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INTRODUCTION 1. Respiration is the exchange of oxygen and carbon dioxide between the air and the cells of

the body. We will consider four aspects of respiration. A. Ventilation is the inflow and outflow of air between the atmosphere and the lungs. B. The exchange of gases between the air and the blood in the lungs, and the exchange of

gases between the blood and the tissues. C. The transport of oxygen and carbon dioxide by blood. D. The regulation of respiration.

2. The respiratory system is involved with acid-base balance. ANATOMY AND HISTOLOGY 1. The respiratory system is responsible for the exchange of gases between the air and the

blood. 2. The respiratory system consists of the lungs and accessory structures. FIGURE 23.1 Nose, Nasal Cavity, Pharynx, and Larynx 1. For the nose, nasal cavity, pharynx, and larynx see the study guide. 2. Almost all of this material is review. Some important are points:

A. The nasal cavity warms, moistens, and filters air. B. The pharynx (throat) connects the nasal cavity with the larynx. C. The larynx is the voice box. Vibrations of the vocal cords, caused by air movement, are

responsible for sound production. 1) The opening of the larynx is covered by the epiglottis, which prevents the entry of

food and liquids into the respiratory tract. 2) All the structures superior to the epiglottis are part of the upper respiratory tract.

All those structures inferior are part of the lower respiratory tract. These are not official anatomical definitions, and there are many definitions. For example, another definition places the larynx in the upper respiratory tract.

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Trachea FIGURE 23.5 1. The trachea is a tube extending from the larynx to the seventh thoracic vertebra.

A. The trachea is held open by C-shaped pieces of cartilage. The cartilage prevent collapse of the trachea during respiration.

B. The ends of the cartilage are connected by smooth muscle, the trachealis muscle.

Contraction of the smooth muscle can decrease the diameter of the trachea. For example, during coughing, the trachea narrows, resulting in more rapid air movement and the expulsion of substances from the trachea.

C. The trachea is lined with mucous-producing, ciliated pseudostratified columnar

epithelium that protects against foreign substances in the lower respiratory tract.

2. The main, or primary bronchi are formed by the division of the trachea. A. One primary bronchus goes to each lung. B. At the separation of the primary bronchi, there is a cartilage ridge called the carina.

Once objects pass the level of the carina, coughing usually stops.

Tracheobronchial Tree FIGURE 23.6 1. The tracheobronchial tree is the inferior part of the respiratory passageways starting with

the trachea. It is formed by a series of dividing tubes that decrease in size but increase in number. A. The trachea divides to form the primary bronchi, which divide to form lobar, or

secondary bronchi (two in the left lung, three in the right lung). The secondary bronchi divide to form segmental, or tertiary bronchi.

B. The bronchi continue to divide and become smaller until small tubes (less than 1 mm in

diameter) called the bronchioles are formed. C. The bronchioles divide several times to produce terminal bronchioles.

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2. Cartilage. A. The trachea and primary bronchi have C-shaped pieces of cartilage. In the secondary

bronchi there are cartilage plates and a layer of smooth muscle. B. Further along, there is less cartilage and more smooth muscle. C. By the time the terminal bronchioles are formed, the cartilage of the tube system is

replaced with smooth muscle. 1) The smooth muscle allows control of the size of the bronchioles, thus regulating air

movement. 2) Constriction of the smooth muscles, during asthma or other allergic reactions can

produce difficulty in breathing.

3. Mucous membrane. The trachea to the terminal bronchioles is lined with various kinds of ciliated mucous epithelium. The mucous traps debris and the cilia move it toward the throat, where it is swallowed.

Conducting and Respiratory Zones 1. The conducting zone is from the nose to the terminal bronchioles. It functions to transport

air to and from the respiratory zone. 2. The respiratory zone extends from the terminal bronchioles to air-filled chambers called

alveoli. The respiratory zone is where gas exchange between the air and the blood takes place.

FIGURE 23.7

A. The terminal bronchioles divide to form respiratory bronchioles, which have a few attached alveoli.

B. The respiratory bronchioles divide to form alveolar ducts, which have many attached

alveoli. It is like a hallway with many open doors. C. The alveolar ducts ends as alveolar sacs, which are chambers with 2 to 3 attached

alveoli.

3. Epithelium. A. The epithelium in the alveolar ducts and alveoli is simple squamous, which facilitates gas

exchange. B. The epithelium in the respiratory zone is not ciliated. Debris is removed by

macrophages.

4. Elastic fibers. The tissue around the alveoli contains elastic fibers, which allow the lungs to expand and then recoil during respiration.

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5. The respiratory membrane is the surfaces of the lungs where gas exchange takes place. It has six parts.

FIGURE 23.8

A. A thin layer of water over the surface of the alveolar wall. B. The wall of the alveolus (simple squamous epithelium).

