it fluctuates during inspiration and expiration, intrapleural pressure remains approximately –4 mm Hg throughout the breathing cycle.

Competing forces within the thorax cause the formation of the negative intrapleural pressure. One of these forces relates to the elasticity of the lungs themselves—elastic tissue pulls the lungs inward, away from the thoracic wall. Surface tension of alveolar fluid, which is mostly water, also creates an inward pull of the lung tissue. This inward tension from the lungs is countered by opposing forces from the pleural fluid and thoracic wall. Surface tension within the pleural cavity pulls the lungs outward. Too much or too little pleural fluid would hinder the creation of the negative intrapleural pressure; therefore, the level must be closely monitored by the mesothelial cells and drained by the lymphatic system. Since the parietal pleura is attached to the thoracic wall, the natural elasticity of the chest wall opposes the inward pull of the lungs. Ultimately, the outward pull is slightly greater than the inward pull, creating the –4 mm Hg intrapleural pressure relative to the intra-alveolar pressure. Transpulmonary pressure is the difference between the intrapleural and intra-alveolar pressures, and it determines the size of the lungs. A higher transpulmonary pressure corresponds to a larger lung.

Physical Factors Affecting Ventilation

In addition to the differences in pressures, breathing is also dependent upon the contraction and relaxation of muscle fibers of both the diaphragm and thorax. The lungs themselves are passive during breathing, meaning they are not involved in creating the movement that helps inspiration and expiration. This is because of the adhesive nature of the pleural fluid, which allows the lungs to be pulled outward when the thoracic wall moves during inspiration. The recoil of the thoracic wall during expiration causes compression of the lungs. Contraction and relaxation of the diaphragm and intercostals muscles (found between the ribs) cause most of the pressure changes that result in inspiration and expiration. These muscle movements and subsequent pressure changes cause air to either rush in or be forced out of the lungs.

Other characteristics of the lungs influence the effort that must be expended to ventilate. Resistance is a force that slows motion, in this case, the flow of gases. The size of the airway is the primary factor affecting resistance. A small tubular diameter forces air through a smaller space, causing more collisions of air molecules with the walls of the airways. The following formula helps to describe the relationship between airway resistance and pressure changes:

?=∆?/?F=∆P/R

As noted earlier, there is surface tension within the alveoli caused by water present in the lining of the alveoli. This surface tension tends to inhibit expansion of the alveoli. However, pulmonary surfactant secreted by type II alveolar cells mixes with that water and helps reduce this surface tension. Without pulmonary surfactant, the alveoli would collapse during expiration.

Thoracic wall compliance is the ability of the thoracic wall to stretch while under pressure. This can also affect the effort expended in the process of breathing. In order for inspiration to occur, the thoracic cavity must expand. The expansion of the thoracic cavity directly influences the capacity of the lungs to expand. If the tissues of the thoracic wall are not very compliant, it will be difficult to expand the thorax to increase the size of the lungs.

Pulmonary Ventilation

The difference in pressures drives pulmonary ventilation because air flows down a pressure gradient, that is, air flows from an area of higher pressure to an area of lower pressure. Air flows into the lungs largely due to a difference in pressure; atmospheric pressure is greater than intra-alveolar pressure, and intra-alveolar pressure is greater than intrapleural pressure. Air flows out of the lungs during expiration based on the same principle; pressure within the lungs becomes greater than the atmospheric pressure.

Pulmonary ventilation comprises two major steps: inspiration and expiration. Inspiration is the process that causes air to enter the lungs, and expiration is the process that causes air to leave the lungs (Figure 22.17). A respiratory cycle is one sequence of inspiration and expiration. In general, two muscle groups are used during normal inspiration: the diaphragm and the external intercostal muscles. Additional muscles can be used if a bigger breath is required. When the diaphragm contracts, it moves inferiorly toward the abdominal cavity, creating a larger thoracic cavity and more space for the lungs. Contraction of the external intercostal muscles moves the ribs upward and outward, causing the rib cage to expand, which increases the volume of the thoracic cavity. Due to the adhesive force of the pleural fluid, the expansion of the thoracic cavity forces the lungs to stretch and expand as well. This increase in volume leads to a decrease in intra-alveolar pressure, creating a pressure lower than atmospheric pressure. As a result, a pressure gradient is created that drives air into the lungs.

