The regulation of breathing is based in the body's acid/base balance. The Central Chemoreceptors (CCR), primarily responsible for the breathing stimulation, are affected by the PaCO2. The responsiveness of the peripheral receptors is tied to the level of pH and PaCO2. Together these provide the ultimate in servo-control - sensors provide feedback that increase or decrease breathing.
The rhythmic cycle of breathing originates in the medulla. Higher brain centers (voluntary control), systemic receptors, and reflexes modify the medulla's output. However, no truly separate inspiratory and expiratory centers have been identified.
The medulla does contain several widely dispersed groups of respiratory-related neurons that form dorsal and ventral respiratory groups.
Fig. 9-1. Schematic illustration of the respiratory components of the lower brainstem (pons and medulla oblongata).
PNC = pneumotaxic center; APC = apneustic center; DRG = dorsal respiratory group; VRG = ventral respiratory group; CC = central chemoreceptors.
Composed mainly of inspiratory neurons located bilaterally in the medulla, the DRG controls the basic rhythm of breathing by triggering inspiratory impulses.
These neurons send impulses to the motor nerves of diaphragm and external intercostal muscles.
DRG nerves extend into the VRG, but the VRG neurons do not extend into the DRG.
Vagus and glossopharyngeal nerves bring sensory impulses to the DRG from the lungs, airways, peripheral chemoreceptors, and joint proprioceptors.
Input modifies the breathing pattern.
Contain both inspiratory and expiratory neurons located bilaterally in the medulla and primarily active in exercise and stress.
VRG sends inspiratory impulses to
Laryngeal and pharyngeal muscles - (from neurons located in the nucleus ambiguus)
Diaphragm and external intercostals - (from neurons located in the rostral area of the nucleus retroambigualis)
Other VRG neurons send expiratory signals to abdominal muscles and internal intercostals - (from neurons in the caudal area)
Inspiratory ramp signal: Interaction between the DRG and VRG inspiratory neurons:
Signal starts low and gradually increases to produce a smooth inspiratory effort instead of a gasp.
Fig.9-2. Neural impulses from the respiratory center travel to the diaphragm by way of the right and left phrenic nerves. The cervical, thoracic, and lumbar motor nerves stimulate the external intercostal muscles (accessory muscles of inspiration).
The pons modifies the output of medullary centers.
Two pontine centers are the apneustic and pneumotaxic.
Stimulates the inspiratory neurons of the DRG and VRG.
Its function only identified by cutting connection to medullary centers (don't know what you've got till its gone!)
Over stimulation from the apneustic center results in apneustic breathing which is characterized by long gasping inspirations interrupted by occasional expirations.
Sends inhibitory signals to the inspiratory center of the medulla
Controls "switch-off," so controls inspiratory time.
Increased signals increase RR, while weak signals prolong IT and increase VT.
Receptors located in the visceral pleura, walls of the bronchi and bronchioles.
Lung distention causes stretch receptors to send inhibitory signals to DRG, stopping further inspiration.
In adults active only on large VT (>800 ml)
Regulates rate and depth of breathing during moderate to strenuous exercise
Viewed as a protective mechanism.
Sudden lung collapse results in hyperpnea as seen in pneumothoraces.
May maintain large VT during exercise and deep sighs
May be responsible for babies first breaths at birth
Subepithelial mechanoreceptors in the trachea bronchi and bronchioles
Stimulated by inhaled irritants or mechanical factors
Cause bronchospasm, cough, sneeze, tachypnea, and narrowing of glottis
These are vasovagal reflexes.
In hospital triggered by
Suctioning, bronchoscopy, endotracheal intubation
Irritation reponse can be anesthetized by instilling lidocaine into the airway through the endotracheal (breathing) tube.
C-fibers - located in the small airways, blood vessels, interstitial tissues between the pulmonary capillaries and alveolar walls
J-fibers - Located in lung parenchyma juxtacapillary
Stimulated by pneumonia, CHF, pulmonary edema
Cause rapid, shallow breathing and dyspnea
Found in muscles, tendons, joints, and pain receptors
Movement stimulates hyperpnea.
Moving limbs, pain, cold water all stimulate breathing in patients with respiratory depression
Fig. 9-3. The relationship of the blood-brain barrier (BBB) to CO2, HCO3, and H+. CO2 readily crosses the BBB. H+ and HCO3 do not readily cross the BBB. H+ and HCO3 require the active transport system to cross the BBB. CSF = cerebrospinal fluid.