1) Mostly simple squamous epithelial cells called type I pneumocytes. 2) Surfactant-secreting cells called type II pneumocytes.

C. The basement membrane of the alveolar epithelium. D. A thin interstitial space that may contain connective tissue. E. The basement membrane of the capillary endothelium. F. The wall of the capillary, the endothelium (simple squamous epithelium).

Lungs FIGURE 23.9 1. There are two lungs. Each lung is supplied by a main bronchus. 2. The lungs are divided into lobes. The right lung has three lobes and the left lung has two

lobes. Each lobe is supplied by a lobar bronchus. 3. The lobes are divided into bronchopulmonary segments.

A. The right lung has 10 and the left lung has 9 bronchopulmonary segments. Each bronchopulmonary segment is supplied by a segmental bronchus.

B. The bronchopulmonary segments have their own blood supply and are separated from

each other by connective tissue. A diseased bronchopulmonary segment can be removed and the remaining bronchopulmonary segments can function normally.

4. The bronchopulmonary segments are divided into lobules. The lobules are supplied by the

bronchioles. Thoracic Wall and Muscles of Respiration FIGURE 23.10 1. Changes in the shape of the diaphragm and thoracic cage produce the volume changes

necessary for respiration.

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2. The muscles of inspiration include the diaphragm and muscles that elevate the ribs and sternum. A. The diaphragm is a dome-shaped muscle that forms the inferior boundary of the thoracic

cavity. 1) Contraction of the diaphragm moves the diaphragm inferiorly, increasing the volume

of the thorax. Because the diaphragm has a large surface area (270 cm2) moving the diaphragm a small distance (1 cm) can cause a change in volume of 270 cm3. The diaphragm is the most important muscle of respiration.

2) As inspiration continues, the abdominal organs prevent inferior movement of the

diaphragm. As it continues to contract, the diaphragm causes the ribs to elevate.

B. The external intercostal, scalene, and pectoralis minor muscles also raise the ribs, which increases lateral thoracic volume in the "bucket handle" movement. Elevation of the ribs also pushes out the sternum, increasing the anterior/posterior thoracic volume in the "pump-handle" movement.

FIGURE 23.11 3. The muscles of expiration depress the ribs and sternum and include the internal intercostal

and abdominal muscles. 4. Quiet breathing.

A. During inspiration the diaphragm and external intercostals contract. The abdominal muscles relax, allowing inferior movement of the abdominal organs and the diaphragm.

B. During expiration, the diaphragm and external intercostals relax and passive recoil of the

lungs and thoracic cage decrease thoracic volume. The abdominal muscles contract, moving abdominal organs and the diaphragm superiorly.

5. Labored breathing.

A. During inspiration, muscle contraction is more forceful and all the muscles of inspiration contract.

B. During expiration, the internal intercostal muscles and the abdominal muscles forcefully

contract.

Pleura FIGURE 23.12 1. The lungs are surrounded by the pleural membranes.

A. The visceral pleura is in contact with the lung tissue. The parietal pleura is in contact with the thoracic wall.

B. The pleura cavity is between the visceral and parietal pleurae. The pleural cavity is

filled with pleural fluid.

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2. The pleural fluid has two functions. A. It is a lubricant that prevents friction as the lungs move relative to the thoracic wall. B. It holds the parietal and visceral pleurae together. Thus, the lungs adhere to the inside of

the thoracic wall.

3. Pleurisy is inflammation of the pleural membranes. Blood Supply 1. The pulmonary arteries carry oxygen-poor blood that becomes oxygenated as it passes

through the lungs. The pulmonary veins carry the oxygen-rich blood to the left atrium. 2. Branches of the aorta, the bronchial arteries, supply the tube system of the lungs. They

contain oxygen-rich blood that becomes deoxygenated as it passes through the lungs. The bronchial veins carry the oxygen-poor blood to the azygos system.

3. A small amount of the deoxygenated blood in the bronchial veins mixes with blood in the

pulmonary veins. Consequently the oxygen content of the pulmonary veins decreases. Superior vena cava

Pulmonary vein

Aorta Azygos vein

Heart

Alveolus

Bronchus

Bronchial artery

Bronchial vein

Pulmonary trunk

Deoxygenated blood

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Lymphatic Supply 1. The lymphatic vessels drain excess fluid from the tissues of the lungs.

A. The superficial lymphatic vessels are deep to the visceral pleura and drain the surface of the lungs.

B. The deep lymphatic vessels follow the bronchi.

2. Cancer can spread from the lungs to other tissues through the lymphatic system. VENTILATION Pressure Differences and Air Flow 1. Ventilation is the movement of air into and out of the lungs. 2. The movement of air flow through the tubes of the respiratory passages is similar to blood

flow in a blood vessel. Air flow (F) from an area of higher pressure (P1) to an area of lower pressure (P2) by diffusion is opposed by a resistance (R) to flow.

