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a
Level: 1

1. Ventilation refers to the
A) movement of air into and out of the lungs.
B) gas exchange between the blood and the tissues.
C) transportation of oxygen and carbon dioxide in the blood.
D) gas exchange between the air in the lungs and the blood.
E) respiration at the cellular level.

d
Level: 1

2. Internal respiration refers to
A) atmospheric air coming into the lungs.
B) gas exchange between the lungs and the blood.
C) gas exchange in the atmosphere.
D) gas exchange between the blood and body tissues.
E) cellular respiration.

b
Level: 1

3. Which of the following is part of the upper respiratory tract?
A) larynx
B) pharynx
C) trachea
D) bronchi
E) bronchioles

e
Level: 1

4. The nasal septum
A) divides the nose into superior and inferior chambers.
B) forms the floor of the nasal cavity.
C) is the opening of the nose to the outside environment.
D) is the part of the nose responsible for the sense of smell.
E) divides the nose into right and left chambers.

e
Level: 1

5. Which of the following functions is associated with the nose?
A) initiating the cough reflex
B) external respiration
C) warming the air
D) producing mucus to trap debris from the air
E) C and D

a
Level: 1

6. Which of the following structures opens directly into the nasal cavity?
A) paranasal sinuses
B) auditory tubes
C) lacrimal glands
D) fauces
E) epiglottis

a
Level: 1

7. Whenever people cry, their nose runs. This is because the _____ drain tears into the nose.
A) nasolacrimal ducts
B) paranasal sinuses
C) lacrimal glands
D) Wharten's ducts
E) auditory tube

a
Level: 1

8. The olfactory epithelium responsible for the sense of smell is located in the
A) roof of the nasal cavity.
B) wall of the nasal septum.
C) lining of the nasopharynx.
D) cavity of the paranasal sinuses.
E) floor of the nasal cavity.

d
Level: 2

9. A molecule of air enters the nose through the external nares. Which of the following is the correct pathway to the trachea?
A) nasal cavity, larynx, pharynx, trachea
B) oral cavity, nasal cavity, larynx, pharynx, trachea
C) nasopharynx, nasal cavity, laryngopharynx, trachea
D) nasal cavity, pharynx, larynx, trachea
E) nasal cavity, trachea, larynx, pharynx

c
Level: 1

10. Which of the following is a passageway for both air and food?
A) trachea
B) larynx
C) pharynx
D) bronchus
E) esophagus

b
Level: 1

11. The portion of the pharynx that extends from the internal nares to the level of the uvula is the
A) glottis.
B) nasopharynx.
C) oropharynx.
D) laryngopharynx.
E) glottopharynx

c
Level: 1

12. The auditory tubes open into the
A) fauces.
B) oropharynx.
C) nasopharynx.
D) laryngopharynx.
E) nasal cavity.

b
Level: 1

13. The largest of the laryngeal cartilages is the
A) epiglottis.
B) thyroid cartilage.
C) cricoid cartilage.
D) corniculate cartilage.
E) cuneiform cartilage.

c
Level: 1

14. The ring of cartilage that forms the base of the larynx is the
A) epiglottis.
B) thyroid cartilage.
C) cricoid cartilage.
D) arytenoid cartilage.
E) cuneiform cartilage.

b
Level: 1

15. Which of the following statements concerning the larynx is correct?
A) The larynx contains four unpaired cartilages.
B) When the glottis closes, air is prevented from leaving the lungs.
C) Unlike other portions of the larynx, the epiglottis consists of some bony tissue.
D) The inferior laryngeal cartilage is the thyroid cartilage.
E) The epiglottis is also called "Adam's apple".

a
Level: 1

16. During swallowing, the opening into the larynx is covered by the
A) epiglottis.
B) thyroid cartilage.
C) cricoid cartilage.
D) arytenoid cartilage.
E) the "Adam's apple".

