Control of Respiration

Graphics are used with permission of:

Pearson Education Inc., publishing as Benjamin Cummings (http://www.aw-bc.com)

Page 1. Introduction
• The basic rhythm of breathing is controlled by respiratory centers located in the
brainstem.
• This rhythm is modified in response to input from sensory receptors and from other
regions of the brain.

Page 2. Goals
• To understand how the respiratory centers control breathing to maintain
homeostasis.
• To examine how PCO2, pH, PO2, and other factors affect ventilation.
• To understand the relationship between breathing and blood pH.
• To explore the factors which stimulate increased ventilation during exercise.

Page 3. Homeostasis and the Control of Respiration

 • Fill out the chart to the right as you
proceed through this page.
• The control of respiration is tied to the
principle of homeostasis.
• Recall that the body maintains
homeostasis through homeostatic
control mechanisms, which have
three basic components:
1. receptors
2. control centers
3. effectors
• The principal factors which control
respiration are chemical factors in
the blood.
• Changes in arterial PCO2, PO2 and
pH are monitored by sensory
receptors called chemoreceptors.
• The chemoreceptors send sensory
input to respiratory centers in the
brainstem, which determine the
appropriate response to the
changing variables.
• These centers then send nerve
impulses to the effectors, the
respiratory muscles, to control the
force and frequency of contraction.
• This changes the ventilation, the rate
and depth of breathing.
• Ventilation changes restore the
arterial blood gases and pH to their
normal range.

Page 4. Inspiratory Neurons

• Label the diagram to the right.
• The basic rhythm of breathing
is controlled by respiratory
centers located in the
medulla and pons of the
brainstem.
• Within the medulla, a group of
neurons in the ventral
respiratory group sets the
basic rhythm by
automatically initiating
inspiration.

• The inspiratory neurons sends nerve impulses along the phrenic nerve to the
diaphragm and along the intercostal nerves to the external intercostal muscles.
• The nerve impulses to the diaphragm and the external intercostal muscles continue
for a period of about 2 seconds. This stimulates the inspiratory muscles to
contract, initiating inspiration.
• A second group of neurons In the ventral respiratory group now fires, inhibiting the
inspiratory neurons for about 3 seconds, which allows the muscles to relax. The
elastic recoil of the lungs and chest wall leads to expiration.
• The automatic rhythm generated by these two groups of neurons alternately
inhibiting each other produces the normal resting breathing rate, ranging between
12 and 15 breaths per minute.
• Label this diagram:
Page 5. Other Respiratory Control Centers
• The dorsal respiratory group, or DRG, acts as an integrating center for peripheral
stretch and chemoreceptor inputs, and influences the activity of the neurons in
the VRG.
• Both the DRG and the VRG receive inputs from other respiratory centers in the
pons, which modify inspiration, and allow for smooth transitions between
inspiration and expiration.
• Label the diagram on the next page.
 ** Now is a good time to go to quiz question 1:
• Click the Quiz button on the left side of the screen.
• After answering question 1, click the Back to Topic button on the left side of the screen.
• To get back to where you left off, click on the scrolling page list at the top of the screen and choose "6.
Location of the Chemoreceptors".

Page 6. Location of the Chemoreceptors

• Although the basic rhythm of breathing is established by the respiratory centers, it
is modified by input from the central and peripheral chemoreceptors.
• They respond to changes in the PCO2, pH, and PO2 of arterial blood, which are the
most important factors that alter ventilation.

• The central chemoreceptors in the medulla monitor the pH associated with CO2 levels
within the brain. The chemoreceptors synapse directly with the respiratory centers.
• The peripheral chemoreceptors are found in two locations:
1. the aortic bodies within the aortic arch
2. the carotid bodies at the bifurcation of the common carotid arteries
 • The peripheral chemoreceptors monitor the PCO2, pH and PO2 of arterial blood.
This information travels to the respiratory centers via the vagus and
glossopharyngeal nerves.

Page 7. Central Chemoreceptors: Effect of PCO2

 • The most important factor controlling the rate and depth of breathing is the effect of
carbon dioxide on the central chemoreceptors.
• Carbon dioxide readily diffuses from the blood into the brain. Here, carbon dioxide
combines with water to form carbonic acid, which dissociates into hydrogen ions
and bicarbonate ions.
• The hydrogen ions stimulate the central chemoreceptors, which send nerve
impulses to the respiratory centers in the medulla.
• As carbon dioxide increases, so does the number of hydrogen ions, which in turn
lowers the pH. The central chemoreceptors actually respond to this pH change
caused by the blood PCO2.