Located bilaterally in the medulla
Stimulated directly by H+ ions in the cerebrospinal fluid, indirectly by CO2
The BBB is almost impermeable to H+ and HCO3– but CO2 freely crosses from the blood to the cerebrospinal fluid.
In CSF, CO2 is hydrolized, releasing H+.
An increased CO2 therefore increases H+ in CSF which stimulates the neurons to cause hyperventilation to restore normal levels pH and CO2.
increased 2–3 L/min for 1–mm Hg rise in PaCO2.
In normal circumstances our primary stimulus to breaths is PaCO2. This is an important point to remember as it is not unusual for patients on mechanical ventilation to be over-ventilated. If their CO2 is less than the level it takes to stimulate the central chemoreceptors then they will not initiate a breath on their own, and this can be misinterpreted as an apneic period.
Located in the aortic arch and bifurcations of common carotid arteries
Fig. 9-4. Location of the carotid and aortic bodies (the peripheral chemoreceptors).
The carotid bodies more responsive to a decrease in PaO2 than the aortic bodies.
This response is frequently referred to as the "Hypoxic drive" however current research indicates that Hhypoxemia increases receptors sensitivity for H+, and it is this that stimulates a increse in minute ventilation.
⇓PaO2 causes ⇑ for any pH, and vice versa.
In severe alkalosis, hypoxemia has little affect on .
Only affected by PaO2, not CaO2 (so in conditions such as anemia or COHb, even though the patient's total O2 content is reduced, the periperhal chemoreceptor's are not stimulated)
Not a significant response until PaO2 falls to ~60 mm Hg (corresponds to an SaO2 of 90%) A further fall results in sharp increase in VE. However this response limits out at a PaO2 of 30 mm Hg, with suppression of respiration occuring below that level.
Fig. 9-5. Schematic illustration showing how a low PaO2 stimulates the respiratory components of the medulla to increase alveolar ventilation.
Once the PaO2 fall to 60 then, hypoxemia is the most common cause of hyperventilation.
Fig. 9-6. The effect of low PaO2 levels on ventilation.
Less responsive than central chemoreceptors (CCRs)
One-third of hypercapnic response, but a more rapid response to changes in [H+]
Influenced by fixed acids such as Lactic acid, ketones
In hyperoxia, PCRs are almost totally insensitive to changes in PaCO2, so any response is due to CCRs responding to changes in CSF [H+].
Fig. 9-7. The effect of PaO2 on ventilation at three different PaCO2 values. Note that as the PaCO2value increases, the sensitivity of the peripheral chemoreceptors increases.
Fig. 9-8. The accumulation of lactic acids leads to an increased alveolar ventilation primarily through the stimulation of the peripheral chemoreceptors.
Coexisting acidosis, hypercapnia, and hypoxemia maximally stimulate PCRs
Hypoperfusion (stagnant or circulatory hypoxia)
Nicotine - which also causes
Increased pulmonary vascular resistance
Systemic arterial hypertension
Increased left ventricular performance
A sudden rise in PaCO2 in the normal person causes an immediate rise in VE. In slow-rising PaCO2 (such as seen in the development of severe COPD), the kidneys retain HCO3–, which maintains CSF pH, so no hyperventilation response is trigger by the chronically elevated CO2.
Hypoxemia is always present in severe COPD due to severe mismatches in V/Q.
An increased FIO2 raises the PaO2 making the PCR less sensitive to [H+] resulting in a higher PaCO2
O2 therapy may cause a sudden rise in PaCO2 in severe COPD with chronic hypercapnic. This rise in CO2 may be significant enough to cause a condition known as CO2 narcosis - the patient becomes obtunded and non-responsive, further hypoventilation occurs, and can lead to coma and death.
Possible explanations include
Hypoxic drive is removed (traditional view).
⇑FIO2 may worsen V/Q mismatch
Hypoxic pulmonary vascoconstriction is reversed to poorly ventilated alveoli
⇑FIO2 may make patient susceptible to absorption atelectasis.
The diagnosis of "COPD" does NOT signify chronic hypercapnia or that O2 therapy will induce hypoventilation. Only an arterial blood gas can show CO2 retention and compensation by the kidneys.
These characteristics are only in end-stage disease.
Present in small percent of COPD patients
Concern about O2-induced hypercapnia and acidemia is not warranted in most COPD patients.
O2 should NEVER be withheld in hypoxemic COPD patients as tissue oxygenation is an overriding priority.
