Control of Respiration
The intrinsic rhythmicity of respiration is primarily
controlled by specific neural areas located in the reticular
substance of the medulla and pons of the brain.
These neural areas possess monitoring, stimulating,
and inhibiting properties that continually adjust the
ventilatory patterns to meet specific metabolic needs.
Also received and coordinated in these respiratory
neural areas are the signals transmitted by the cerebral
cortex during a variety of ventilatory maneuvers such as
talking, singing, sniffing, coughing, or blowing into a
(1) the function of the major respiratory
components of the medulla.
(2) the influence of the pontine respiratory
centers on the medulla.
(3) the major monitoring systems that
influence the respiratory components of
(4) the reflexes that influence ventilation is
Major Respiratory Components
of the Medulla
THE RESPIRATORY COMPONENTS
OF THE MEDULLA OBLONGATA
• Two groups of respiratory neurons in the
reticular formation of medulla are
responsible for coordinating the intrinsic
rhythmicity of respirations.
(1) the dorsal respiratory groups
(2) the ventral respira-tory groups
.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.
DORSAL RESPIRATORY GROUP
• The dorsal respiratory groups (DRGs) are located
bilaterally in the posterior region of the medulla in an
area called the nucleus of the tractus solitarius.
• The DRGs consist chiefly of inspiratory neurons.
• The DRG neurons receive inspiratory impulses from
several different specialized monitoring systems
throughout the body.
• These monitoring systems include signals from the
central chemoreceptors,peripheral chemoreceptors,
stretch receptors, peripheral proprioceptors, and higher
DORSAL RESPIRATORY GROUP
• The DRG neurons continuously evaluate
and prioritize the signals and, depending
on the respiratory needs, send neural
impulses every few seconds to the
muscles of inspiration, i.e., the diaphragm
and the external intercostal muscles.
• The DRG neurons are believed to be
responsible for the basic rhythm of
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).
DORSAL RESPIRATORY GROUP
• Under normal conditions, the DRG neurons
trigger inspiratory impulses at a rate of 12 to 15
• The neural signals of the DRGs continue for
about 1to 2 seconds and then cease abruptly,
causing the muscles of inspiration to relax.
• During exhalation, which lasts for about 2 to 3
seconds, the natural elastic recoil forces of the
lungs cause the lungs to deflate.
VENTRAL RESPIRATORY GROUP
• The ventral respiratory groups (VRGs) are located bilaterally
in two different areas of the medulla .
• They contain both inspiratory and expiratory neurons.
• The VRG neurons are further subdivided into the nucleus
ambiguus,nucleus retroambigualis, and Botzinger’s
• The nucleus ambiguus contains primarily inspiratory
neurons that innervate the laryngeal and pharyngeal muscles
via the vagus nerve.
• When stimulated, the vocal cords of the larynx abduct, causing
airway resistance to decrease.
VENTRAL RESPIRATORY GROUP
• The nucleus retroambigualis is divided into the
rostral (toward the head) and caudal (toward the tail)
• The rostral VRG area is composed mainly of
inspirator neurons that stimulate the diaphragm and
external intercostal muscles similar to the DRG
• The caudal VRG area is composed mainly of
expiratory neurons that stimulate the internal
intercostal and abdominal expiratory muscles.
• The Botzinger’s complex contains only expiratory
neurons that inhibit the discharge of the inspiratory
neurons of the DRG and VRG.
VENTRAL RESPIRATORY GROUP
• During normal quiet breathing, the VRG is
almost entirely dormant, because the lungs
passively return to their original size by virtue
of their own elastic recoil forces.
• During heavy exercise or stress, however, the
expiratory neurons of the VRG actively send
impulses to the muscles of exhalation (i.e.,
abdominal muscles) and the accessory muscles
of inspiration that are innervated by the vagus
THE INFLUENCE OF THE PONTINE
RESPIRATORY CENTERS ON THE
RESPIRATORY COMPONENTS OF
THE MEDULLA OBLONGATA
• The pontine respiratory centers consist of
the apneustic center and the
• It appears that these centers function to
some degree to modify and fine-tune the
rhythmicity of breathing.
• The apneustic center is located in the lower
portion of the pons .
