Phys Ch 41
Respiratory Center
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Nervous system normally adjusts rate of alveolar ventilation almost exactly to demands of body so PO2 and PCO2
in arterial blood are hardly altered, even during heavy exercise and most other types of respiratory stress
Respiratory center of brain composed of several groups of neurons located bilaterally in medulla oblongata and
pons of brain stem
o Divided into dorsal respiratory group (dorsal portion of medulla that mainly causes inspiration), ventral
respiratory group (ventrolateral part of medulla that mainly causes expiration), and pneumotaxic center
(dorsal superior part of pons that mainly controls rate and depth of breathing)
Dorsal respiratory group – most of neurons located in nucleus of tractus solitarius (NTS), which is the sensory
termination of both vagal and glossopharyngeal nerves, which transmit sensory signals to respiratory center
from peripheral chemoreceptors, baroreceptors, and several types of receptors in lungs
o Basic rhythm of respiration generated mainly in dorsal respiratory group – emits inspiratory neuronal
action potentials, even with brain stem transected both above and below medulla
o Nervous signal transmitted to inspiratory muscles (mainly diaphragm) is not instantaneous burst of
action potentials – begins weakly and increases steadily in ramp manner for about 2 seconds in normal
inspiration, then abruptly ceases for about 3 seconds, which turns off excitation of diaphragm and
allows elastic recoil of lungs and chest wall to cause expiration – this is the reason we have steady
increase in volume of lungs during inspiration instead of inspiratory gasps
 Control of rate of increase of ramp signal so that during heavy respiration, ramp increases
rapidly and thus fills lungs rapidly
 Control of limiting point at which ramp suddenly ceases – usual method for controlling rate of
respiration (shortening ramp period shorten relaxation period, and rate of respiration increases)
Pneumotaxic center – located in nucleus parabrachialis of upper pons; transmits signals to inspiratory area –
inhibits dorsal respiratory group
o Primary effect is to control switch-off point of inspiratory ramp – weak signal causes long inspiration,
and strong signal causes short inspirations (filling lungs only slightly)
o Function of this is to limit inspiration and affect respiration rate
Ventral respiratory group of neurons – found in nucleus ambiguus rostrally and nucleus retroambiguus caudally
o Neurons remain almost totally inactive during normal quiet respiration
o Do not participate in basic rhythmical oscillation that controls respiration
o When respiratory drive for increased pulmonary ventilation becomes greater than normal, respiratory
signals spill over into ventral respiratory neurons from basic oscillating mechanism of dorsal respiratory
area, causing ventral respiratory area to contribute to extra respiratory drive
o Electrical stimulation of a few neurons in ventral group causes inspiration, whereas stimulation of others
causes expiration – important in providing powerful expiratory signals to abdominal muscles during very
heavy expiration, making ventral respiratory group more of an overdrive mechanism when high levels of
pulmonary ventilation are required
Sensory nerve signals from lungs help control respiration – stretch receptors in muscular portions of walls of
bronchi and bronchioles transmit signals through vagus nerves into dorsal respiratory group of neurons when
lungs become overstretched
o Activates feedback response that switches off inspiratory ramp and stops further inspiration (HeringBreuer inflation reflex) – increases rate of respiration by same mechanism as pneumotaxic center
o Hering-Breuer reflex not activated until tidal volume increases to more than 3 times normal breath, so it
is merely for preventing excess lung inflation rather than control of ventilation
Chemical Control of Respiration
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Excess CO2 or H+ act directly on respiratory center itself, causing greatly increased strength of both inspiratory
and expiratory motor signals to respiratory muscles
Oxygen does not have a significant direct effect on respiratory center, but acts almost entirely on peripheral
chemoreceptors in carotid and aortic bodies, which transmit appropriate nervous signals to respiratory center
for control of respiration
Chemosensitive area, located bilaterally just beneath the ventral surface of the medulla – highly sensitive to
changes in either blood PCO2 or H+
o Excites other portions of respiratory center in response to these changes
o Highly excited by changes in H+ to the point where this could be only important direct stimulus for these
neurons
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H do not cross blood-brain barrier easily, so changes in H+ in blood have less effect on stimulating
chemosensitive neurons than do changes in blood CO2, even though CO2 stimulation is secondary to H+
stimulation
o CO2 has indirect effect by reacting with water of tissues to form carbonic acid, which dissociates into H+
and HCO3- ions – these H+ have potent direct stimulatory effect on respiration
o CO2 can cross blood-brain barrier very easily; thus whenever blood PCO2 increases, so does PCO2 of
interstitial fluid of medulla and CSF
Excitation of respiratory center by CO2 is great for first few hours after blood PCO2 increases, but then gradually
declines over next 1-2 days
o Part of decline results from renal readjustment of H+ concentration in circulating blood back toward
normal by increasing blood bicarbonate, which binds with H+ in blood and CSF to reduce their
concentrations
