rate and depth of breathing are regulated so that PaCO2 is maintained close to 40 mm Hg.
We can use the assumption that PaCO2 = PACO2 (i.e. that arterial CO2 is equivalent to alveolar CO2 concentrations). When PACO2 is regulated, PAO2 is automatically set to an appropriate value that depends on the ambient partial pressure of oxygen and the health of the lungs (V/Q distribution). The PaCO2 sensitive mechanism is the main controller of breathing. However, the PaCO2 controller can be overridden in systemic arterial hypoxemia (e.g., acclimatization to living at high altitude) by a PAO2 sensitive controller. This happens when arterial oxygen tension decreases below 60 mm Hg.
, chiefly stretch receptors in the walls of the airways, set the breathing frequency. They are stimulated by lung inflation and deflation. Stretch receptor input (afferent impulses via vagus) mainly influences inspiration. Interruption of the stretch receptors by cutting or cooling the vagus nerves prolongs inspiration.
Central and Peripheral chemoreceptors also play a role in control of breathing.
Both respond to changes in the CO2 and H+ concentrations. Elevation of PaCO2 up to 100 mm Hg cause a linear increase in ventilation. Also, at any level of PaCO2, ventilation is greater when acidosis prevails and less when alkalosis prevails. It is also important to note that the central chemoreceptors contribute ~75% of the total ventilatory response to CO2.
Although CO2 is the main controlled variable in breathing, when PaO2 decreases sufficiently, O2 sensors in the carotid body (peripheral chemoreceptors) are stimulated and ventilation increases. Interestingly, asphyxia (hypercapnia plus hypoxia) stimulates the drive to breath much more than does hypoxia alone. Hypercapnia enhances the ventilatory response to hypoxia, and inversely, hypoxia enhances the ventilatory response to hypercapnia.
Central Organization of Breathing
both the rate and depth of breathing are regulated so that PaCO2 is maintained close to 40mmHg
the PaCO2-sensitive mechanism is the main controller of breathing but can be overridden in systemic arterial hypoxemia by a PAO2-sensitive controller (when PAO2 < 60mmHg)
Types of Control
Metabolic (automatic) control pattern
Concerned with O2 delivery to mito and acid-base balance
Metabolic controller lies in the brainstem
Reticular activating system modulates the brainstem controller by affecting the state of alertness of the brain
Intrinsic breathing controllers
Medullary respiratory area
Respiratory neurons in the medulla (effect muscles of rib cage, diaphragm, abdomen)
Nucleus tractus solitarius (dorsal): discharge during inspiration
Nucleus retroambiguus (ventral): excited during inspiration and expiration
Pneumotaxic center (in the pons): influences the switching between inspiration and expiration
Behavioral (voluntary) control pattern
Higher brain center controllers in the thalamus and cerebralcortex are involved
Coordinates breathing with other volitional motor activities that make use of the lungs and chest wall (ie swallowing)
Rhythmic breathing depends on a continuous (tonic) inspiratory drive from the dorsal group, and on intermittent (phasic) expiratory inputs from the cerebrum, thalamus, cranial nerves, and ascending spinal cord sensory tracts
Thoracic mechanoreceptors (stretch receptors in walls of the airways) set breathing freq.
Stimulated by lung inflation and deflation; mainly influences inspiration
Neurons in ventral motor group (nucleus retroambiguus) are excited by lung inflation
Brainstem Mechanisms that generate respiratory rhythm
Central and peripheral chemoreceptors
Þ inspiratory neurons (dorsal motor group in nucleus tractus solitarius) Þ inspiratory muscle contraction
Central inspiratory activity and/or pulmonary stretch receptors via vagus nerve and/or stretch receptors in chest wall
Þ ventral motor group in nucleus tractus solitarius Þ activates inspiratory cutoff switch Þ inhibits dorsal motor group in nucleus tractus solitarius Þ inhibts inspiratory muscle contraction
Thus have tonic inspiratory activity that is inhibited only when sufficient sensory signals are received
Stimuli to segments T1 to T8 inhibit phrenic motor neuron activity and terminate inspiration
Stimuli to segments T9 to T12 excite intercostal and phrenic motor neurons and cause thoracic cavity to expand
Brainstem Respiratory Groups
four groups of respiratory neurons (two in each hemisphere); each group contains:
inspiratory: synapse with inspiratory muscles (external intercostal/diaphragm)
expiratory: synapse with expiratory muscles (internal intercostal/abdominal)
usually not to threshold during passive breathing, so expiration is passive
inspiration and expiration are mutually inhibitory (i.e., when one is active, the other is silent)
pneumotaxic center (group of neurons bilaterally in upper pons); controls breathing rate
not inherent pacemaker; receives impulses from other centers
inactivation leads to reduced breathing frequency, or "apneustic breathing"
modulate discharge intensity of medullary respiratory neurons to alter breathing
measure chemical status of blood (peripheral) and brain tissue (central chemoreceptors)
in carotid bodies (bifurcation of carotid) and aortic arch
mostly sensitive to low arterial [O2], but also respond to high [CO2] or high [H+]
responsible for most hypoxia-related stimulation of medullary respiratory centers
exact location not known, probably ventral midline medulla
more active at rest than peripheral
mostly measure [CO2], also [HCO3-] and pH
influenced by chemical composition of cerebrospinal fluid (CSF) and brain arterial blood
CSF bathes ventral surface of medulla CO2 diffuses here from arteries, H+ and HCO3- do not
Chemoreceptor Control of Breathing
Central chemoreceptors located near ventrolateral surface of the medulla
Account for 75% of CO2 induced increases in ventilation
Respond to changes in [H+] of surrounding brainstem interstitial fluid
Peripheral chemoreceptors (carotid bodies) account for remaining 25%