Page 8. Predict the Effect of Increased PCO2

 • Fill in the diagram to the right:
• What will happen to the breathing
rate and depth if the arterial PCO2
increases?
• An increase in the PCO2 in the blood
leads to an increase in hydrogen
ions in the brain, decreasing the pH.
• The central chemoreceptors fire more
frequently, sending more nerve
impulses to the respiratory centers,
which in turn send more nerve
impulses to the respiratory muscles.
• This results in an increased breathing
rate and depth, allowing more
carbon dioxide to be exhaled,
returning the blood PCO2 to normal
levels.

** Now is a good time to go to quiz question 2:

• Click the Quiz button on the left side of the screen.
• Click on the scrolling page list at the top of the screen and choose "2: Central Chemoreceptors".
• After answering question 2, click the Back to Topic button on the left side of the screen.
• To get back to where you left off, click on the scrolling page list at the top of the screen and choose "9.
Peripheral Chemoreceptors: Effect of pH Changes".

Page 9. Peripheral Chemoreceptors: Effect of pH Changes

• The peripheral chemoreceptors also respond to pH changes caused by PCO2
changes, however they directly monitor changes in the arterial blood, not the
cerebrospinal fluid as the central chemoreceptors do.
• The role of the peripheral chemoreceptors:
• Increased carbon dioxide levels in the arterial blood result in decreased blood
pH, which stimulates the peripheral chemoreceptors.
• They respond by sending more nerve impulses to the respiratory centers, which
stimulate the respiratory muscles, causing faster and deeper breathing.
• More carbon dioxide is exhaled, which drives the chemical reaction to the left
and returns the PCO2 and pH to normal levels.
 • Fill in the diagram to the right:
• The peripheral chemoreceptors
also respond to acids such as
lactic acid, which is produced
during strenuous exercise:
• Active muscles produce lactic
acid, which enters the blood,
releases hydrogen ions, and
lowers the pH.
• The decreased pH stimulates
the peripheral
chemoreceptors to send more
nerve impulses to the
respiratory centers, which
stimulate the respiratory
muscles to increase the
breathing rate and depth.
• More carbon dioxide is
exhaled, lowering the PCO2
in blood, driving the chemical
reaction to the left, and
lowering hydrogen ion levels.

Page 10. Peripheral Chemoreceptors: Effect of PO2

• The peripheral chemoreceptors
also monitor arterial PO2,
however, the arterial PO2 must
drop below 60 millimeters of
mercury before the
chemoreceptors respond.
• The normal alveolar PO2 of
about 100 millimeters of
mercury results in 98%
hemoglobin saturation in the
blood.
• If the PO2 drops to 60
millimeters of mercury,
hemoglobin is still 90%
saturated.
• Any increased ventilation in this
range of PO2's results in only
a small increase in the amount
of oxygen loaded into the
blood.
• However, at very high altitudes,
the alveolar PO2 may fall to 40
millimeters of mercury and
hemoglobin will be only 75%
saturated. At this point,
increased ventilation will make
a dramatic difference in the
amount of oxygen loaded into
the blood.
 • The low PO2 in the blood stimulates
the peripheral chemoreceptors to
send nerve impulses to the
respiratory centers which stimulate
the respiratory muscles, increasing
ventilation. More oxygen is inhaled,
and the arterial PO2 returns to
normal levels.

** Now is a good time to go to quiz questions 3 and 4:

• Click the Quiz button on the left side of the
screen.
• Click on the scrolling page list at the top of the
screen and choose "3. Peripheral
Chemoreceptors: O2".
• After answering question 4b, click the Back to
Topic button on the left side of the screen.
• To get back to where you left off, click on the
scrolling page list at the top of the screen
and choose "11. Hyperventilation".

Page 11. Hyperventilation

 • What changes will occur if a
person hyperventilates, that
is, breathes deeper and
faster than necessary for
normal gas exchange?
• During hyperventilation,
carbon dioxide is exhaled,
lowering the PCO2.
• This drives the chemical
reaction to the left,
decreasing the hydrogen ion
concentration, and
increasing pH:
CO2 + H2O H2CO3 H+ +
HCO3-

• Since the PCO2 is low, the

central chemoreceptors
send fewer impulses to the
respiratory centers.
• Since the pH is high, the
peripheral chemoreceptors
also send fewer impulses to
the respiratory centers,
which send fewer nerve
impulses to the respiratory
muscles, thereby further
decreasing breathing rate
and depth and returning
the arterial gases and pH to
normal levels.