Figure 22.17 Inspiration and Expiration Inspiration and expiration occur due to the expansion and contraction of the thoracic cavity, respectively.

The process of normal expiration is passive, meaning that energy is not required to push air out of the lungs. Instead, the elasticity of the lung tissue causes the lung to recoil, as the diaphragm and intercostal muscles relax following inspiration. In turn, the thoracic cavity and lungs decrease in volume, causing an increase in intrapulmonary pressure. The intrapulmonary pressure rises above atmospheric pressure, creating a pressure gradient that causes air to leave the lungs.

There are different types, or modes, of breathing that require a slightly different process to allow inspiration and expiration. Quiet breathing, also known as eupnea, is a mode of breathing that occurs at rest and does not require the cognitive thought of the individual. During quiet breathing, the diaphragm and external intercostals must contract.

A deep breath, called diaphragmatic breathing, requires the diaphragm to contract. As the diaphragm relaxes, air passively leaves the lungs. A shallow breath, called costal breathing, requires contraction of the intercostal muscles. As the intercostal muscles relax, air passively leaves the lungs.

In contrast, forced breathing, also known as hyperpnea, is a mode of breathing that can occur during exercise or actions that require the active manipulation of breathing, such as singing. During forced breathing, inspiration and expiration both occur due to muscle contractions. In addition to the contraction of the diaphragm and intercostal muscles, other accessory muscles must also contract. During forced inspiration, muscles of the neck, including the scalenes, contract and lift the thoracic wall, increasing lung volume. During forced expiration, accessory muscles of the abdomen, including the obliques, contract, forcing abdominal organs upward against the diaphragm. This helps to push the diaphragm further into the thorax, pushing more air out. In addition, accessory muscles (primarily the internal intercostals) help to compress the rib cage, which also reduces the volume of the thoracic cavity.

Respiratory Volumes and Capacities

Respiratory volume is the term used for various volumes of air moved by or associated with the lungs at a given point in the respiratory cycle. There are four major types of respiratory volumes: tidal, residual, inspiratory reserve, and expiratory reserve (Figure 22.18). Tidal volume (TV) is the amount of air that normally enters the lungs during quiet breathing, which is about 500 milliliters. Expiratory reserve volume (ERV) is the amount of air you can forcefully exhale past a normal tidal expiration, up to 1200 milliliters for men. Inspiratory reserve volume (IRV) is produced by a deep inhalation, past a tidal inspiration. This is the extra volume that can be brought into the lungs during a forced inspiration. Residual volume (RV) is the air left in the lungs if you exhale as much air as possible. The residual volume makes breathing easier by preventing the alveoli from collapsing. Respiratory volume is dependent on a variety of factors, and measuring the different types of respiratory volumes can provide important clues about a person’s respiratory health (Figure 22.19).

Figure 22.18 Respiratory Volumes and Capacities These two graphs show (a) respiratory volumes and (b) the combination of volumes that results in respiratory capacity.

Figure 22.19 Pulmonary Function Testing

Respiratory capacity is the combination of two or more selected volumes, which further describes the amount of air in the lungs during a given time. For example, total lung capacity (TLC) is the sum of all of the lung volumes (TV, ERV, IRV, and RV), which represents the total amount of air a person can hold in the lungs after a forceful inhalation. TLC is about 6000 mL air for men, and about 4200 mL for women. Vital capacity (VC) is the amount of air a person can move into or out of his or her lungs, and is the sum of all of the volumes except residual volume (TV, ERV, and IRV), which is between 4000 and 5000 milliliters. Inspiratory capacity (IC) is the maximum amount of air that can be inhaled past a normal tidal expiration, is the sum of the tidal volume and inspiratory reserve volume. On the other hand, the functional residual capacity (FRC) is the amount of air that remains in the lung after a normal tidal expiration; it is the sum of expiratory reserve volume and residual volume (see Figure 22.18).