d
Level: 1

17. Which of the following laryngeal cartilages are paired?
1. epiglottis
2. thyroid cartilage
3. corniculate cartilage
4. arytenoid cartilage
5. cuneiform cartilage
6. cricoid cartilage
A) 1, 2, 6
B) 3, 5, 6
C) 2, 4, 5
D) 3, 4, 5
E) 2, 3, 4

b
Level: 1

18. When these ligaments or folds come together, they prevent food from entering the larynx.
A) vocal cords
B) vestibular folds
C) cricothyroid ligaments
D) epiglottic folds
E) vocal folds

e
Level: 1

19. When air passes through the glottis, which structures vibrate to produce sound?
A) thyroid folds
B) ventricular folds
C) epiglottal cords
D) cricohyoid folds
E) vocal folds (cords)

a
Level: 1

20. The pitch of the sound produced by the vocal cords is controlled by the
A) frequency of the vibrations.
B) amplitude of the vibrations.
C) thickness of the thyroid cartilage.
D) size of the glottis.
E) force of air moving past them.

b
Level: 1

21. The trachea
A) is located in the pleural cavity.
B) has "C" shaped cartilages that form its anterior and lateral sides.
C) is lined with keratinized squamous epithelium.
D) bifurcates to form the bronchioles.
E) collapses when not in use.

b
Level: 1

22. The respiratory zone of the tracheobronchial tree includes which of the following?
A) trachea
B) alveoli
C) primary bronchi
D) larynx
E) tertiary bronchi

b
Level: 1

23. Each lobe of each lung is supplied by a
A) primary bronchus.
B) secondary bronchus.
C) tertiary bronchus.
D) bronchiole.
E) segmental bronchus.

d
Level: 1

24. Of the following structures, the largest in diameter is the
A) primary bronchus.
B) secondary bronchus.
C) respiratory bronchiole.
D) trachea.
E) tertiary bronchus.

c
Level: 2

25. Arrange the following structures in the order air passes through them during inhalation:
1. alveolar ducts
2. alveolus
3. respiratory bronchiole
4. terminal bronchiole
A) 1, 2, 3, 4
B) 2, 1, 3, 4
C) 4, 3, 1, 2
D) 3, 2, 1, 4
E) 4, 3, 2, 1

c
Level: 3

26. When people aspirate liquids or food into their lungs, the liquid or food most commonly enters the right lung rather than the left lung. This is because the right primary bronchus is __________ than the left primary bronchus.
A) longer
B) thinner
C) more vertical
D) less ciliated
E) shorter

a
Level: 1

27. The diameter of bronchioles can change because their walls contain
A) smooth muscle.
B) skeletal muscle.
C) fibrous cartilage.
D) hyaline cartilage.
E) elastic cartilage.

d
Level: 2

28. From largest to smallest, the correct sequence for the following passageways is
A) bronchi, bronchioles, respiratory bronchioles, terminal bronchioles, alveoli.
B) bronchioles, terminal bronchioles, respiratory bronchioles, bronchi, alveoli.
C) alveoli, bronchioles, terminal bronchioles, respiratory bronchioles, bronchi.
D) bronchi, bronchioles, terminal bronchioles, respiratory bronchioles, alveoli.
E) terminal bronchioles, respiratory bronchioles, bronchi, bronchioles, alveoli

a
Level: 1

29. Gas exchange between the air in the lungs and the blood takes place in the
A) alveoli.
B) primary bronchi.
C) terminal bronchioles.
D) trachea.
E) respiratory bronchi.

b
Level: 2

30. Constriction of smooth muscle in the bronchioles
A) occurs during periods of exercise.
B) restricts the flow of air into the lungs.
C) decreases ciliary action.
D) increases airflow out of the lungs.
E) does not affect airflow.

a
Level: 1

31. The walls of the alveoli
A) are composed of simple squamous epithelium.
B) contain several layers of smooth muscle.
C) contain goblet cells.
D) are surrounded by cartilage.
E) are ciliated.

c
Level: 3

32. A person has severe damage or disease in the upper area of their right lung. Surgery is necessary. The doctor would need to remove
A) the entire right lung.
B) the superior lobe of the right lung.
C) the apical bronchopulmonary segment of the right lung.
D) only the damaged area of the apical bronchopulmonary segment.
E) the apical, anterior, and posterior segments of the superior lobe.

b
Level: 1

33. Which of the following statements regarding the lungs is correct?
A) The left lung is larger than the right lung.
B) The left lung contains two lobes while the right lung contains three lobes.
C) The left lung has more bronchopulmonary segments than the right lung.
D) Only the right lung has a hilum.
E) The left lung contains three lobes while the right lung contains two lobes.