• Hyperventilation does not normally cause an increase in the oxygen levels in the
blood, because oxygen is poorly soluble in blood and normally hemoglobin in
arterial blood is saturated with oxygen already.

Page 12. Hypoventilation

 • Now predict what changes will
occur if a person
hypoventilates.
• Hypoventilation occurs when
the breathing rate and depth
is too low to maintain normal
blood gas levels.
• During hypoventilation, not
enough oxygen is inhaled, so
the PO2 decreases. In
addition, carbon dioxide
builds up in the blood,
increasing the PCO2. This
drives the chemical reaction
to the right, increasing the
H+ concentration and
decreasing pH.
• The PO2 drops, but not
enough to stimulate the
peripheral chemoreceptors.
• The high PCO2 stimulates the
central chemoreceptors to
send more impulses to the
respiratory centers.
• A decrease in pH stimulates
the peripheral
chemoreceptors, which also
send more nerve impulses to
the respiratory centers, which
stimulate the respiratory
muscles, increasing the
breathing rate and depth.
• This allows oxygen to be
inhaled, carbon dioxide to be
exhaled, and drives the
chemical reaction to the left,
returning the arterial gases
and pH to normal levels.

Page 13. Summary: Effects of PO2, pH, and PCO2

• This chart summarizes how the three major chemical factors - PO2, pH, and PCO2 -
modify breathing rate and depth.
• When the PO2 drops below 60 millimeters of mercury, the peripheral
chemoreceptors send nerve impulses to the respiratory centers. The respiratory
 centers send nerve impulses to the respiratory muscles, increasing ventilation.
More oxygen is inhaled, returning the PO2 to normal levels.
• When cells release acids into the blood, the acids release hydrogen ions, which
lower the pH. This stimulates the peripheral chemoreceptors to send more nerve
impulses to the respiratory centers. They, in turn, send more nerve impulses to
the respiratory muscles, increasing ventilation. More carbon dioxide is exhaled,
which returns the pH to normal levels.
• An increase in PCO2 leads to a decreased pH in the blood, which stimulates the
peripheral chemoreceptors to send more nerve impulses to the respiratory centers.
In addition, the increased PCO2 leads to a decreased pH within the brain. This
stimulates the central chemoreceptors to send more nerve impulses to the
respiratory centers. The respiratory centers send more nerve impulses to the
respiratory muscles, which increase breathing rate and depth. More carbon
dioxide is exhaled, returning the PCO2 and pH to normal levels.

Page 14. Other Factors Which Influence Ventilation

Several other factors influence ventilation. These factors include:
1. Voluntary control.
• By sending signals from the cerebral cortex to the respiratory muscles, we
can voluntarily change our breathing rate and depth when holding our
breath, speaking, or singing.
 • However, chemoreceptor input to the respiratory centers will eventually
override conscious control and force you to breathe.
2. Pain and emotions.
• Pain and strong emotions, such as fear and anxiety, act by way of the
hypothalamus to stimulate or inhibit the respiratory centers.
• Laughing and crying also significantly alter ventilation.
3. Pulmonary irritants.
• Dust, smoke, noxious fumes, excess mucus and other irritants stimulate
receptors in the airways.
• This initiates protective reflexes, such as coughing and sneezing, which
forcibly remove the irritants from the airway.
4. Lung hyperinflation.
• Stretch receptors in the visceral pleura and large airways send inhibitory
signals to the inspiratory neurons during very deep inspirations, protecting
against excessive stretching of the lungs. This is known as the inflation, or
Hering-Breuer, reflex.

Page 15. Exercise and Ventilation

• Changes in ventilation during exercise:
• Ventilation increases during strenuous exercise, with the depth increasing more
than the rate.
• It appears that changes in PCO2 and PO2 do not play a significant role in
stimulating this increased ventilation.
• Although the precise factors which stimulate increased ventilation during exercise
are not fully understood, they probably include:
1. Learned responses.
• Ventilation increases within seconds of the beginning of exercise, probably in
anticipation of exercise, a learned response.
2. Neural input from the motor cortex.
• The motor areas of the cerebral cortex which stimulate the muscles also
stimulate the respiratory centers.
3. Receptors in muscles and joints.
Proprioceptors in moving muscles and joints stimulate the respiratory centers.
4. Increased body temperature.
• An increase in body temperature stimulates the respiratory centers.
5. Circulating epinephrine and norepinephrine.
• Circulating epinephrine and norepinephrine secreted by the adrenal medulla
stimulates the respiratory centers.
6. pH changes due to lactic acid
• Lactic acid, produced by exercising muscles, is another stimulus.

