1. External Respiration and Internal Respiration Gas Transport External respiration is the actual exchange of gases between the alveoli and the blood (pulmonary gas exchange)
Internal respiration is the gas exchange process that occurs between the systemic capillaries and the tissue cells.
It is important to remember that all gas exchanges are made according to the laws of diffusion; that is, movement occurs toward the area of lower concentration of the diffusing substance.
The relative amounts of O2 and CO2 in the alveolar tissues, and in the arterial and venous blood, are illustrated in the following diagram.

2. Gas exchanges in the body occur according to the laws of diffusion. 

3. External Respiration During external respiration, dark red blood flowing through the pulmonary circuit is transformed into the scarlet river that is returned to the heart for distribution to the systemic circuit.
Although this color change is due to oxygen pickup by hemoglobin in the lungs, carbon dioxide is being unloaded from the blood equally fast.
Because body cells continually remove oxygen from blood, there is always more oxygen in the alveoli than in the blood. Thus, oxygen tends to move from the air of the alveoli through the respiratory membrane into the more oxygen-poor blood of the pulmonary capillaries.
In contrast, as tissue cells remove oxygen from the blood in the systemic circulation, they release carbon dioxide into the blood.
Because the concentration of carbon dioxide is much higher in the pulmonary capillaries than it is in the alveolar air, it will move from the blood into the alveoli and be flushed out of the lungs during expiration.
Relatively speaking, blood draining from the lungs into the pulmonary veins is oxygen-rich and carbon dioxide–poor and is ready to be pumped to the systemic circulation.

4. Gas Transport in the Blood Oxygen is transported in the blood in two ways. Most attaches to hemoglobin molecules inside the RBCs to form oxyhemoglobin —HbO2 . A very small amount of oxygen is carried dissolved in the plasma.
Most carbon dioxide is transported in plasma as the bicarbonate ion (HCO3−).
A smaller amount (between 20 and 30 percent of the transported CO2) is carried inside the RBCs bound to hemoglobin.
Carbon dioxide carried inside the RBCs binds to hemoglobin at a different site than oxygen does.
Before carbon dioxide can diffuse out of the blood into the alveoli, it must first be released from its bicarbonate ion form.
For this to occur, bicarbonate ions must enter the red blood cells where they combine with hydrogen ions (H+) to form carbonic acid (H2CO3). Carbonic acid quickly splits to form water and carbon dioxide, and carbon dioxide then diffuses from the blood into the alveoli.  

5. Diagrammatic representation of the major means of oxygen (O2) and carbon dioxide (CO2) loading and unloading in the body. 
Note that although the conversion of CO2 to bicarbonate ion and the reverse reaction are shown occurring in the plasma in (b), most such conversions occur within the red blood cells. Additionally, though not illustrated, some CO2 is carried within red blood cells bound to hemoglobin.

6. HOMEOSTATIC IMBALANCE
Impaired oxygen transport: Whatever the cause, inadequate oxygen delivery to body tissues is called hypoxia. This condition is easy to recognize in fair-skinned people because their skin and mucosae take on a bluish cast (become cyanotic).
In dark-skinned individuals, this color change can be observed only in the mucosae and nailbeds. Hypoxia may be the result of anemia, pulmonary disease, or impaired or blocked blood circulation.
Carbon monoxide poisoning represents a unique type of hypoxia. Carbon monoxide (CO) is an odorless, colorless gas that competes vigorously with oxygen for the same binding sites on hemoglobin. Because hemoglobin binds to CO faster than to oxygen, carbon monoxide is a very successful competitor—so much so that it crowds out or displaces oxygen.
Carbon monoxide poisoning is the leading cause of death from fire. It is particularly dangerous because it kills its victims softly and quietly. It does not produce the characteristic signs of hypoxia—cyanosis and respiratory distress. Instead, the victim becomes confused and has a throbbing headache. In rare cases, the skin becomes cherry red (the color of the hemoglobin-CO complex), which is often interpreted as a healthy “blush.” People with CO poisoning are given 100 percent oxygen until the carbon monoxide has been cleared from the body.