a
Level: 2

34. Which of the following muscles increases the volume of the thorax during a normal inhalation?
1. diaphragm
2. external intercostals
3. internal intercostals
4. rectus abdominis
A) 1, 2
B) 1, 3
C) 2, 3
D) 2, 4
E) 3, 4

c
Level: 2

35. Contraction of the _______ will increase the superior-inferior dimension of the thoracic cavity.
A) rectus abdominis
B) internal intercostals
C) diaphragm
D) external intercostals
E) sternocleidomastoid

d
Level: 2

36. Expiration during quiet breathing
A) is an active process.
B) requires more muscle contractions than inspiration.
C) is due to contraction of the diaphragm and elevation of the ribs.
D) occurs when the diaphragm and external intercostal muscles relax.
E) is not affected by the elastic properties of the lungs.

a
Level: 1

37. Which of the following statements concerning the lungs and the pleura is true?
A) Each lung is suspended in a separate pleural cavity.
B) Parietal pleura covers the surface of each lung.
C) The space between the visceral and parietal pleurae is called the mediastinum.
D) The pleural fluid assists in gas exchange.
E) The pleural membranes adhere, but cannot slide past each other.

c
Level: 1

38. The serous membranes that surround the lungs are called the
A) mucous membranes.
B) synovial membranes.
C) pleural membranes.
D) peritoneal membranes.
E) pulmonary membranes.

b
Level: 1

39. Oxygenated blood is carried to the tissues of the lungs via the
A) pulmonary veins.
B) bronchial arteries.
C) pulmonary artery.
D) abdominal aorta.
E) pleural arteries.

d
Level: 1

40. The lungs have
A) one blood flow route and one lymphatic supply.
B) two blood flow routes and one lymphatic supply.
C) one blood flow route and two lymphatic supplies.
D) two blood flow routes and two lymphatic supplies.
E) three blood flow routes and one lymphatic supply.

a
Level: 1

41. When the inspiratory muscles contract,
A) thoracic volume increases.
B) pleural pressure increases.
C) the alveolar pressure increases.
D) expiration occurs.
E) thoracic volume decreases.

d
Level: 2

42. Which of the following statements is true?
A) As thoracic volume increases, alveolar pressure (Palv) increases.
B) In expiration, the thoracic volume increases.
C) Constriction of bronchioles assists breathing.
D) As alveolar volume increases, alveolar pressure (Palv) decreases.
E) Pressure is directly proportional to volume.

c
Level: 1

43. For air to flow into or out of the lungs, there must be
A) a volume gradient established between the atmosphere and the alveoli.
B) a temperature gradient between the atmosphere and the alveoli.
C) a pressure gradient established between the atmosphere and the alveoli.
D) a diffusion gradient between the atmosphere and the alveoli.
E) none of the above

a
Level: 2

44. During expiration, the alveolar pressure must be
A) greater than atmospheric pressure.
B) less than atmospheric pressure.
C) equal to atmospheric pressure.
D) greater than pleural pressure.
E) none of the above

a
Level: 2

45. Surfactant facilitates alveolar ventilation by
A) decreasing the surface tension between water molecules on the lining of the alveoli.
B) decreasing thoracic compliance.
C) attracting water to the alveolar surface.
D) increasing the surface area for gas exchange.
E) increases the surface tension between fluid and the alveoli.

c
Level: 3

46. During inspiration, contraction of the diaphragm causes the volume of Mr. Jones' thoracic cavity to increase and the pleural pressure to decrease. The pressure in his alveoli (Palv) will
A) decrease below atmospheric pressure (PB), causing air to move out of his lungs.
B) become greater than atmospheric pressure (PB), causing air to move into his lungs.
C) decrease below atmospheric pressure (PB), causing air to move into his lungs.
D) become greater than atmospheric pressure (PB), causing air to move out of his lungs.
E) does not change.

a
Level: 2

47. Which of the following factors keeps the alveoli expanded?
A) positive alveolar pressure
B) positive pleural pressure
C) constriction of the bronchioles
D) elastic recoil of the lungs
E) negative alveolar pressure

c
Level: 1

48. Air in the pleural cavity is called
A) emphysema.
B) respiratory distress syndrome.
C) a pneumothorax.
D) pneumonia.
E) forced expiration.

