Regulation of breathing is a complex and vital process that involves a network of neural and chemical mechanisms working in tandem to ensure optimal oxygen supply to tissues and efficient removal of carbon dioxide from the body.
Controlled primarily by the respiratory centers located in the brainstem, this physiological system balances multiple variables such as oxygen and carbon dioxide levels, pH, and metabolic demands.
Understanding the mechanisms behind the regulation of breathing is critical, not just for medical practitioners and researchers but also for individuals who engage in activities that test the limits of respiratory function.
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What is the Regulation of Breathing?
The regulation of breathing is a vital physiological process managed by the brainstem, which controls the diaphragm and intercostal muscles for inhalation and exhalation. Chemical sensors monitor blood levels of oxygen, carbon dioxide, and pH, triggering adjustments in breathing rate and depth to maintain homeostasis. Disruptions in this process can lead to serious health issues.
How is Breathing Controlled by the Body?
Breathing is primarily regulated by the brainstem, specifically in areas called the medulla oblongata and the pons.
Neurons in these regions send rhythmic signals to the muscles involved in breathing, primarily the diaphragm and the intercostal muscles (the muscles between your ribs), telling them when to contract and relax.
- Chemical Regulation: Specialized cells, known as chemoreceptors, continuously monitor the levels of oxygen, carbon dioxide, and pH in the blood. If they detect an imbalance—like too much CO2—the brainstem adjusts the rate and depth of breathing to correct it.
- Neural Regulation: Your body also uses afferent signals, feedback from other parts of the body like the stretch receptors in the lungs, to help fine-tune the breathing process. For example, if the lungs are overinflated, these receptors send a signal to the brain to halt inhalation, preventing potential damage.
- Higher Brain Functions: While the basic mechanisms of breathing are automatic, higher brain centers like the cerebral cortex can also influence them. For instance, you can voluntarily hold your breath or change your breathing pattern. However, when unconscious, like during sleep or under anesthesia, the automatic controls in the brainstem take full control.
- Environmental Factors: External factors such as altitude, pollutants, or even emotional states can also impact breathing and are integrated into the control systems.
Note: By understanding both the mechanical function of the lungs and the complex regulatory systems that govern breathing, we can better appreciate the intricate balance that keeps us alive and breathing every day.
What is the Central Role of the Brainstem?
The brainstem houses the medulla oblongata and the pons, two key areas responsible for involuntary breathing.
Neurons in these areas send impulses to the diaphragm and intercostal muscles, causing them to contract and initiate the process of inhalation and exhalation.
The rate and depth of breathing can be adjusted by these centers based on incoming information from sensory systems.
Chemoreceptors located in the brainstem and peripheral arteries continuously monitor the levels of oxygen, carbon dioxide, and the pH of the blood.
A rise in carbon dioxide levels or a drop in pH will trigger an increase in the breathing rate and depth to expel excess CO2 and correct the imbalance.
Conversely, low CO2 levels will slow down breathing. Oxygen levels generally have a less immediate impact on breathing rate, but extreme hypoxia can stimulate an increase in respiratory activity.
Voluntary Control and the Cerebral Cortex
While involuntary mechanisms dominate the regulation of breathing, the cerebral cortex can exert voluntary control, allowing us to hold our breath or alter our breathing pattern temporarily.
However, the body’s innate drive to maintain homeostasis usually overrides such voluntary actions if they pose a risk, forcing us to resume normal breathing.
Feedback Loops and Reflexes
Reflexes such as the Hering-Breuer inflation reflex prevent over-inflation of the lungs, serving as protective mechanisms.
Feedback loops, often mediated through hormones or other signaling molecules, can also influence breathing.
For example, during exercise, increased metabolic activity generates more CO2, and the body responds by increasing the rate and depth of breathing to match the elevated demand for oxygen and the need for CO2 removal.
Disruptions in the regulation of breathing can result from a variety of causes, including neurological disorders, respiratory diseases like COPD and asthma, and metabolic imbalances.
Understanding the intricate systems regulating breathing can inform treatment strategies for these conditions, as well as interventions for acute situations like hypoxia or hypercapnia.
Practice Questions About the Regulation of Breathing
1. What is apnea?
The absence of spontaneous breathing.
2. What is the apneustic center?
An anatomically ill-defined, localized collection of neurons in the pons located at the level of the vestibular area that moderates the rhythmic activity of the medullary respiratory centers.
3. What is Biot respirations?
An abnormal breathing pattern characterized by irregular periods of apnea alternating with periods in which 4 or 5 breaths of identical depth are taken.
4. What are chemoreceptors?
Sensory nerve cells activated by changes in the chemical environment surrounding it.
5. What is Cheyne-Stokes respiration?
An abnormal breathing pattern where the respiratory rate and tidal volume gradually increase and then gradually decrease to complete apnea.