7. Internal Respiration Internal respiration, the exchange of gases that takes place between the blood and the tissue cells, is the opposite of what occurs in the lungs.
This process, in which oxygen is unloaded and carbon dioxide is loaded into the blood.
Carbon dioxide diffusing out of tissue cells enters the blood.
In the blood, it combines with water to form carbonic acid, which quickly releases the bicarbonate ions. As previously mentioned, most conversion of carbon dioxide to bicarbonate ions actually occurs inside the RBCs, where a special enzyme (carbonic anhydrase) is available to speed up this reaction. Then the bicarbonate ions diffuse out into plasma, where they are transported.
At the same time, oxygen is released from hemoglobin, and the oxygen diffuses quickly out of the blood into the tissue cells.

8. Neural Regulation: Setting the Basic Rhythm Although our tide like breathing seems so beautifully simple, its control is fairly complex.
Neural centers that control respiratory rhythm and depth are located mainly in the medulla and pons.
The medulla, which sets the basic rhythm of breathing, contains a pacemaker, or self-exciting inspiratory center. When its neurons fire, a burst of impulses travels along the phrenic and intercostal nerves to excite the diaphragm and external intercostal muscles.
The medulla also contains an expiratory center that inhibits the pacemaker in a rhythmic way. Impulses going back and forth between the medulla centers maintain a rate of 12–15 respirations/minute. This normal respiratory rate is referred to as eupnea.
Pons centers appear to smooth out the basic rhythm of inspiration and expiration set by the medulla. The bronchioles and alveoli have stretch receptors that respond to extreme over inflation (which might damage the lungs) by initiating protective reflexes. In the case of over inflation, the vagus nerves send impulses from the stretch receptors to the medulla; soon thereafter, inspiration ends and expiration occurs.    During exercise, we breathe more vigorously and deeply because the brain centers send more impulses to the respiratory muscles. This respiratory pattern is called hyperpnea.

9. Non-neural Factors Influencing Respiratory Rate and Depth Physical Factors   Although the medulla’s respiratory centers set the basic rhythm of breathing, there is no question that physical factors such as talking, coughing, and exercising can modify both the rate and depth of breathing. Increased body temperature causes an increase in the rate of breathing. Volition (Conscious Control)   We all have consciously controlled our breathing pattern at one time or another. During singing and swallowing, and many of us have held our breath for short periods to swim underwater.
However, voluntary control of breathing is limited, and the respiratory centers will simply ignore messages from the cortex (our wishes) when the oxygen supply in the blood is getting low or blood pH is falling.
Emotional Factors   Emotional factors also modify the rate and depth of breathing. Have you ever watched a horror movie with bated (held) breath or been so scared by what you saw that you were nearly panting? Have you ever touched something cold and clammy and gasped? All of these result from reflexes initiated by emotional stimuli acting through centers in the hypothalamus.

10. Chemical Factors   Although many factors can modify respiratory rate and depth, the most important factors are chemical—the levels of carbon dioxide and oxygen in the blood.
Increased levels of carbon dioxide and decreased blood pH are the most important stimuli leading to an increase in the rate and depth of breathing.
(Actually, an increase in carbon dioxide levels and decreased blood pH are the same thing in this case, because carbon dioxide retention leads to increased levels of carbonic acid, which decrease the blood pH.)
Changes in carbon dioxide concentrations in the blood seem to act directly on the medulla centers by influencing the pH of cerebrospinal fluid (CSF). Conversely, changes in oxygen concentration in the blood are detected by peripheral chemoreceptor regions in the aorta (aortic body in the aortic arch) and in the fork of the common carotid artery.
These, in turn, send impulses to the medulla when blood oxygen levels are dropping. Although every cell in the body must have oxygen to live, it is the body’s need to rid itself of carbon dioxide (not to take in oxygen) that is the most important stimulus for breathing in a healthy person. Decreases in oxygen levels become important stimuli only when the levels are dangerously low.