• It continually sends neural impulses that
stimulate the inspiratory neurons of theDRGs
and VRGs in the medulla.
• If unrestrained, a prolonged or gasping type of
inspiration (breath hold) occurs. This inspiratory
maneuver is called apneustic breathing.
• Under normal conditions, however, the
apneustic center receives several different
inhibitory signals that suppress its function, thus
permitting expiration to occur.
• Research suggests that the most important
inhibitory signals are elicited from the
pneumotaxic center and from afferent impulses
that originate from lung inflation (Hering-Breuer
• Breathing becomes deep and slow when the
pneumotaxic neurons are cut in animal
brain-transection studies, which supports the
evidence that the apneustic center is
normally inhibited by the pneumotaxic center.
• The pneumotaxic center is located bilaterally in the
upper one-third of the pons,in a reticular substance
called the nucleus parabrachialis medialis and
• The pneumotaxic center receives neural impulses
via the vagus from (1) the lung inflation reflex (see
Hering-Breuer reflex and
(2) the stretch receptors located in the intercostal
muscle of the thorax.
• In response to these neural signals, the pneumotaxic
center sends out inhibitory impulses to the inspiratory
center of the medulla, causing the inspiratory phase to
• Strong signals from the pneumotaxic center decrease
the inspiratory time and increases the respiratory rate.
• Weak signals increase the inspiratory time
(increased tidal volumes) and decrease the respiratory
• Research suggests, however, that the major function
of the pneumotaxic center is to (1) limit the
inspiratory phase of a ventilatory cycle, and (2) keep
the apneustic center from causing an “apneustic” or
• pneumotaxic center works to enhance and fine-tune the
rhythmicity of the breathing pattern.
• This is supported by animal braintransection studies that show
that when the pons is separated from the medulla, an irregular
breathing pattern results.
• pneumotaxic center is closely related to the so-called panting
center in animals such as dogs.
• For example, when a dog becomes overheated, the panting
center causes it to breathe with rapid, shallow breaths that
evaporate large amounts of water from the its upper airways,
thus cooling the animal.
• In humans,the pneumotaxic center appears to have an
effect similar to the Hering-Breuer reflex.
CONDITIONS THAT DEPRESS THE RESPIRATORY
COMPONENTS OF THE MEDULLA OBLONGATA
(1) reduced blood flow through the medulla as a result
of excess pressure caused by a cerebral edema or
some other intracerebral abnormality,
(2) Acute poliomyelitis, and
(3) Ingestion of drugs that depress the central
MONITORING SYSTEMS THAT INFLUENCE THE
RESPIRATORY COMPONENTS OF THE MEDULLA
The major known monitoring systems are the
(1) Central Chemoreceptors
(2) Peripheral Chemoreceptors
• The most powerful stimulus known to influence the
respiratory components (DRG and VRG) of the medulla
is an excess concentration of hydrogen ions [H] in the
cerebrospinal fluid (CSF).
• The central chemoreceptors, which are located
bilaterally and ventrally in the substance of the medulla,
are responsible for monitoring the H ion concentration of
• In fact, a portion of the central chemoreceptors is
actually in direct contact with the CSF.
MECHANISM OF CENTRAL
• As the CO2 level increases in the arterial blood (e.g., during
hypoventilation), the CO2 molecules diffuse across ,the blood-brain
• The bloodbrain barrier is very permeable to CO2 molecules but
relatively impermeable to H and HCO3 ions.
• As CO2 moves into the CSF, it forms carbonic acid
CO2 + H2O = H2CO3 = H + HCO3
• Because the CSF lacks hemoglobin and carbonic anhydrase and
has a relatively low bicarbonate and protein level, the overall
buffering system in the CSF is very slow.
• The liberated H ions cause the central
chemoreceptors to transmit signals to the
respiratory component in the medulla which, in
turn, increases the alveolar ventilation.
• The increased ventilation reduces the PaCO2
and, subsequently, the PCO2 in the CSF.
• As the PCO2 in the CSF decreases, the H+
concentration of the CSF also falls.
• This action decreases the stimulation of the
central chemoreceptors causes alveolar
ventilation to decrease.