P1 - P2 F = ------------- R Pressure and Volume 1. Pressure (P) changes as a function of volume (V). According to Boyle’s Law, the pressure

of a gas in a container at constant temperature is k P = ------------ V 2. As volume increases, pressure decreases, whereas as volume decreases, pressure increases. 3. Changes in lung volume are accomplished by changing the volume of the thorax. The lungs,

through the pleural membranes, are attached to the thorax, so a change in thoracic volume produces a change in lung volume.

Air Flow Into and Out of Alveoli 1. Barometric pressure (PB) is air pressure outside of the body.

A. It is usually assigned a value of zero. B. At sea level, actual air pressure is 760 mm Hg. At an altitude of 10,000 feet, air pressure

is 523 mm Hg. Nonetheless, barometric pressure, whatever the altitude, is set at zero. This makes it easier to compare air pressure outside the body with air pressure inside the body.

2. Alveolar pressure (Palv) is the pressure inside the alveoli of the lungs.

A. Alveolar pressure is expressed in centimeters of water relative to barometric pressure. Thus an alveolar pressure of 1 cm H2O is 1 cm H2O greater pressure than barometric pressure, whereas a pressure of -1 cm H2O is -1 cm H2O less pressure than barometric pressure.

B. Alveolar pressure varies depending upon the volume of the thorax.

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3. Keep in mind these relationships: Flow = PB – Palv Palv = k R Valv

A. Air flow into and out of the lungs is a function of barometric pressure and alveolar pressure. Since barometric pressure is constant (zero) that means changing alveolar pressure determines air flow.

B. Alveolar pressure changes because of changes in alveolar volume

3. One cycle of inspiration and expiration. FIGURE 23.13

A. At the end of the expiration, no air is moving into or out of the lungs. Alveolar pressure (0 cm H2O) is equal to barometric pressure (0 cm H2O). B. During inspiration, thoracic volume increases, resulting in an increase in alveolar

volume. Alveolar pressure decreases to -1 cm H2O, which is less than the barometric pressure of 0 cm H2O. Consequently, air moves into the lungs.

C. At the end of inspiration, the thorax stops expanding. Alveolar pressure (0 cm H2O) is

equal to barometric pressure (0 cm H2O) and air movement into the lungs stops. D. During expiration, thoracic volume decreases, resulting in a decrease in alveolar volume.

Alveolar pressure increases to 1 cm H2O, which is greater than the barometric pressure of 0 cm H2O. Consequently, air moves out of the lungs.

E. As expiration ends, the decrease in thoracic volume stops. Go back to step A.

Changing Alveolar Volume 1. Changes in alveolar volume produce the pressure differences responsible for air flow. 2. Lung recoil and pleural pressure cause the alveoli to collapse and expand. Lung Recoil 1. Lung recoil causes the alveoli to collapse.

A. Approximately one-third of lung recoil results from elastic tissue in the lungs. B. The other two-thirds results from water surface tension within the alveoli.

1) Water surface tension is the attraction of water molecules for each other. Remember that water molecules are polar molecules with positive and negative sides to the molecules (see figure 2.6 p. 28).

2) Water tends to take on a droplet form causing the alveolus to collapse and fill with

water (instead of air).

2. Surfactant is a lipoprotein produced by cells within the wall of the alveolus. Surfactant reduces water surface tension and the tendency of the alveolus to collapse.

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3. Respiratory distress syndrome (hyaline membrane disease). A. The ability to produce surfactant is a function of developmental age. Production starts

during the last 1 to 3 months of development. Some full term and many premature babies do not produce enough surfactant.

B. Without adequate surfactant, the force of lung recoil can increase from 4 cm H2O up to 40 cm H2O. C. Increasing thoracic volume causes the lungs to expand and resist the tendency of the

alveoli to collapse. The baby increases thoracic volume with forced, labored inspirations. D. Respiratory distress syndrome can lead to the death of the newborn because of fatigue of

the muscles of respiration. E. Treatment.

1) Pass a tube into the lungs and administer oxygen-rich air under pressure. 2) Administer surfactant in aerosol form. 3) Before birth give the mother cortisol, which stimulates the synthesis of surfactant by

the fetus.

Pleural Pressure 1. Pleural pressure (Ppl) is the pressure in the pleural cavity.

A. Analogy: when you blow into a balloon, the pressure inside the balloon is higher that the pressure outside, and the balloon expands. The same pressure difference can be achieved by decreasing the pressure outside the balloon.