11. REVIEW
Which type of cellular transport moves respiratory gases between the blood and the body’s cells?
Diffusion
What is the major form in which CO2 is transported in the blood?
As bicarbonate ion.
What is cyanosis?
Cyanosis is a bluish cast to the skin and nails due to inadequate oxygenation of the blood.
Which brain area is most important in setting the basic respiratory rate and rhythm?
The medulla

12. 15. What do TV, ERV, and VC mean?
TV: Tidal volume; the amount of air inspired or expired during a normal breath. ERV: Expiratory reserve volume; the amount of air that can be forcibly exhaled beyond a normal tidal expiration. VC: Vital capacity; total exchangeable air.
16. Name several non-respiratory air movements, and explain how each differs from normal
breathing.
All nonrespiratory air movements are described in Table 13.1.
17. The contraction of the diaphragm and the external intercostal muscles begins inspiration.
What happens, in terms of volume and pressure changes in the lungs, when these muscles
contract?
When the diaphragm contracts, it moves inferiorly, thereby increasing the intrathoracic volume in the superior-inferior dimension. The contraction of the external intercostal muscles elevates the rib cage, increasing the intrathoracic volume in the anterior-posterior and lateral dimensions. As the intrathoracic volume is increased, the intrapulmonary pressure decreases.
18. What is the major way that oxygen is transported in the blood?
Oxygen is mainly transported bound to hemoglobin within RBCs.

13. 19. What determines in which direction carbon dioxide and oxygen will diffuse in the lungs? In
the tissues?
Gases diffuse according to their concentration gradients, that is, from an area of their higher concentration to an area of their lower concentration. Venous blood is high in carbon dioxide and low in oxygen compared to alveolar air; thus, carbon dioxide tends to leave the pulmonary blood to enter the alveolar air, and oxygen tends to move from the alveoli into the pulmonary capillary blood. Arterial blood is high in oxygen and low in carbon dioxide; thus, the diffusion gradient in the tissues is opposite to that in the lungs.
20. Name the two major brain areas involved in the nervous control of breathing.
Medulla (inspiratory and expiratory centers) and pons (apneustic and pneumotaxic centers).
21. Name three physical factors that can modify respiratory rate or depth.
Talking, coughing (and other types of nonrespiratory air movements), exercise, and increased body temperature.
22. Name two chemical factors that modify respiratory rate and depth. Which is usually more
important?
Decreases in oxygen content of the blood and changes in carbon dioxide blood concentration (leading to increased or decreased blood pH). The latter factor is much more important in respiratory control.

14. 23. Define hyperventilation
23. Define hyperventilation. If you hyperventilate, do you retain or expel more carbon dioxide?
What effect does hyperventilation have on blood pH? On breathing rate?
Hyperventilation is rapid, deep breathing. During hyperventilation more carbon dioxide is expelled. Since this decreases the carbonic acid content of the blood, the blood pH increases (becomes more alkaline). To counteract this effect, the breathing rate must be decreased.
24. Compare and contrast the signs and symptoms of emphysema and chronic bronchitis.
In emphysema, the individual has problems exhaling due to loss of elasticity of the lungs. Consequently, expiration becomes an active process, and the person is always tired. A barrel chest develops from air retention, but cyanosis is a late sign. In chronic bronchitis, inspiration is a problem because the respiratory passages are narrowed by the inflamed mucosa and excessive mucus. Infections are common because mucus pools in the lungs. Cyanosis occurs early in the disease.
25. After putting her 1-year-old boy (who puts virtually everything in his mouth) down for a nap, a mother failed to find one of the larger beads she used to make the custom jewelry she produces for sale. Two days later, the boy developed a cough and became feverish. What is likely to have happened to the bead, and where (anatomically) would you expect it to be found?
The boy most likely swallowed the bead and it entered the respiratory tract. It could probably be found in the right primary bronchus.

15. 26. Why doesn’t Mom have to worry when 3-year-old Johnny threatens to “hold his breath till he
dies”?
Voluntary control of breathing is limited by the body’s need to obtain oxygen and get rid of carbon dioxide. When these processes are impaired, involuntary controls take over.
27. Mr. Rasputin bumped a bee’s nest while making repairs on his roof. Not surprisingly, he was
promptly stung several times. Because he knew he was allergic to bee stings, he rushed to
the hospital. While waiting, he went into a state of shock and had extreme difficulty
breathing. Examination showed his larynx to be edematous, and a tracheostomy was
performed. Why is edema of the larynx likely to obstruct the airway? What is a tracheostomy,
and what purpose does it serve?
The larynx functions to provide an open airway to the trachea and lungs. Edematous swelling of the mucosa of the larynx would close the airway, blocking all air entering the trachea. Tracheotomy is a surgical incision into the trachea through the anterior neck. It allows air to reach the lungs when the larynx is blocked.