c
Level: 2

49. In which of the following situations is compliance greatest?
A) collapse of the alveoli
B) airway obstruction
C) emphysema
D) pulmonary fibrosis
E) pulmonary edema

a
Level: 1

50. Which of the following individuals will have the highest vital capacity?
A) a well-trained athlete (male or female)
B) a middle-aged, short female
C) an 80-year-old male
D) a young, obese male
E) an adult female.

e
Level: 1

51. Mr. Huff and Puff exhales normally; then, using forced expiration, he exhales as much air as possible. The volume of air still remaining in his lungs is called
A) expiratory reserve volume.
B) tidal volume.
C) inspiratory reserve volume.
D) vital capacity.
E) residual volume.

b
Level: 1

52. The volume of air available for gas exchange per minute is called the
A) vital capacity.
B) alveolar ventilation.
C) minute respiratory volume.
D) functional residual capacity.
E) respiratory rate.

b
Level: 1

53. Physiological dead air space is anatomic dead space plus
A) the residual volume.
B) the volume of any alveoli where gas exchange is diminished.
C) the volume of blood flowing to the lungs.
D) the respiration rate.
E) tidal volume.

c
Level: 3

54. Calculate the alveolar ventilation if the tidal volume is 500 ml., the respiratory rate is 12/minute, and the anatomical dead space is 100 ml.
A) 1200 ml
B) 1800 ml
C) 4800 ml
D) 6000 ml
E) 7200 ml

d
Level: 3

55. If the total pressure of a mixture of gases was 760 mm Hg and its composition is 20% oxygen, 0.04% carbon dioxide, 75% nitrogen, and 5% water vapor, then the partial pressure of oxygen would be
A) 740 mm Hg.
B) 20 mm Hg.
C) 148 mm Hg.
D) 152 mm Hg.
E) 200 mm Hg.

b
Level: 1

56. Oxygen and carbon dioxide are exchanged across the respiratory membrane by the process of
A) active transport.
B) diffusion.
C) filtration.
D) osmosis.
E) cotransport.

c
Level: 2

57. Which of the following increases the rate of gas exchange across the respiratory membrane?
A) increased fluid in the alveoli
B) increased thickness of the respiratory membrane
C) increased surface area of the respiratory membrane
D) increased connective tissue in the alveolar wall
E) decreased surface area of the respiratory membrane

e
Level: 2

58. Which of the following respiratory membrane layers is closest to air in the alveolus?
A) alveolar epithelium
B) alveolar basement membrane
C) capillary basement membrane
D) capillary endothelium
E) alveolar fluid (with surfactant)

b
Level: 1

59. Which of the following results in an increase in shunted blood (blood not completely oxygenated)?
A) exercise
B) pulmonary edema
C) increased heart rate
D) increased respiration rate
E) none of the above

b
Level: 2

60. As the result of an asthmatic attack,
A) ventilation exceeds the ability of blood to pick up oxygen.
B) ventilation is inadequate to oxygenate blood.
C) pulmonary blood flow is reduced while ventilation remains normal.
D) the surface area available for gas exchange increases.
E) bronchioles dilate.

d
Level: 3

61. Arrange the following in order from highest to lowest PO2.
1. PO2 of pulmonary veins
2. PO2 of pulmonary artery
3. PO2 of alveolar air
A) 1, 2, 3
B) 2, 1, 3
C) 2, 3, 1
D) 3, 1, 2
E) 3, 2, 1

a
Level: 2

62. Oxygen diffusion from the alveolus to the pulmonary capillary occurs because
A) alveolar PO2 is greater than capillary PO2.
B) oxygen diffuses faster than carbon dioxide.
C) alveolar PCO2 is greater than capillary PCO2.
D) alveolar PO2 is less than capillary PCO2.
E) carbon dioxide diffuses faster than oxygen.

d
Level: 2

63. In which of the following sequences does PO2 progressively decrease?
A) body tissue, arterial blood, alveolar air
B) body tissue, alveolar air, arterial blood
C) blood in aorta, atmospheric air, body tissues
D) atmospheric air, blood in aorta, body tissues
E) body tissue, aorta, alveolar air

a
Level: 1

64. Oxygen is transported in the blood
A) bound to hemoglobin.
B) bound to albumin.
C) in combination with inorganic ions.
D) as part of the bicarbonate ion.
E) dissolved in the plasma.