• The peripheral chemoreceptors are special
oxygen-sensitive cells that react to the
reductions of oxygen levels in the arterial blood.
• They are located high in the neck at the
bifurcation of the internal and external carotid
arteries and on the aortic arch.
• They are close to, but distinct from the
• The peripheral chemoreceptors are also called
the carotid and aortic bodies.
• The carotid and aortic bodies are composed of epithelial-
like cells and neuron terminals in intimate contact with
the arterial blood.
• When activated by a low Pao2 afferent (sensory) signals
are transmitted to the respiratory components in the
medulla by way of the glossopharyngeal nerve (ninth
cranial nerve) from the carotid bodies and by way of the
vagus nerve (tenth cranial nerve) from the aortic bodies.
• This action, in turn, causes efferent (motor) signals to be
transmitted to the respiratory muscles, causing
ventilation to increase.
• Compared with the aortic bodies, the carotid bodies play
a much greater role in initiating an increased ventilatory
rate in response to reduced arterial oxygen levels.
• the peripheral chemoreceptors are not significantly activated until the
oxygen content of the inspired air is low enough to reduce the to pao2 60
mm Hg (sao2 about 90 percent).
• Beyond this point, any further reduction in the pao2 causes a marked
increase in ventilation.
• Suppression of the peripheral chemoreceptors is seen, however, when the
pao2 falls below 30 mm Hg.
• In the patient with a pao2 low and a chronically high paco2 level (e.g.,
endstage emphysema), the peripheral chemoreceptors may be totally
responsible for the control of ventilation.
• This is because a chronically high CO2 concentration in the CSF inactivates
the H sensitivity of the central chemoreceptor—that is, HCO3 moves into
the CSF via the active transport mechanism and combines with H, thus
returning the pH to normal.
• A compensatory response to a chronically high CO2 concentration,
however, is the enhancement of the sensitivity of the peripheral
chemoreceptors at higher CO2 levels
The effect of low levels PaO2 on
• peripheral chemoreceptors are specifically
sensitive to the po2 of the blood and relatively
insensitive to the oxygen content of the blood.
• there are certain conditions in which the pao2 is
normal (and, therefore, the peripheral
chemoreceptors are not stimulated), yet the
oxygen content of the blood is dangerously low.
• Such conditions include chronic anemia, carbon
monoxide poisoning, and methemoglobinemia.
Other Factors That Stimulate the
• Although the peripheral chemoreceptors are
primarily stimulated by a reduced PaO2 level
• They are also activated by a decreased pH
(increased H level).
• This is an important feature of the peripheral
chemoreceptors, because there are many
situations in which a change in arterial H ion
levels can occur by means other than a primary
change in the PCO2.
• In fact, because the H ions do not readily move
across the blood-brain barrier, the peripheral
chemoreceptors play a major role in initiating
ventilation whenever the H ion concentration
increases for reasons other than an
• For example, the accumulation of lactic acid or
ketones in the blood stimulates hyperventilation
almost entirely through the peripheral
• The peripheral chemoreceptors are also stimulated by
(1)Hypoperfusion (e.g., stagnant hypoxia),
(4)Direct effect ofPaCO2
• The response of the peripheral chemoreceptors to PaCO2
stimulation, however, is minor and not nearly so great as the
response generated by the central chemoreceptors.
• The peripheral chemoreceptors do respond faster than the central
chemoreceptors to an increased PaCO2
• This occurs because the peripheral chemoreceptors are stimulated
directly by the CO2 molecule, whereas the central chemoreceptors
are stimulated by the H generated by the CO2 hydration reaction in
the CSF—a reaction that occurs slowly in the absence of carbonic
Other Responses Activated by
the Peripheral Chemoreceptors.
• Peripheral vasoconstriction
• Increased pulmonary vascular resistance
• Systemic arterial hypertension
• Increase in left ventricular performance
REFLEXES THAT INFLUENCE
• The Hering-Breuer reflex is generated by stretch receptors, located
in the walls of the bronchi and bronchioles, that become excited
when the lungs overinflate.
• Signals from these receptors travel through the vagus nerve to the
respiratory components in the medulla, causing inspiration to cease.