6. What is the Hering-Breuer inflation reflex?
The parasympathetic inflation reflex mediated via the lungs stretch receptors that appears to influence the duration of the expiratory pause occurring between breaths.
7. What is the pneumotaxic center?
A bilateral group of neurons in the upper part of the pons that rhythmically inhibits inspiration.
8. What are vagovagal reflexes?
Reflexes caused by stimulation of parasympathetic receptors in the airways that can result in laryngospasm, bronchoconstriction, hyperpnea, and bradycardia.
9. What stimulates the vagovagal reflexes?
They are often associated with mechanical stimulation, as during procedures such as tracheobronchial aspiration, intubation, or bronchoscopy.
10. Is breathing a conscious or automatic activity?
11. Can breathing patterns be consciously changed?
Yes; until willful breathing stops and the neural mechanisms resume.
12. Where does the rhythmic cycle of breathing originate?
It originates in the brain stem, specifically the neurons in the medulla.
13. Do separate inspiratory and expiratory centers exist?
No; the neurons are anatomically intermingled and do not inhibit one another.
14. The medulla contains several widely dispersed respiratory-related what?
15. Which respiratory group contains mainly inspiratory neurons?
16. Which respiratory group contains both inspiratory and expiratory neurons?
17. What does DRG stand for?
Dorsal respiratory group
18. What does VRG stand for?
Ventral respiratory group
19. What are the characteristics of DRG?
They are bilateral in the medulla; they send impulses to motor nerves of the diaphragm and intercostals; and they provide the main inspiratory stimulus.
20. What modifies the medulla’s basic breathing pattern?
Sensory impulses that the lungs, airways, peripheral chemoreceptors, and joint proprioceptors have transmitted to the DRG.
21. Do DRG nerves extend into VRG nerves?
Yes, many of them do.
22. Do VRG nerves extend into DRG nerves?
Only a few.
23. What are the characteristics of the VRG?
They are bilateral in the medulla; they send motor impulses through the vagus nerve to increase the diameter of the glottis, transmitting impulses to the diaphragm and intercostals; and they send expiratory impulses to the internal intercostals and abdominals.
24. What is the principle of the pacemaker hypothesis?
Medullary cells have intrinsic pacemaker properties that drive other medullary neurons.
25. What is the principle of the network hypothesis?
That rhythmic breathing is the result of a particular pattern of interconnections between neurons dispersed throughout the VRG, the pre-Botzinger complex, and the Botzinger complex; inspiratory and expiratory neurons inhibit one another.
26. Does spontaneous respiration continue if the brain stem is transected above the medulla?
Yes, though it is irregular.
27. Does the pons promote rhythmic breathing?
No; it modifies the output of the medullary centers.
28. What are the two respiratory centers of the pons?
Apneustic and pneumotaxic
29. What happens when the apneustic center gets severed from the pneumotaxic center and vagus nerve?
DRG neurons fail to switch off, causing prolonged inspiratory gasps interrupted by occasional expirations; i.e., apneustic breathing.
30. What do strong pneumotaxic signals do?
They increase the respiratory rate.
31. What do weak pneumotaxic impulses do?
They prolong inspiration and increase tidal volume.
32. The apneustic and pneumotaxic centers seem to work together to control what?
The depth of inspiration.
33. Where are the Hering-Breuer inflation reflex receptors located?
In the smooth muscle of both the large and small airways.
34. Which nerve carries the inhibitory impulses from the Hering-Breuer reflex receptors to the DRG?
The vagus nerve
35. Is the Hering-Breuer inflation reflex an important control mechanism in quiet breathing?
No, this reflex is only activated at large tidal volumes (in adults).
36. Why is the Hering-Breuer inflation reflex important?
It regulates rate and depth during moderate to strenuous exercise.
37. Rapidly adapting irritant receptors in the epithelium of the larger conducting airways have what?
Vagal sensory nerve fibers.
38. Stimulation of irritant receptors can cause what?
Reflex bronchoconstriction, coughing, sneezing, tachypnea, and narrowing of the glottis.
39. What can stimulate vagovagal reflexes?
Endotracheal intubation, airway suctioning, and bronchoscopy.
40. Airway suctioning and bronchoscopy can cause what?
Severe bronchoconstriction, coughing, and laryngospasm.
41. What is the main trigger of chemoreceptors?
H+ (indirectly CO2)
42. Where are the central chemoreceptors located?
Bilaterally in the medulla
43. Are the central chemoreceptors in direct contact with arterial blood?
No, they are bathed in CSF and separated by the blood-brain barrier.
44. What is the blood-brain barrier?
A semipermeable membrane that separates the cerebrospinal fluid (CSF) and the blood.