Balloon expands when Pin > Pout B. When the pleural pressure is lower than the alveolar pressure, the alveoli tend to expand. Alveolus expands when Palv > Ppl C. The expansion of the alveoli is opposed by lung recoil. When the force of expansion

cause by the pressure difference is great enough to overcome lung recoil, the alveoli expand.

2. Normally the alveoli are expanded because of a negative pleural pressure that is less than

alveolar pressure. For example, a pleural pressure of -5 cm H2O occurs at the end of expiration. Thus, the pressure difference of 5 cm H2O keeps the alveoli expanded.

Pin Pout

Palv Ppl

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3. Pleural pressure is negative for two reasons. A. A “suction” effect produced as fluid is removed from tissues by the lymphatic system. B. Lung recoil.

1) At rest, when there is no muscle activity causing the thorax to expand, the lungs tend to pull away from the thoracic wall as a result of their tendency to collapse.

2) A negative pleural pressure is produced, much like the pressure produced by pulling

on a syringe.

4. Pneumothorax. A. A pneumothorax is the presence of air or gas in the pleural cavity. B. If a connection is made between the pleural cavity and the atmosphere, air moves into the

pleural cavity and pleural pressure equals barometric pressure (0 cm H2O). C. There is no longer a sufficient pressure difference to overcome lung recoil, and the

alveoli collapse. D. The two pleural cavities are separated from each other (sealed off) by the mediastinum.

So one lung can collapse and the other remain functional. E. Causes of pneumothorax.

1) Openings made through the thoracic wall (broken rib, bullet, knife, etc.). 2) Openings made through the alveoli (lung damage, as in emphysema).

F. Types of pneumothorax. 1) In closed pneumothorax, the initial site of air entry is sealed, gases within the

pleural space are absorbed, and the lung expands as pleural pressure decreases. 2) In open pneumothorax, air continues to collect in the pleural space and the lung

stays collapsed. 3) In tension pneumothorax, air enters the pleural space upon inspiration but doesn't

leave during expiration (the wound forms a flutter valve). Pleural pressure can become greater than barometric pressure (during expiration) causing greater collapse of the lung.

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Alveolar Pressure Changes During Inspiration and Expiration FIGURE 23.14 Events of Inspiration Events of Expiration Muscles of inspiration contract

Muscles of inspiration relax

Thoracic volume

Thoracic volume

Pleural pressure Boyle’s law (volume , pressure ) Lung recoil (negative pressure )

Pleural pressure Boyle’s law (volume , pressure ) Lung recoil (negative pressure )

Alveolar volume (pleural pressure < alveolar pressure)

Alveolar volume (pleural pressure > alveolar pressure)

Alveolar pressure Boyle’s law (volume , pressure )

Alveolar pressure Boyle’s law (volume , pressure )

Air flows into the lungs and lung volume (alveolar pressure < atmospheric pressure)

Air flows out of the lungs and lung volume (alveolar pressure > atmospheric pressure)

MEASURING LUNG FUNCTION Compliance of the Lungs and Thorax 1. Compliance of the lungs and thorax is a measure of how much the volume of the lungs

changes for each unit change in the alveolar pressure. 2. The greater the compliance, the easier it is for the lungs to expand. In emphysema, the elastic tissue in the lungs is destroyed. Does this increase or decrease

compliance?

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Would a baby suffering from respiratory distress syndrome have a higher or lower than normal compliance? Explain.

PHYSICAL PRINCIPLES OF GAS EXCHANGE Partial Pressure 1. Gases move from the air in the alveoli into the blood and from the blood into the tissues by

diffusion. Gases move from areas of higher concentration to areas of lower concentration. 2. In respiratory physiology, the partial pressure of gases is a measure of the concentration of

the gases. Therefore gases move from areas of higher to areas of lower partial pressure. A. Dry air is a mixture of several gases: nitrogen (78%), oxygen (21%), and carbon dioxide

(.04%). At seal level, atmospheric air pressure is 760 mm Hg. B. Dalton's Law: In a mixture of gases the portion of the total pressure that results from

each type of gas is determined by the percentage of the total volume represented by each gas type.

C. The pressure exerted by each gas that makes up the mixture of gases is called the partial

pressure of the gas. 1) The partial pressure of oxygen (PO2) is PO2 = .21 x 760 = 160 mm Hg 2) The partial pressure of carbon dioxide (PCO2) is PCO2 = .0004 x 760 = 0.3 mm Hg 3) In a similar fashion, the partial pressure of nitrogen, water, and other gases can be

calculated. The pressure exerted by gaseous water in a mixture of gases is called water vapor pressure (PH2O).

If water comprised 1% of the gases in air, what would be the water vapor pressure?