a
Level: 2

65. During exercise, the oxygen-hemoglobin dissociation curve
A) shifts to the right.
B) shifts to the left.
C) doesn't shift.

c
Level: 1

66. The Bohr effect refers to the
A) mechanism involved in diffusion of nitrogen into the blood.
B) physical laws governing the solubility of gases in fluids.
C) effect of pH on the oxygen-hemoglobin dissociation curve.
D) chemical equilibrium between carbonic acid and bicarbonate in the blood.
E) effect of temperature on the oxygen-hemoglobin dissociation curve.

b
Level: 2

67. Most oxygen is carried in the blood ______; but most carbon dioxide is carried ________.
A) dissolved in plasma/associated with salt or acid
B) bound to hemoglobin/associated with bicarbonate ions
C) combined with albumin/associated with carbonic acid
D) bound to hemoglobin/bound to albumin
E) bound to plasma proteins/as carbon dioxide

a
Level: 3

68. Mr. Jones has a pH of 7.25 and a temperature of 100.5°F. His oxygen-hemoglobin dissociation curve would
A) shift to the right, causing more O2 to be released to his cells.
B) shift to the left, allowing less O2 to be released to his cells.
C) show no change, allowing the O2 concentration to remain stable.

c
Level: 1

69. When 2, 3 biphosphoglycerate (BPG) levels increase, hemoglobin
A) releases less oxygen to tissues.
B) releases more carbon dioxide to tissues.
C) releases more oxygen to tissues.
D) releases less carbon dioxide to tissues.
E) none of the above

a
Level: 1

70. Most carbon dioxide is transported in the blood
A) in the form of bicarbonate ions.
B) bound to carbamino compounds.
C) dissolved in the plasma.
D) by the leukocytes.
E) in the form of carbonic acid.

c
Level: 2

71. Hemoglobin that has released its oxygen
A) loses its affinity for oxygen.
B) will dissolve in the plasma.
C) will bind more readily to carbon dioxide.
D) is broken down to heme and globin and excreted.
E) will bind more readily to oxygen.

b
Level: 1

72. The chloride shift refers to the
A) effect of chloride ions on the oxygen dissociation curve.
B) exchange of chloride ions for bicarbonate ions across the red blood cell membrane.
C) exchange of chloride ions for carbon dioxide across alveolar cell membranes.
D) effect of chloride ions on hydrogen ion diffusion from red blood cells.
E) exchange of chloride ions for hemoglobin across the RBC membrane.

c
Level: 2

73. Which of the following events in the chloride shift occurs last?
A) Carbon dioxide diffuses into a red blood cell.
B) Carbonic acid dissociates to form bicarbonate and hydrogen ions.
C) Bicarbonate ions diffuse into the plasma.
D) CO2 and H2O  H2CO3
E) Carbonic acid dissociates to form water and carbon dioxide.

b
Level: 2

74. Which of the following molecules acts as a buffer during the chloride shift?
A) carbon dioxide
B) hemoglobin
C) carbonic anhydrase
D) water
E) bicarbonate ion

a
Level: 2

75. If there is an accumulation of acidic products in the plasma, one would expect
A) an increase in respiration rate.
B) a decrease in respiration rate.
C) no influence on respiration rate.
D) an increase in residual volume.
E) apnea.

b
Level: 2

76. Direct stimulation of neurons within the dorsal respiratory group would cause an increase in the frequency of action potential in the
A) glossopharyngeal nerve that innervates the pharyngeal muscles.
B) phrenic nerve that innervates the diaphragm.
C) vagus nerve that innervates the smooth muscle of the bronchioles.
D) intercostal nerves to internal intercostals muscles.
E) intercostal nerves to external intercostals muscles.

a
Level: 1

77. Which of the following statements concerning the dorsal and ventral respiratory groups is false?
A) They are located in the reticular activating system.
B) There is cross communication between these two groups.
C) These groups establish the basic rate and depth of breathing.
D) These groups increase the number of action potentials to the respiratory muscles during inspiration.
E) Two dorsal and two ventral respiratory groups make up the medullary respiratory center.

b
Level: 1

78. The ventral respiratory group
A) is located in the pons.
B) stimulates the intercostal and abdominal muscles.
C) is part of the pontine respiratory group.
D) is active only in exhalation.
E) stimulates the diaphragm.