45. How does CO2 affect the central chemoreceptors?
Arterial CO2 easily diffuses across the blood-brain barrier, and once inside, it reacts with H2O; Carbonic anhydrase follows, resulting in H+ and HCO3, and the central chemoreceptors are extremely sensitive to H+.
46. Can H+ pass through the blood-brain barrier?
Rarely, it is almost impermeable to H+ and HCO3, so CO2 has to pass through and then react with water once it’s inside.
47. CO2 diffusing from the blood into the CSH increases H+ almost instantly, exciting what?
48. How long does central chemoreceptor stimulation usually last while in respiratory acidosis?
1-2 days, which is long enough for the kidneys to raise levels of HCO3 in the blood and enough can pass the blood-brain barrier to buffer the H+.
49. Where are the peripheral chemoreceptors located?
The aortic arch and bilaterally in the bifurcations of the common carotid arteries.
50. The peripheral chemoreceptors increase their firing rates in response to what?
Increased arterial H+ regardless of origin.
51. Which nerve carries impulses from the carotid chemoreceptors to the medulla?
52. Which nerve carries impulses from the aortic chemoreceptors to the medulla?
53. Which peripheral chemoreceptors have more influence over the respiratory center?
Carotid, due to an extremely high rate of blood flow, little time to deposit O2, and exposure to arterial blood 100% of the time.
54. How does hypoxemia affect the peripheral chemoreceptors?
Low O2 makes them more sensitive to H+.
55. Why does a decreased PaO2 cause increase ventilation?
Because it makes the carotid chemoreceptors more sensitive to H+, which causes them to fire more frequently.
56. How does an increased PaO2 affect the peripheral chemoreceptors?
It makes them less sensitive to H+.
57. Why does an increased PaO2 cause a decrease in ventilation?
The carotid chemoreceptors become less sensitive to H+, which causes them to fire less often.
58. When does hypoxemia not have an effect on the carotid chemoreceptors?
Severe alkalemia because, even though the carotid chemoreceptors are more sensitive to H+, there is a lot less in blood at that time.
59. The carotid bodies meet their O2 needs from what?
From dissolved O2 because the flow rate is so fast; therefore, it depends less on content and more on partial pressure.
60. When will the nerve-impulse transmissions of the carotid bodies increase when pH and PaCO2 are normal?
When PaO2 decreases to approximately 60 mmHg.
61. What accounts for the sharpest decrease in O2 content on the O2-Hb equilibrium curve?
A decrease in PaO2 from 60 mmHg to 30 mmHg.
62. What percentage do the peripheral chemoreceptors account for in the ventilatory response to hypercapnia?
63. Which responds more rapidly to increased H+?
64. When peripheral chemoreceptors become insensitive to H+ levels because of a high PaO2, what does the ventilatory response depend on?
It depends on the central chemoreceptors, which are unaffected by hypoxemia.
65. Does a diagnosis of COPD on a patient’s chart automatically mean high PaCO2 or that O2 administration may be associated with hypercapnia?
No, these characteristics are only displayed in severe end-stage disease.
66. Should O2 be withheld from acutely hypoxemic patients with COPD?
No, the fear of hypoventilation and/or hypercapnia does not override oxygenating the tissues.
67. What should you be prepared to do if O2 administration is accompanied by severe hypoventilation?
Provide mechanical ventilatory support
68. Which breathing pattern occurs when cardiac output is low, as in congestive heart failure, or brain injuries?
69. Why does decreased cardiac output cause Cheyne-Stokes breathing?
Because there is a delay in blood transit time between the lungs and the brain.
70. What causes Biot’s respiration?
Increased intracranial pressure
71. What can apneustic breathing indicate?
Damage to the pons.
72. Central neurologic hyperventilation is characterized by what?
Persistent hyperventilation driven by abnormal neural stimuli; related to mid-brain and upper pons damage associated with head trauma, severe brain hypoxia, or lack of blood flow to the brain.
73. What are the characteristics of central neurogenic hypoventilation?
Unresponsive to ventilatory stimuli; associated with head trauma, brain hypoxia, and narcotic suppression of the respiratory center.
72. CO2 plays an important role in what?
Cerebral blood flow
73. How does high CO2 affect cerebral blood flow?
It dilates the cerebral vessels increasing blood flow.
74. How does low CO2 affect cerebral blood flow?
It constricts cerebral vessels decreasing blood flow.
75. Why is high intracranial pressure bad?
If it exceeds cerebral arterial pressure, blood flow to the brain will stop, leading to cerebral hypoxia (ischemia).
76. Why does decreasing PaCO2 help relieve ICP?
For every 1 mmHg reduction in PaCO2, there is a 3% reduction in cerebral blood flow. For every 0.5-0.7 drop in cerebral blood flow, there is a 1 mmHg reduction in ICP.