Diffusion of Gases Through Liquids 1. When a gas comes into contact with a liquid the gas can dissolve in the liquid. 2. How much gas dissolves in the liquid is expressed by Henry's Law: Concentration = Partial pressure of gas x Solubility coefficient in liquid in air where the solubility coefficient is a measure of how easily the gas dissolves in the liquid.

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3. The solubility coefficient of carbon dioxide is 24 times greater than oxygen. Because gas exchange from the air into the blood involves passage of gases into and out of the layer of water lining the alveoli, this means that carbon dioxide exchange takes place more readily than oxygen exchange.

4. Once the concentrations of the gases in a liquid are known, their partial pressures in the

liquid can be calculated. Diffusion of Gases Through the Respiratory Membrane Diffusion is determined by the distance the gases must move (e.g., the thickness of the respiratory membrane), the diffusion coefficient of the gases, the surface area the gases diffuse through, and the partial pressure (concentration) of the gases. Respiratory Membrane Thickness 1. The smaller the distance a gases has to move, the more rapid the rate of diffusion. 2. The respiratory membrane is very thin to facilitate rapid movement of gases. 3. Diseases that increase the thickness of the respiratory membrane decrease the rate of

diffusion and thus respiratory efficiency. A common cause of increased respiratory membrane thickness is an accumulation of fluid in the alveoli caused by pneumonia or left heart failure.

Diffusion Coefficient 1. The diffusion coefficient is a measure of how fast a gas moves through a substance. The

diffusion coefficient is a function of the solubility coefficient of the gas and the molecular size of the gas.

2. Carbon dioxide has a diffusion coefficient that is 20 times greater than that of oxygen.

A. This means that carbon dioxide diffuses 20 times as rapidly as oxygen for the same conditions.

B. In pneumonia, oxygen exchange is slowed down because of the increased thickness of

the respiratory membrane. Death can occur from lack of oxygen before a buildup of carbon dioxide becomes a problem.

Surface Area 1. The large surface area of the respiratory membrane facilitates gas exchange. The respiratory

membrane is approximately 70 m2, which is approximately the size of the floor area of a 25-by-30-foot room.

2. In some diseases (e.g., emphysema) surface area decreases as a result of the destruction of

the alveoli. Partial Pressure Differences 1. The greater the partial pressure difference of gases across the respiratory membrane, the

greater the rate of gas exchange. 2. Increased metabolism increases the partial pressure differences by increasing blood PCO2 and

lowering blood PO2.

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3. Increased ventilation increases the partial pressure differences by decreasing alveolar PCO2 and increasing alveolar PO2.

Why is oxygen therapy used to treat a patient with pneumonia?

Relationship Between Ventilation and Pulmonary Capillary Blood Flow 1. Normally, alveolar ventilation and capillary blood flow are matched so that the blood

becomes saturated with oxygen and gives off its carbon dioxide. A. If alveolar ventilation decreases, then even though capillary blood flow is normal, there is

inadequate gas exchange. An example is obstruction of the bronchi. B. If capillary blood flow decreases, then even though alveolar ventilation is normal, there is

inadequate gas exchange. An example is decreased cardiac output following a heart attack.

2. Shunted blood is blood that is not completely oxygenated.

A. The anatomic shunt is deoxygenated blood from the bronchi and bronchioles that mixes with the oxygenated blood in the pulmonary veins.

B. The physiologic shunt is deoxygenated blood that is not fully oxygenated as it passes

through the pulmonary capillaries plus the deoxygenated blood from the anatomic shunt. Normally, the physiologic shunt accounts for about 1% - 2% of cardiac output.

C. The physiologic shunt is increased whenever gas exchange between blood and alveolar

air is impaired. For example, decreased air flow through the bronchioles in asthma or decreased diffusion of oxygen across the respiratory membrane in pneumonia.

3. Gravity is normally the most important factor affecting regional blood flow through the

lungs. A. At rest, the inferior parts of the lungs have a greater blood flow than the superior parts.

Increased hydrostatic pressure causes the blood vessels in the inferior parts of the lungs to be expanded, whereas decreased hydrostatic pressure causes the blood vessels in the superior parts of the lungs to be less expanded or even collapsed during diastole.

B. During exercise, cardiac output increases blood flow through the lungs. Blood flow in

the superior parts of the lungs increases the most because the vessels there have a greater ability to expand.

C. Thus, as ventilation increases and the superior parts of the lungs become better

ventilated, there is a corresponding increase in blood flow, and ventilation and blood flow remain matched.

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4. Local control of blood in the lungs. A. Opposite effect of other tissues. A decrease in PO2 causes contraction of the

precapillary sphincters. B. Functional significance. When oxygen levels in the alveoli are low, blood flow is

reduced. Thus, blood is not unnecessarily pumped through lung tissue when there is little oxygen to pick up.