d
Level: 1

79. The pontine respiratory neurons
A) are located in the medulla oblongata in the brain.
B) are active only during inspiration.
C) are active only during expiration.
D) play a role in switching between inspiration and expiration.
E) is essential for respiratory rhythm.

c
Level: 2

80. Rhythmicity of breathing involves
A) conscious effort and control.
B) stimulation of inspiration. Expiration is automatic.
C) integration of stimuli that start and then stop inspiration.
D) a set pattern of inspiration - expiration that is always the same.
E) regulation of stimuli that start inspiration and stop expiration.

d
Level: 2

81. A baby holding its breath will
A) be termed a "blue baby".
B) have brain cells damaged because of low blood oxygen levels.
C) suffer heart damage because of increased pressure in the aorta.
D) automatically start to breathe when the CO2 levels in the blood reach a high enough value.
E) automatically start to breathe when oxygen levels decrease slightly.

e
Level: 1

82. The chemosensitive area of the brain is located in the
A) pons.
B) cerebral peduncles.
C) cerebellum.
D) hypothalamus.
E) medulla.

d
Level: 2

83. Mr. Smith hypoventilates and retains too much carbon dioxide. Which of the following receptors is stimulated by an increase in carbon dioxide?
A) irritant receptors
B) pressure receptors
C) osmoreceptors
D) peripheral chemoreceptors
E) baroreceptors.

c
Level: 2

84. When carbon dioxide levels in the blood increase, the
A) condition is called hypocapnia.
B) pH of the blood increases.
C) blood becomes more acidic.
D) number of hydrogen ions in the blood decreases.
E) blood becomes more alkaline.

d
Level: 2

85. After hyperventilating for several minutes, a person may develop short periods of apnea because
A) blood pH would drop and inhibit inspiration.
B) oxygen in the lungs has not had time to diffuse into the blood.
C) the level of oxygen has increased and inhibits the inspiratory center.
D) the level of CO2 decreases below the level necessary to stimulate the inspiratory center.
E) blood pH will rise and stimulate expiration.

c
Level: 2

86. Blood oxygen levels
A) are more important than carbon dioxide levels in the regulation of respiration.
B) need to change only slightly to cause a change in respiration rate.
C) within the normal PO2 range have little effect on regulation of respiration.
D) in venous blood and arterial blood are about the same.
E) never change enough to influence respiration.

b
Level: 1

87. The major regulator of respiration is the plasma concentration of
A) oxygen.
B) carbon dioxide.
C) water vapor.
D) nitrogen.
E) chloride.

b
Level: 1

88. The Hering-Breuer reflex
A) causes erratic respirations.
B) helps prevent overinflation of the lungs.
C) has its sensory components in the sympathetic nerves.
D) is a normal response to increased oxygen content in the blood.
E) limits how much air a person can expire.

d
Level: 2

89. During exercise, ventilation initially increases due to
A) increased blood carbon dioxide levels stimulating baroreceptors.
B) decreased blood oxygen levels stimulating chemoreceptors.
C) decreased blood pH levels stimulating baroreceptors.
D) limb movements that stimulate the respiratory center.
E) abrupt changes in metabolism or blood gases.

d
Level: 1

90. Which of the following is mismatched?
A) bronchitis - inflammation of the bronchi
B) emphysema - destruction of the alveolar walls
C) pulmonary fibrosis - loss of elastic recoil in the lung
D) cystic fibrosis - replacement of lung tissue with fibrous connective tissue
E) smokers - chronic obstructive pulmonary disease

c
Level: 1

91. A respiratory disease characterized by decreased chloride ion diffusion out of cells and dehydrated respiratory secretions is
A) bronchitis.
B) emphysema.
C) cystic fibrosis.
D) pulmonary fibrosis.
E) lung cancer.

d
Level: 3

92. A patient has severe pneumonia, which has thickened the respiratory membrane. Despite oxygen therapy, he still has rapid respirations and feels as if he is not getting enough air. This is because
A) the oxygen increases the stimulation of the carotid and aortic bodies.
B) the oxygen stimulates the respiratory center to increase the respiratory rate.
C) his blood pH increased and stimulated an increase in his respiratory rate.
D) even though he is receiving enough oxygen, carbon dioxide and hydrogen ions accumulate in his blood and cause the respiratory rate to continue to increase.
E) oxygen cannot diffuse across the thickened membrane.

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