77. Why is mechanical hyperventilation a cause for concern for patients with traumatic brain injuries?
Because with the drop in ICP also comes a drop in cerebral blood flow, which can end up causing ischemia.
78. What is the normal ICP?
79. What is the most common cause of hypoxemia?
80. Apneustic breathing indicates damage to what?
81. Central neurogenic hyperventilation is characterized by what?
It is characterized by persistent hyperventilation driven by abnormal neural stimuli.
82. When does neurogenic hyperventilation occur?
It occurs with midbrain and upper pons damage associated with head trauma, severe brain hypoxia, or lack of blood flow to the brain.
83. What is central neurogenic hypoventilation?
When the respiratory centers do not respond appropriately to ventilatory stimuli.
84. What are the two predominant theories of rhythm generation?
Pacemaker hypothesis and network hypothesis
85. What is the pacemaker hypothesis?
Certain medullary cells have intrinsic pacemaker properties, and these cells drive other medullary neurons.
86. What is the network hypothesis?
Rhythmic breathing is the result of a particular pattern of interconnections between neurons dispersed throughout the rostral VRG, pre-Botzinger complex, and Botzinger complex. Inspiratory and expiratory neurons inhibit one another.
87. The firing rate of DRG and VRG inspiratory neurons increases gradually at the end of what phase?
The expiratory phase
88. During quiet breathing, inspiratory neurons fire with increasing frequency for approximately how many seconds?
89. After the 2-second firing, an abrupt switch-off occurs, allowing expiration to proceed for how many seconds?
90. The inhibitory neurons that switch off the inspiratory ramp signal are controlled by what?
The pneumotaxic center and pulmonary stretch receptors
91. The pons does not promote rhythmic breathing but rather?
It modifies the output of the medullary centers.
92. Strong pneumotaxic signals increase what?
93. What reflexes have both sensory and motor vagal components?
94. What reflexes are responsible for laryngospasm, coughing, and slowing of the heartbeat?
95. Endotracheal intubation, airway suctioning, and bronchoscopy readily elicit what reflex?
96. What are proprioceptors?
They send stimulatory signals to the medullary respiratory center, increase medullary inspiratory activity, and cause hyperpnea.
97. The body maintains the proper amounts of oxygen, carbon dioxide, and hydrogen ions in the blood mainly by regulating what?
98. Chemoreceptors transmit impulses to the medulla, which will increase what?
99. Why does the stimulatory effect of chronically high CO2 on the central chemoreceptors gradually decline over one or two days?
Because the kidneys retain bicarbonate ions in response to respiratory acidosis, bringing the blood pH level back to normal.
100. The peripheral chemoreceptors are?
Small, highly vascular structures known as the carotid and aortic bodies.
101. Peripheral chemoreceptors fire more frequently in the presence of what?
Arterial hypoxemia, because hypoxemia makes them more sensitive to hydrogen.
102. When pH and PaCO2 are normal, the carotid bodies’ nerve-impulse transmission rate does not increase significantly until the PaO2 decreases to what?
About 60 mmHg
103. Arterial hypoxemia does not stimulate ventilation greatly until the PaO2 decreases below what?
104. Hypoxia-induced hyperventilation lowers what?
105. People with chronic hypercapnia secondary to advanced COPD have depressed ventilatory responses to acute rises in what?
106. The ventilatory response to hypoxemia is greatly enhanced by what?
Hypercapnia and acidemia
107. A sudden rise in arterial PaCO2 causes an immediate increase in what?
Ventilation, because CO2 rapidly diffuses from the blood into the CSF, increasing the [H+] surrounding the central chemoreceptors.
108. When does the Cheyne-Stokes respiration pattern occur?
This pattern occurs when cardiac output is low, as in congestive heart failure, delaying the blood transit time between the lungs and the brain, including injuries in which the respiratory centers over-respond to changes in the PCO2 level.
109. What is Biot’s respiration?
It is similar to Cheyne-Stokes respiration, except the tidal volumes are of identical depth.
110. When does the Biot’s respiratory pattern occur?
It occurs in patients with increased intracranial pressure.
The regulation of breathing is an essential physiological process involving neural circuits, chemical sensors, and feedback loops.
This system ensures that the body’s oxygen and carbon dioxide levels are maintained within narrow physiological limits, adapting to various internal and external challenges.
Disruptions to this regulatory framework can result in medical conditions that necessitate prompt diagnosis and intervention.
Therefore, advancing our understanding of the mechanisms involved in breathing regulation has significant implications for healthcare, athletics, and general well-being.
John Landry is a registered respiratory therapist from Memphis, TN, and has a bachelor's degree in kinesiology. He enjoys using evidence-based research to help others breathe easier and live a healthier life.
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