C. High altitude.

1) The PO2 is low because barometric pressure is low (the percent of the air that is oxygen is still approximately 21%). Because of the low PO2, the partial pressure gradient for oxygen is decreased and less oxygen moves into the blood. Altitude Barometric PO2 PO2 Percent Pressure Air Alveoli Saturation 0 760 160 104 97 10,000 523 110 67 90 20,000 349 73 40 70 40,000 141 29 8 5

2) Through local direct control the precapillary sphincters contract because PO2 is decreased in the lungs. This leads to less gas exchange at a time when more is needed.

3) Even people in "good shape" can have high altitude problems.

OXYGEN AND CARBON DIOXIDE TRANSPORT IN THE BLOOD Oxygen and Carbon Dioxide Diffusion Gradients FIGURE 23.16 1. The cells within tissues continually use oxygen, so there is a diffusion gradient for oxygen

from the air to blood to cells. The cells within tissue continually produce carbon dioxide, so there is a diffusion gradient for carbon dioxide from the cells to blood to the air.

2. The diffusion gradients are expressed in terms of the partial pressure (concentration) of the

gases. The PO2 in the alveoli is much lower than the PO2 in the inspired air. Conversely, the PCO2 in

the alveoli is much greater than the PCO2 in the inspired air. Explain.

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Hemoglobin and Oxygen Transport 1. Method of transport of oxygen.

A. Oxygen binds to the heme (iron) portion of hemoglobin in red blood cells. Each hemoglobin molecule can transport four oxygen molecules (O2) and hemoglobin is responsible for 98.5% of oxygen transport.

B. Oxygen dissolved in plasma accounts for 1.5% of oxygen transport.

2. The oxygen-hemoglobin dissociation curve describes the percent saturation of hemoglobin as a function of the partial pressure of oxygen.

FIGURE 23.17

A. Hemoglobin is saturated if all 4 heme sites are carrying oxygen. B. At a PO2 of 70 mm Hg or higher, almost all of the hemoglobin is saturated (95% to 98%).

Because the PO2 in the alveoli is approximately 104 mm Hg, as blood passes through the lungs it becomes saturated with oxygen. Note that the PO2 in the lungs can decrease considerably and hemoglobin is still saturated. Thus, even during exercise hemoglobin is saturated with oxygen.

C. At a PO2 of 40 mm Hg, which is normal for resting tissues, hemoglobin is 75% saturated.

This means that approximately 23% of the oxygen bound to the hemoglobin is released and can diffuse into the tissues.

3. During exercise more oxygen can be released from the blood in tissues.

A. Under conditions of exercise, the PO2 in tissues can drop to 15 mm Hg and hemoglobin is 25% saturated, resulting in a release of 73% of its oxygen.

B. Clearly, the metabolic rate of the tissues (i.e., the PO2 in the tissues) determines the

amount of oxygen released.

Effect of pH, PCO2, and Temperature 1. The Bohr effect.

A. A change in the ability of hemoglobin to bind with oxygen as a result of a change in pH is called the Bohr effect. 1) A decrease in blood pH (i.e., an increase in H+ concentration) decreases the ability of

hemoglobin to bind with oxygen. 2) This occurs because the H+ bind to the hemoglobin and change its shape.

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B. An increase in PCO2 decreases the ability of hemoglobin to bind with oxygen because an increase in carbon dioxide leads to a decrease in pH (increase in hydrogen ion concentration).

CO2 + H2O -------> H2CO3 -------> H+ + HCO3

- Carbon Water Carbonic Hydrogen Bicarbonate dioxide acid ion ion

2. Significance of the Bohr effect. FIGURE 23.18

A. In the tissues, the curve shifts to the right, and hemoglobin releases more oxygen. Cell metabolism produces carbon dioxide. Carbon dioxide levels increase, H+ levels increase, and pH decreases.

B. In the lungs, the curve shifts to the left, and hemoglobin picks up more oxygen.

Carbon dioxide moves out of the blood. Carbon dioxide levels decrease, H+ levels decrease, and pH increases.

Temperature also affects the ability of hemoglobin to carry oxygen. Predict the effect of

an increase in temperature on the ability of hemoglobin to carry oxygen. Explain.

Transport of Carbon Dioxide 1. Method of transport.

A. Approximately 7% is transported dissolved in plasma. B. Approximately 23% is transported bound to proteins in the blood. Proteins that bind to

carbon dioxide are called carbamino [kar-bam′i-nO] compounds. Most of the carbamino compounds are hemoglobin within red blood cell. When carbon dioxide binds to hemoglobin the combination is called carbaminohemoglobin.

C. Approximately 70% of the carbon dioxide in blood is transported as bicarbonate ion.

2. The Haldane effect: hemoglobin that has released its oxygen content binds more readily to carbon dioxide. A. In tissues, hemoglobin releases oxygen and more readily picks up carbon dioxide. B. In the lungs, hemoglobin binds to oxygen and more readily releases carbon dioxide.