Page 16. Summary

• The basic rhythm of breathing is set by the ventral respiratory group, located in the
medulla. Other respiratory centers, located in the medulla and pons, also control
breathing.
• Chemoreceptors monitor the PCO2, pH, and PO2 of arterial blood and alter the
basic rhythm of breathing.
 • Carbon dioxide, reflected by changes in pH, is the most important stimulus
controlling ventilation.
• pH changes due to metabolic acids also alter ventilation.
• Oxygen stimulates ventilation only when the blood PO2 is very low.
• Other factors, such as voluntary control, pain and emotions, pulmonary irritants,
and lung hyperinflation, also play roles in controlling ventilation.
• The control of ventilation during exercise, while complex and not fully understood,
involves multiple inputs including chemical and neural factors.

** Now is a good time to go to quiz questions 5 and 6:

• Click the Quiz button on the left side of the screen.
• Click on the scrolling page list at the top of the screen and choose "5.Change in Breathing Rate and Depth".
• Work through quiz questions 5 and 6.

Notes on Quiz Questions:

Quiz Question #1a,b: Respiratory Centers
• This question asks you to identify the parts of the brain which are responsible for
setting the basic rhythm of breathing, forceful expiration, and allowing for smooth
transitions between inspiration and expiration.

Quiz Question #2a,b: Central Chemoreceptors

• This question asks you to chose the substances that stimulates the central
chemoreceptors.

Quiz Question #3: Peripheral Chemoreceptors: CO2

• This question asks you to list the sequence of events that occurs when there is an
increase in blood levels of carbon dioxide.

Quiz Question #4a,b: Peripheral Chemoreceptors: O2

• This question asks you to predict when peripheral chemoreceptors will be
stimulated due to lack of oxygen and how they respond

Quiz Question #5: Change in Breathing Rate and Depth

• This question asks you to determine the factors that will increase the rate of
respiration.

Quiz Question #6a,b: Breath Holding

• This question asks you to predict what happens when you hold your breath.

Study Questions on Control of Respiration:

1. (Page 1.) What controls the basic rhythm of breathing?

2. (Page 3.) What are the three components of a homeostatic control mechanisms?

3. (Page 3.) What are the principal factors which control respiration?

4. (Page 3.) What monitors changes in arterial PCO2, PO2 and pH?
5. (Page 3.) Where do the chemoreceptors send sensory input to?

6. (Page 3.) Where do the respiratory centers send impulses to?

7. (Page 3.) How is homeostasis of PCO2, PO2 and pH maintained?

8. (Page 4.) Label the first diagram on p. 4.

9. (Page 4.) Where, within the brainstem, is the respiratory center that controls the basic
rhythm of breathing?

10. (Page 4.) Where, within the brainstem, are the inspiratory neurons?

11. (Page 4.) Label the anatomy on the second diagram on p. 4.

12. (Page 4.) Explain how the inspiratory neurons initiate inspiration.

13. (Page 4.) Explain how the inspiratory neurons initiate expiration.

14. (Page 4.) What is a normal respiratory rate?

15. (Page 5.) Label the diagram on page 5.

16. (Page 5.) What is the function of the dorsal respiratory group?

17. (Page 5.) Where are the respiratory centers that are responsible for smooth
transitions between inspiration and expiration?

18. (Page 6.) Label the first diagram on page 6.

19. (Page 6.) Label the second diagram on page 6.

20. (Page 6.) What are the two general categories of chemoreceptors involved in
respiration?

21. (Page 6.) Where are the central chemoreceptors located?

22. (Page 6.) Where are the peripheral chemoreceptors located?

23. (Page 6.) What do the central chemoreceptors monitor?

24. (Page 6.) What do the peripheral chemoreceptors monitor?

25. (Page 6.) How does information get from the chemoreceptors to the respiratory
centers?
26. (Page 7.) What is the most important factor controlling the rate and depth of
breathing?

27. (Page 7.) Does the carbon dioxide stimulate the central chemoreceptors directly?

28. (Page 7.) What is the relationship between hydrogen ions and pH?

29. (Page 7.) Label the diagram on page 7.