Respiratory Rate and Control of Ventilation

Breathing usually occurs without thought, although at times you can consciously control it, such as when you swim under water, sing a song, or blow bubbles. The respiratory rate is the total number of breaths, or respiratory cycles, that occur each minute. Respiratory rate can be an important indicator of disease, as the rate may increase or decrease during an illness or in a disease condition. The respiratory rate is controlled by the respiratory center located within the medulla oblongata in the brain, which responds primarily to changes in carbon dioxide, oxygen, and pH levels in the blood.

The normal respiratory rate of a child decreases from birth to adolescence. A child under 1 year of age has a normal respiratory rate between 30 and 60 breaths per minute, but by the time a child is about 10 years old, the normal rate is closer to 18 to 30. By adolescence, the normal respiratory rate is similar to that of adults, 12 to 18 breaths per minute.

Ventilation Control Centers

The control of ventilation is a complex interplay of multiple regions in the brain that signal the muscles used in pulmonary ventilation to contract (Table 22.1). The result is typically a rhythmic, consistent ventilation rate that provides the body with sufficient amounts of oxygen, while adequately removing carbon dioxide.

Summary of Ventilation Regulation

Table22.1

Neurons that innervate the muscles of the respiratory system are responsible for controlling and regulating pulmonary ventilation. The major brain centers involved in pulmonary ventilation are the medulla oblongata and the pontine respiratory group (Figure 22.20).

Figure 22.20 Respiratory Centers of the Brain

The medulla oblongata contains the dorsal respiratory group (DRG) and the ventral respiratory group (VRG). The DRG is involved in maintaining a constant breathing rhythm by stimulating the diaphragm and intercostal muscles to contract, resulting in inspiration. When activity in the DRG ceases, it no longer stimulates the diaphragm and intercostals to contract, allowing them to relax, resulting in expiration. The VRG is involved in forced breathing, as the neurons in the VRG stimulate the accessory muscles involved in forced breathing to contract, resulting in forced inspiration. The VRG also stimulates the accessory muscles involved in forced expiration to contract.

The second respiratory center of the brain is located within the pons, called the pontine respiratory group, and consists of the apneustic and pneumotaxic centers. The apneustic center is a double cluster of neuronal cell bodies that stimulate neurons in the DRG, controlling the depth of inspiration, particularly for deep breathing. The pneumotaxic center is a network of neurons that inhibits the activity of neurons in the DRG, allowing relaxation after inspiration, and thus controlling the overall rate.

Factors That Affect the Rate and Depth of Respiration

The respiratory rate and the depth of inspiration are regulated by the medulla oblongata and pons; however, these regions of the brain do so in response to systemic stimuli. It is a dose-response, negative-feedback relationship in which the greater the stimulus, the greater the response. Thus, increasing stimuli results in forced breathing. Multiple systemic factors are involved in stimulating the brain to produce pulmonary ventilation.

The major factor that stimulates the medulla oblongata and pons to produce respiration is surprisingly not oxygen concentration, but rather the concentration of carbon dioxide in the blood. As you recall, carbon dioxide is a waste product of cellular respiration and can be toxic. Concentrations of chemicals are sensed by chemoreceptors. A central chemoreceptor is one of the specialized receptors that are located in the brain and brainstem, whereas a peripheral chemoreceptor is one of the specialized receptors located in the carotid arteries and aortic arch. Concentration changes in certain substances, such as carbon dioxide or hydrogen ions, stimulate these receptors, which in turn signal the respiration centers of the brain. In the case of carbon dioxide, as the concentration of CO₂ in the blood increases, it readily diffuses across the blood-brain barrier, where it collects in the extracellular fluid. As will be explained in more detail later, increased carbon dioxide levels lead to increased levels of hydrogen ions, decreasing pH. The increase in hydrogen ions in the brain triggers the central chemoreceptors to stimulate the respiratory centers to initiate contraction of the diaphragm and intercostal muscles. As a result, the rate and depth of respiration increase, allowing more carbon dioxide to be expelled, which brings more air into and out of the lungs promoting a reduction in the blood levels of carbon dioxide, and therefore hydrogen ions, in the blood. In contrast, low levels of carbon dioxide in the blood cause low levels of hydrogen ions in the brain, leading to a decrease in the rate and depth of pulmonary ventilation, producing shallow, slow breathing.