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Chloride Shift 1. Basic principle to keep in mind about carbon dioxide transport is that most carbon dioxide

transport depends on this equation. CO2 + H2O <=====> H2CO3 <=====> H+ + HCO3

- Carbon Water Carbonic Hydrogen Bicarbonate Dioxide acid ion ion

A. The reaction is reversible. B. The reaction is an equilibrium in which the ratio of reactants to products stays the same.

1) The result of adding carbon dioxide to the system is the production of more H+ and HCO3

-. 2) When H+ and HCO3

- are removed, it makes it possible for more carbon dioxide to enter the system.

C. In tissues, carbon dioxide is added to the system and H+ and HCO3

- are removed, which increases the amount of carbon dioxide that can be transported as HCO3

-. D. In the lungs, carbon dioxide is removed from the system and H+ and HCO3

- are added.

3. Carbon dioxide transport in tissues. FIGURE 23.19a

A. Carbon dioxide diffuses into red blood cells because tissue PCO2 (45 mm Hg) is greater than blood PCO2 (40 mm Hg).

B. Carbon dioxide combines with water to form carbonic acid. This reaction is facilitated

by an enzyme, carbonic anhydrase, found inside red blood cells. The carbonic acid then dissociates to form H+ and HCO3

-. C. The HCO3

- diffuse out of the red blood cell because there is a higher concentration of HCO3

- inside the red blood cell than outside. In order to maintain electrical neutrality, chloride ions (Cl-) diffuse into the red blood cell. This is called the chloride shift.

D. The H+ combine with hemoglobin. Thus, hemoglobin acts as a buffer because it

prevents a change in pH within the red blood cells.

Result Buffer effect

H+ bind to hemoglobin, which reduces pH change within red blood cells.

Bohr effect

H+ binds to hemoglobin, which changes its shape. Hemoglobin holds less oxygen, the oxygen-hemoglobin dissociation curve shifts to the right, and more oxygen is released to the tissues.

Haldane effect

Hemoglobin that has released oxygen more readily picks up carbon dioxide from the tissues.

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2. Carbon dioxide transport in the lungs. FIGURE 23.19b

A. Carbon dioxide diffuses out of the red blood cell into the alveoli because alveolar PCO2 (40 mm Hg) is less than venous blood PCO2 (45 mm Hg). B. H+ and HCO3

- combine to form carbonic acid which splits to form carbon dioxide and water.

C. HCO3

- diffuse into the red blood cell and Cl- diffuse out to maintain electrical neutrality. D. H+ are released from hemoglobin.

Result Buffer effect

H+ releases hemoglobin, which reduces pH change within red blood cells.

Bohr effect

H+ is released from hemoglobin, which changes its shape. Hemoglobin holds more oxygen, the oxygen-hemoglobin dissociation curve shifts to the left, and hemoglobin picks up more oxygen in the lungs.

Haldane effect

Hemoglobin with oxygen more readily releases carbon dioxide in the lungs.

Carbon Dioxide and Blood pH 1. Blood pH refers to the pH in the plasma, not inside the red blood cells.

A. Carbonic anhydrase is found on the surface of the endothelial cells forming capillaries. B. Thus, carbon dioxide can combine with water, eventually forming hydrogen ions that

change blood pH.

2. The respiratory system can regulate blood pH because changes in respiration rate and depth can change blood carbon dioxide levels.

What effect would hyperventilation have on blood pH?

23-20

What effect would holding one's breath have on blood pH?

RHYTHMIC VENTILATION Respiratory Areas in the Brainstem FIGURE 23.20 1. The medullary respiratory center consists of four collections of neurons.

A. The two dorsal respiratory groups stimulate contraction of the diaphragm. B. The two ventral respiratory groups stimulate the external intercostal, internal

intercostal, and abdominal muscles.

2. The pontine respiratory group is in the pons. It is connected to the medullary respiratory center and appears to play a role in the switching between inspiration and expiration.

Generation of Rhythmic Ventilation 1. Starting inspiration.

A. Certain neurons in the medullary respiratory center spontaneous establish the basic rhythm of respiration.

B. The medullary respiratory center constantly receives input from receptors that monitor

blood gases and the movements of muscles and joints. C. There is also input concerned with voluntary control of respiration and emotions from

other parts of the brain. D. When the input from all sources reaches threshold, inspiration begins.

2. Increasing respiration. Once started, more and more neurons are recruited, resulting in increased stimulation of respiratory muscles and increased respiration.