Be prepared to provide MV to the rare COPD patient who does have severe hypoventilation due to oxygen therapy.
Acute rises in PaCO2 continues to stimulate the CCRs.
Resulting ventilatory response is depressed due to chemical and mechanical reasons.
Increased HCO3– prevents as large a fall in pH, as would be seen in a healthy patient.
Abnormal mechanics impair lung ability to increase VE.
Strenuous exercise can increase CO2 production and O2 consumption 20-fold.
Ventilation normally keeps pace so all ABG values are held constant.
Mechanism for increased VE poorly understood: may be
CNS sends concurrent signals to skeletal muscles and to medullary respiratory centers.
Joint movement stimulates proprioceptors, which send excitatory signals to medullary centers.
May also be due to repeated experience causing anticipatory changes in ventilation
Fig. 9-9. The respiratory center coordinates signals from the higher brain region, great vessels, airways,
lungs, and chest wall. (+) = increased ventilatory rate; (-) = decreased ventilatory rate.
Absence of breathing. (Ap-knee-a)
Normal breathing (Eup-knee-a)
Only able to breathe comfortable in upright position (such as sitting in chair), unable to breath laying down, (Or-thop-knee-a)
Subjective sensation related by patient as to breathing difficulty
Paroxysmal nocturnal dyspnea - attacks of severe shortness of breath that wakes a person from sleep, such that they have to sit up to catch their breath - common in patient's with congestive heart failure.
Figure 2-38 Hyperpnea: Increased depth of breathing (Hi-perp-knee-a)
Increased volume with or without and increased frequency (RR), normal blood gases present.
Figure 2-39 Hyperventilation. Increased rate (A) or depth (B), or combination of both.
"Over" ventilation - ventilation in excess of the body's need for CO2 elimination. Results in a decreased PaCO2, and a respiratory alkalosis.
Hypoventilation. Decreased rate (A) or depth (B), or some combination of both.
"Under" ventilation - ventilation that is less than needed for CO2 elimination, and inadequate to maintain normal PaCO2. Results in respiratory acidosis.
Can be a slow rate with normal tidal volumes such that the total minute ventilation is inadequate.
Can be a normal rate but with such low tidal volumes that air exchange is only in the dead space and not effective.
Increased frequency without blood gas abnormality
Kussmaul's respiration. Increased rate and depth of breathing over a prolonged period of time. In response to metabolic acidosis, the body's attempt to blow off CO2 to buffer a fixed acid such as ketones. Ketoacidosis is seen in diabetics.
Gradual increase in volume and frequency, followed by a gradual decrease in volume and frequency, with apnea periods of 10 - 30 seconds between cycle. Described as a crescendo - decrescendo pattern. Characterized by cyclic waxing and waning ventilation with apnea gradually giving way to hyperpneic breathing.
Seen with low cardiac output states (CHF) with compromised cerebral perfusion
Creates lag of CSF CO2 behind arterial PaCO2 and results in characteristic cycle. Delayed sensitivity to CO2 changes- during apnea the CO2 increase above the threshold for stimulus but the brain is slow to respond, then it over shoots by hyperventilating and the signal to reduce ventilation is slow to be recognized.
Similar to CSR but VT is constant except during apneic periods. Short episodes of rapid, deep inspirations followed by 10 - 30 second apneic period.
Seen with patients with elevated ICP as seen in meningitis
Indicates damage to pons
May be caused by head trauma, severe brain hypoxia, or lack of cerebral perfusion
Mid brain and upper pons damage
Medulla respiratory centers are not responding to appropriate stimuli.
Associated with head trauma, cerebral hypoxia, and narcotic suppression
CO2 plays an important role in autoregulation of CBF mediated through its formation of H+.
Increased CO2 dilates cerebral vessels and vice versa.
In traumatic brain injury (TBI), the brain swells acutely. Head is a fixed volume container - cannot expand. When bleeding or swelling occurs in the brain pressures rapidly increase. Raising ICPs exceed cerebral arterial pressure and brain perfusion stops.
Cerebral hypoxia/ischemia - brain death
Mechanical hyperventilation can lower PaCO2, which results in vasoconstriction in cerebral vessels, reduction of swelling and ICP.
Controversial as reduces O2 and CBF to injured brain.
Only effective for the first 24 hours.
Current practice is to treat perfusion pressures pharmacologically rather then use hyperventilation.
All agree must avoid hypoventilation in TBI patients.