o Over a period of hours, bicarbonate ions slowly diffuse through blood-brain and blood-CSF barriers and
combine directly with H+ adjacent to respiratory neurons, reducing H+ back to near normal
Hemoglobin-oxygen buffer system delivers almost exactly normal amounts of oxygen to tissues even with huge
changes in pulmonary PO2; therefore, except under special conditions, adequate delivery of oxygen can occur
despite changes in lung ventilation from below one-half normal to over 20x normal
o For special conditions where tissues do have a severe lack of oxygen, body has special mechanism for
respiratory control located in peripheral chemoreceptors outside brain respiratory center – responds
when blood oxygen falls too low
Peripheral Chemoreceptor System for Control of Respiratory Activity
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Chemoreceptors outside brain important for detecting changes in oxygen in blood – also respond to a lesser
extent to changes in CO2 and H+
o Transmit nervous signals to respiratory center in brain to help regulate respiratory activity
Most chemoreceptors are in carotid bodies, but there are some in aortic bodies and very few associated with
other arteries of thoracic and abdominal regions
Afferent nerve fibers of carotid bodies pass through Hering’s nerves to glossopharyngeal nerves and then to
dorsal respiratory area of medulla
Aortic bodies located along arch of aorta, and their afferent fibers pass through vagus nerves to dorsal
medullary respiratory area
Each chemoreceptor body receives its own blood supply through a minute artery directly from the adjacent
arterial trunk – these receive massive blood flow for their size, so percentage of oxygen removed from flowing
blood is virtually zero, so chemoreceptors are exposed at all times to arterial blood
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When oxygen concentration falls below normal, chemoreceptors become strongly stimulated (if arterial PO2 falls
to 30-60 mm Hg, which is when hemoglobin saturation with O2 decreases rapidly)
Increase in either CO2 or H+ concentration excites chemoreceptors and indirectly increases respiratory activity
o Direct effects of both CO2 and H+ on respiratory center itself are much more powerful than effects
mediated through chemoreceptors
o Stimulation by way of peripheral chemoreceptors occurs as much as 5x as rapidly as central stimulation,
so peripheral chemoreceptors important in increasing rapidity of response to CO2 at onset of exercise
Chemoreceptors have multiple glandular-like cells (glomus cells) that synapse directly or indirectly with nerve
endings
At arterial PO2 lower than 100 mm Hg, breathing rate doubles, and when arterial PO2 falls lower than 60 mm Hg,
breathing rate can increase to as much as 5x normal (if PCO2 and H+ are kept constant)
If one ascends a mountain slowly, they breathe much more deeply and can therefore withstand lower
atmospheric oxygen concentrations (acclimatization) – within 2-3 days, respiratory center in brain stem loses
about 4/5 of its sensitivity to changes in PCO2 and H+; therefore, excess ventilator blow-off of CO2 that normally
would inhibit increase in respiration fails to occur, and low oxygen can drive respiratory system to much higher
level of alveolar ventilation than under acute conditions
Regulation of Respiration during Exercise
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During exercise, especially in a healthy athlete, alveolar ventilation ordinarily increases almost exactly in step
with increased level of oxygen metabolism – arterial PO2, PCO2, and pH remain almost exactly normal
While transmitting motor impulses to exercising muscles, brain transmits collateral impulses into brain stem to
excite respiratory center
o When a person begins to exercise, large share of total increase in ventilation begins immediately on
initiation of exercise before any blood chemicals have had time to change
When a person exercises, direct nervous signals stimulate respiratory center almost the proper amount to
supply extra oxygen required for exercise and blow off extra CO2, but occasionally, nervous respiratory control
signals too strong or too weak, in which case, chemical factors play significant role in bringing about final
adjustment of respiration to keep O2, CO2, and H+ concentrations as normal as possible
At start of exercise, increased respiration is enough to decrease arterial PCO2 at first – probably anticipatory
stimulation of respiration – after 30-40 seconds, muscle metabolism balances this back to normal
Changes in arterial PCO2 during exercise have more of a stimulatory effect on ventilation than it would at rest
Brain’s ability to shift ventilatory response curve during exercise is partly a learned response – with repeated
periods of exercise, brain becomes progressively more able to provide proper signals required to keep blood
PCO2 at normal level – part of this is stored in cerebral cortex
Other Factors that Affect Respiration
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Epithelium of trachea, bronchi, and bronchioles supplied with pulmonary irritant receptors that are stimulated
to cause coughing and sneezing – may also cause bronchial constriction in such diseases as asthma and
emphysema
Alveolar walls have a few sensory nerve endings in juxtaposition to pulmonary capillaries (J receptors) that are
stimulated especially when pulmonary capillaries become engorged with blood or when pulmonary edema
occurs in such conditions as congestive heart failure – excitation gives a person a feeling of dyspnea
Activity of respiratory center may be depressed or inactivated by acute brain edema resulting from concussion –