3. Stopping inspiration. At the same time that neurons are recruited to increase respiration,

other neurons concerned with stopping inspiration are activated. These neurons also receive input from the pontine respiratory group and stretch receptors in the lungs. When their threshold is exceeded, they inhibit the neurons responsible for inspiration. Go back to step 1.

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MODIFICATION OF VENTILATION FIGURE 23.21 Cerebral and Limbic System Control 1. The cerebral cortex can modify respiration during speech and can voluntarily start and stop

respiration. 2. Emotional responses mediated through the limbic system can alter ventilation. For example,

emotional hyperventilation or crying. Chemical Control of Ventilation Chemoreceptors 1. Chemoreceptors respond to changes of chemicals in solution, such as changes in pH or PO2. 2. Central chemoreceptors are located in the chemosensitive area of the medulla oblongata,

and they are connected to the respiratory center. 3. Peripheral chemoreceptors are located in the carotid and aortic bodies. Effect of pH 1. Changes in blood pH cause changes in the pH of the cerebrospinal fluid and thus affect the

chemosensitive area in the medulla oblongata. 2. In response to changes in pH, the chemosensitive area influences the activity of the

respiratory center. 3. Changes in respiration cause changes in blood PCO2 that return blood pH to normal levels. Effect of Carbon Dioxide FIGURE 23.22 1. Carbon dioxide is the major regulator of respiration. It actually controls respiration by

causing changes in blood pH levels that are detected by the chemosensitive area. 2. Hypercapnia is above normal blood PCO2. Hypercapnia = PCO2 , pH . As a result, ventilation , PCO2 , pH . 3. Hypocapnia is lower than normal blood PCO2. Hypocapnia = PCO2 , pH . As a result, ventilation , PCO2 , pH .

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Explain why a person who breathes rapidly and deeply (hyperventilates) for several seconds experiences a short period of time in which respiration does not occur (apnea) before normal breathing resumes.

4. The central chemoreceptors are responsible for most of the response to changes in blood

PCO2 and pH. The peripheral chemoreceptors are responsible for at most 15% - 20% of the response.

Effect of Oxygen 1. The peripheral chemoreceptors responds primarily to low arterial PO2. 2. Action potentials are sent to the medullary respiratory center and the rate and depth of

respiration increases. 3. Normally, the peripheral chemoreceptor reflex is activated only when arterial PO2 falls well

below normal (high altitudes or emergencies such as hemorrhage). This condition is called hypoxia.

The Hering-Breuer Reflex 1. Stretch receptors in the lungs detect stretch of the lungs when they expand. The stretch

receptors send action potential to the respiratory center when the lungs are stretched. 2. The respiratory center is inhibited, inspiration ends, and expiration begins. This mechanism

helps to prevent overexpansion of the lungs. 3. As the lungs collapse, the stretch receptors are no longer stimulated, the respiratory center is

no longer inhibited, and inspiration begins again. 4. In infants, the Hering-Breuer reflex prevents overinflation of the lungs during normal

respiration. In adults, it is normally only important during exercise. Effect of Exercise on Ventilation 1. At the onset of exercise, ventilation increases abruptly.

A. Action potentials from the cerebral cortex motor areas are sent to the skeletal muscles (causing muscle contraction) and to the respiratory center (causing increased ventilation).

B. Movement of the limbs activates proprioceptors that stimulate the respiratory center. C. A close match between respiratory need and respiratory activity is learned. This can be

seen by comparing the respiratory response in a well trained athlete and an untrained individual. The mechanism involved is not known.

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2. Ventilation increases gradually (4-6 minutes) and levels off. A. The mechanisms that increase ventilation at the onset of ventilation probably play a role. B. Normally, the average values of blood PO2, PCO2, and pH change only moderately during

aerobic exercise, despite large changes in oxygen consumption and carbon dioxide production. 1) This means that homeostasis is being maintained. 2) It also means that blood PO2, PCO2, and pH change are not responsible for the greatly

increased respiratory activity, because their average values don't change enough. 3) During exercise, the values of blood PO2, PCO2, and pH rise and fall more than at rest.

These changes may enable the chemoreceptors to "fine tune" the respiratory response during exercise.

C. The anaerobic threshold is the highest level of exercise that can be performed without

causing a significant change in blood pH. Above the anaerobic threshold, the release of lactic acid from skeletal muscle stimulates the peripheral chemoreceptors, resulting in an increase in ventilation.

Other Modifications of Ventilation 1. Ventilation can be altered in response to pain and temperature sensations. 2. Sneeze and cough reflexes alter ventilation. RESPIRATORY ADAPTATIONS TO TRAINING 1. After training, tidal volume and respiratory rate during exercise are greater than before

training. As a result, minute ventilation (tidal volume x respiratory rate) increases. 2. Cardiac efficiency also increases with training. The combined increase in cardiac and

respiratory efficiency increases athletic performance.