30. (Page 8.) In each of these blanks, put "increase(s)" or "decrease(s)": If the arterial
PCO2 increases, there is a(an) a. _______ in the PCO2 in the fourth ventricle. This
causes a(an) b. ________ in hydrogen ions in the cerebrospinal fluid, which c.
___________ the pH of the cerebrospinal fluid. The hydrogen ions stimulate the
central chemoreceptors to d. ________ their rate of firing, which e. __________ the
nerve impulses to the respiratory centers. This f. _______ the rate of nerve impulses
to the respiratory muscles, resulting in a(an) g. ______ in breathing rate and depth.
As a result, there is a(an) h. _________ in carbon dioxide exhalation which i. _________
the blood PCO2 to normal levels.

31. (Page 9.) Do peripheral chemoreceptors directly respond to changes in the arterial
blood, venous blood, or brain?

32. (Page 9.) What do the peripheral chemoreceptors directly respond to?
33. (Page 9.) In each of these blanks, put "increase(s)" or "decrease(s)": An increase in
carbon dioxide levels in the arterial blood result in a(an) a. _______ in blood pH.
There is a(an) b. ________ in the rate of firing of the peripheral chemoreceptors,
which c, _______ the rate of respiration. As a result there is a(an) d. ______ in carbon
dioxide exhalation, which drives the chemical reaction to the left and e. _________
PCO2 and pH returns to normal levels.

34. (Page 9.) In each of these blanks, put "increase(s)" or "decrease(s)": The peripheral
chemoreceptors also respond to acids such as lactic acid, which a. ________ during
strenuous exercise. The lactic acid enters the blood and b. __________ the
concentration of hydrogen ions which c. _________ the pH which d. _______ the
firing rate of the peripheral chemoreceptors. There is a(an) e. ________ in nerve
impulses to the respiratory centers, which f. _______ the breathing rate and depth.
There is a(an) g. _________ in carbon dioxide is exhalation which h. __________ the
PCO2 in blood, driving the chemical reaction to the left, and i. ________ hydrogen ion
levels.

35. (Page 10.) When are peripheral chemoreceptors stimulated by oxygen?

36. (Page 10.) In each of these blanks, put "increase(s)" or "decrease(s)": When the PO2
of the arterial blood decreases to below 60 mm Hg, there is a(an) a. _______ in the
rate of firing in the peripheral chemoreceptors resulting in a(an) b. _________ in nerve
impulses to the respiratory centers. As a result there is a(an) c. _________ in
 ventilation. As a result, the oxygen level in the blood d. _______ and the arterial PO2
returns to normal levels.

37. (Page 11.) In hyperventilation, which blood gas is affected the most, oxygen or
carbon dioxide?

38. (Page 11.) What happens to blood levels of carbon dioxide during hyperventilation?

39. (Page 11.) As a result of hyperventilation, which direction does this reaction go?
a. CO2 + H2O H2CO3 H+ + HCO3- b. CO2 + H2O H2CO3 H+ +
HCO3-

40. (Page 11.) In each of these blanks, put "increase(s)" or "decrease(s)": During
hyperventilation, carbon dioxide levels in the blood a. ________. This causes a(an) b.
______ in the hydrogen ion concentration. pH c. _________. The rate of firing of the
peripheral and central chemoreceptors d. __________. There is a(an) e. ________ in
impulses to the respiratory centers and the respiratory rate f. ________.

41. (Page 12.) What happens to blood levels of carbon dioxide during hypoventilation?

42. (Page 12.) As a result of hypoventilation, which direction does this reaction go?
a. CO2 + H2O H2CO3 H+ + HCO3- b. CO2 + H2O H2CO3 H+ +
HCO3-

43. (Page 12.) In each of these blanks, put "increase(s)" or "decrease(s)": During
hypoventilation, carbon dioxide levels in the blood a. ________. This causes a(an) b.
______ in the hydrogen ion concentration. pH c. _________. The rate of firing of the
peripheral and central chemoreceptors d. __________. There is a(an) e. ________ in
impulses to the respiratory centers and the respiratory rate f. ________.
44. (Page 14.) Besides pH, PCO2 and PO2what other factors influence ventilation?
45. (Page 14.) What is the Hering-Breuer reflex?
46. (Page 15.) Do changes in PCO2 and PO2 play a significant role in stimulating
increased ventilation due to exercise?
47. (Page 15.) What are the factors that stimulate increased ventilation during exercise?