Another factor involved in influencing the respiratory activity of the brain is systemic arterial concentrations of hydrogen ions. Increasing carbon dioxide levels can lead to increased H⁺ levels, as mentioned above, as well as other metabolic activities, such as lactic acid accumulation after strenuous exercise. Peripheral chemoreceptors of the aortic arch and carotid arteries sense arterial levels of hydrogen ions. When peripheral chemoreceptors sense decreasing, or more acidic, pH levels, they stimulate an increase in ventilation to remove carbon dioxide from the blood at a quicker rate. Removal of carbon dioxide from the blood helps to reduce hydrogen ions, thus increasing systemic pH.

Blood levels of oxygen are also important in influencing respiratory rate. The peripheral chemoreceptors are responsible for sensing large changes in blood oxygen levels. If blood oxygen levels become quite low—about 60 mm Hg or less—then peripheral chemoreceptors stimulate an increase in respiratory activity. The chemoreceptors are only able to sense dissolved oxygen molecules, not the oxygen that is bound to hemoglobin. As you recall, the majority of oxygen is bound by hemoglobin; when dissolved levels of oxygen drop, hemoglobin releases oxygen. Therefore, a large drop in oxygen levels is required to stimulate the chemoreceptors of the aortic arch and carotid arteries.

The hypothalamus and other brain regions associated with the limbic system also play roles in influencing the regulation of breathing by interacting with the respiratory centers. The hypothalamus and other regions associated with the limbic system are involved in regulating respiration in response to emotions, pain, and temperature. For example, an increase in body temperature causes an increase in respiratory rate. Feeling excited or the fight-or-flight response will also result in an increase in respiratory rate.

DISORDERS OF THE...

Respiratory System: Sleep Apnea

Sleep apnea is a chronic disorder that can occur in children or adults, and is characterized by the cessation of breathing during sleep. These episodes may last for several seconds or several minutes, and may differ in the frequency with which they are experienced. Sleep apnea leads to poor sleep, which is reflected in the symptoms of fatigue, evening napping, irritability, memory problems, and morning headaches. In addition, many individuals with sleep apnea experience a dry throat in the morning after waking from sleep, which may be due to excessive snoring.

There are two types of sleep apnea: obstructive sleep apnea and central sleep apnea. Obstructive sleep apnea is caused by an obstruction of the airway during sleep, which can occur at different points in the airway, depending on the underlying cause of the obstruction. For example, the tongue and throat muscles of some individuals with obstructive sleep apnea may relax excessively, causing the muscles to push into the airway. Another example is obesity, which is a known risk factor for sleep apnea, as excess adipose tissue in the neck region can push the soft tissues towards the lumen of the airway, causing the trachea to narrow.

In central sleep apnea, the respiratory centers of the brain do not respond properly to rising carbon dioxide levels and therefore do not stimulate the contraction of the diaphragm and intercostal muscles regularly. As a result, inspiration does not occur and breathing stops for a short period. In some cases, the cause of central sleep apnea is unknown. However, some medical conditions, such as stroke and congestive heart failure, may cause damage to the pons or medulla oblongata. In addition, some pharmacologic agents, such as morphine, can affect the respiratory centers, causing a decrease in the respiratory rate. The symptoms of central sleep apnea are similar to those of obstructive sleep apnea.

A diagnosis of sleep apnea is usually done during a sleep study, where the patient is monitored in a sleep laboratory for several nights. The patient’s blood oxygen levels, heart rate, respiratory rate, and blood pressure are monitored, as are brain activity and the volume of air that is inhaled and exhaled. Treatment of sleep apnea commonly includes the use of a device called a continuous positive airway pressure (CPAP) machine during sleep. The CPAP machine has a mask that covers the nose, or the nose and mouth, and forces air into the airway at regular intervals. This pressurized air can help to gently force the airway to remain open, allowing more normal ventilation to occur. Other treatments include lifestyle changes to decrease weight, eliminate alcohol and other sleep apnea–promoting drugs, and changes in sleep position. In addition to these treatments, patients with central sleep apnea may need supplemental oxygen during sleep.