partially blocks cerebral blood supply
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Occasionally respiratory depression from brain edema can be relieved temporarily by intravenous
injection of hypertonic solutions such as highly concentrated mannitol because this osmotically removes
some fluids of brain, relieving intracranial pressure and sometimes re-establishing respiration within a
few minutes
Most prevalent cause of respiratory depression and respiratory arrest is overdose of anesthetics or narcotics –
sodium pentobarbital depresses respiratory center considerably more than many other anesthetics such as
halothane
o Morphine is now used only as an adjunct to anesthetics because it greatly depresses respiratory center
while having less ability to anesthetize cerebral cortex
Periodic breathing – occurs in a number of disease conditions; person breathes deeply for a short interval, then
breathes slightly or not at all for another interval, with cycle repeating
o Cheyne-Stokes breathing – slowly waxing and waning respiration every 40-60 seconds
 When a person overbreathes, blowing off too much carbon dioxide from pulmonary blood while
increasing blood oxygen, it takes several seconds before changed pulmonary blood can be
transported to brain and inhibit excess ventilation
 When overventilated blood reaches brain respiratory center, center becomes depressed to an
excessive amount and opposite cycle begins
 This is dampened under normal conditions in healthy people because fluids of blood and
respiratory center control areas have large amounts of dissolved and chemically bound CO2 and
O2, so lungs cannot build up enough extra CO2 or depress O2 sufficiently in a few seconds to
cause next cycle of periodic breathing
 When a long delay occurs for transport of blood from lungs to brain, changes in CO2 and O2 in
alveoli can continue for many more seconds than usual, so storage capacities of alveoli and
pulmonary blood for gases are exceeded – this often occurs in patients with severe cardiac
failure because blood flow is slow, thus delaying transport of blood gases from lungs to brain
 Increased negative feedback gain in respiratory control areas can cause Cheyne-Stokes
breathing – change in blood CO2 or O2 causes far greater change in ventilation than normally
(increase in PCO2 can cause disproportionately high increase in ventilation rate) – occurs in
patients with brain damage, which often turns off respiratory drive entirely for a few seconds,
then extra intense increase in blood CO2 turns it back on with great force – usually a prelude to
death from brain malfunction
 PCO2 of pulmonary blood changes in advance of PCO2 of respiratory neurons, but depth of
respiration corresponds with PCO2 in brain, not PCO2 in pulmonary blood where ventilation is
occurring
Sleep Apnea
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Occasional apneas occur during normal sleep, but in sleep apnea, frequency and duration are greatly increased
with episodes of apnea lasting for 10 seconds or longer and occurring 300-500 times a night
Obstructive sleep apnea – caused by obstruction of upper airways, especially pharynx, or by impaired CNS
respiratory drive
o During sleep, muscles of pharynx relax but airway passage remains open enough to permit adequate
airflow
o Individuals with especially narrow pharynx can have completely closure of pharynx during sleep so that
air cannot flow into lungs
o Loud snoring or labored breathing occur soon after falling asleep – snoring proceeds, becoming louder,
then interrupted by long silent period of apnea, where PO2 decreases and PCO2 increases, greatly
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stimulating respiration (sudden attempts to breathe, which result in loud snorts and gasps followed by
snoring and repeated episodes of apnea)
o Periods of apnea and labored breathing cause fragmented, restless sleep
o Patients often have daytime drowsiness, increased SNS activity, high hear rates, pulmonary and systemic
hypertension, and greatly elevated risk for cardiovascular disease
o Most commonly occurs in older, obese people where there is increased fat deposition in soft tissues of
pharynx or compression of pharynx due to excessive fat masses in neck
o Can be associated with very large tongue, enlarged tonsils, or certain shapes of palate that greatly
increase resistance to flow of air to lungs during inspiration
o Most common treatments include surgical removal of fat tissue at back of throat
(uvulopalatopharyngoplasty), removal of enlarged tonsils or adenoids, or tracheostomy – can also be
treated with nasal ventilation with continuous positive airway pressure (CPAP)
Central sleep apnea – CNS drive to ventilatory muscles transiently ceases
o Can be caused by damage to central respiratory centers or abnormalities of respiratory neuromuscular
apparatus
o Patients may have decreased ventilation when they are awake, though they are fully capable of normal
voluntary breathing
o During sleep, breathing disorders usually worsen, resulting in more frequent episodes of apnea that
decrease PO2 and increase PCO2 until critical level is reached that eventually stimulates respiration –
causes restless sleep and clinical features similar to obstructive sleep apnea
o Instability of respiratory drive can result from strokes or other disorders that make respiratory centers
of brain less responsive to stimulatory effects of CO2 and H+, but most cases have unknown causes
o Patients are extremely sensitive to small doses of sedatives or narcotics, which further reduce
responsiveness of respiratory centers to stimulatory effects of CO2
o Medications that stimulate respiratory centers can be helpful, but often CPAP at night necessary