• In essence, the lungs themselves provide a feedback mechanism to
• Instead of a reflex to control ventilation, the Hering-Breuer reflex
appears to be a protective mechanism that prevents pulmonary
damage caused by excessive lung inflation.
• The significance of the Hering-Breuer reflex in the adult at normal
tidal volumes is controversial; it appears to have more significance
in the control of ventilation in the newborn.
• When the lungs are compressed or deflated, an
increased rate of breathing results.
• Some researchers believe that the increased rate of
breathing may be due to the reduced stimulation of
receptors serving the Hering-Breuer reflex rather than to
the stimulation of specific deflation receptors.
• Others, however, think that the deflation reflex is not
due to the absence of receptor stimulation of the Hering-
Breuer reflex, because the re-flex is still seen when the
temperature of the bronchi and bronchioles is less than
• The Hering-Breuer reflex is not active when the bronchi
and bronchioles are below this temperature.
• When the lungs are exposed to noxious gases,
the irritant receptors may also be stimulated.
• The irritant receptors are subepithelial
mechanoreceptors located in the trachea,
bronchi, and bronchioles.
• When the receptors are activated, a reflex
response causes the ventilatory rate to increase.
• Stimulation of the irritant receptors may also
produce a reflex cough and bronchoconstriction.
• An extensive network of free nerve endings, called C-fibers, are
located in the small conducting airways, blood vessels, and
interstitial tissues between the pulmonary capillaries and alveolar
• The C-fibers located near the alveolar capillaries are called
juxtapulmonary-capillary receptors, or J-receptors.
• These receptors react to certain chemicals and to mechanical
• For example, they are stimulated by alveolar inflamation, pulmonary
capillary congestion and edema, humoral agents (e.g., serotonin,
bradykinin), lung deflation, and emboli.
• When the J-receptors are stimulated, a reflex response triggers a
rapid, shallow breathing pattern.
• Peripheral proprioceptors are located in the muscles, tendons,
joints, and pain receptors in muscles and skin.
• When stimulated, the proprioceptors send neural impulses to the
• The medulla, in turn, sends out an increased number of inspiratory
• This may explain, in part, why moving an individual’s limbs (for
example, during a drug overdose), or producing prolonged pain to
the skin, stimulates ventilation.
• Sudden pain causes a short period of apnea, whereas prolonged
pain causes the breathing rate to increase.
• The proprioceptors in the joints and tendons are also believed to
play an important role in initiating and maintaining an increased
respiratory rate during exercise.
• The more joints and tendons are involved, the greater the respiration
• Strong emotions can activate sympathetic
centers in the hypothalamus, which can alter
• For example, excitement causes the respiratory
rate to increase.
• increased body temperature causes the
respiration rate to increase,
• decreased body temperature produces the
opposite effect. For instance, a sudden cold
stimulus (e.g., plunging into very cold water) can
cause the cessation of breathing—or at the very
least, a gasp.
REFLEXES FROM THE AORTIC AND CAROTID
• The normal function of the aortic and carotid sinus
baroreceptors, located near the aortic and carotid
peripheral chemoreceptor is to initiate reflexes that
(1) a decreased heart and ventilatory rate in response to
an elevated systemic blood pressure and
(2) an increased heart and ventilatory rate in response to
a reduced systemic blood pressure.
• The respiratory neurons of the medulla
oblongata coordinate both the involuntary
and voluntary rhythm of breathing.
• The respiratory center of the medulla receives
neural impulses from several different areas
throughout the body, evaluates and prioritizes
the signals, and elicits neural impulses to the
muscles of ventilation based on the metabolic
need of the body.
(1) the respiratory components of the medulla, including
the dorsal respiratory groups (DRGs) and ventral
respiratory groups (VRGs).
(2) the pontine centers on the medulla, including the
apneustic center and pneumotaxic center;
(3) the monitoring systems that influence the medulla,
including the central chemoreceptors and peripheral
(4) the reflexes that influence ventilation, including the
Hering-Breuer reflex, deflation reflex, irritant
reflex, juxtapulmonary-capillary receptor reflex,
peripheral proprioceptor reflex, hypothalamic
controls, and reflexes from the aortic and carotid