Human Physiology, 14th edition (2016)

554 Chapter 16

fluid, and in the P^ CO 2 , pH, and P^ O 2 of the blood. There are two

groups of chemoreceptors that respond to changes in P^ CO 2 , pH,

and P^ CO 2. These are the central chemoreceptors in the medulla

oblongata and the peripheral chemoreceptors. The peripheral

chemoreceptors are contained within small nodules associated

with the aorta and the carotid arteries, and they receive blood

from these critical arteries via small arterial branches. The

peripheral chemoreceptors include the aortic bodies, located

region of the cord. These spinal motoneurons are regulated,
either directly or via spinal interneurons, by descending axons
from the brain.
The respiratory rhythm is generated by a loose aggregation
of neurons in the ventrolateral region of the medulla oblongata,
which forms the rhythmicity center for the control of auto-
matic breathing. A group of neurons called the pre-Bötzinger
complex in the ventrolateral medulla is believed to generate the
inspiratory rhythm. Although it has intrinsic rhythmicity, and
its neurons have automatic bursts of activity, the mechanism by
which the pre-Bötzinger complex generates inspiratory rhythm
are not yet fully understood. Its automatic rhythm is influenced
by both excitatory and inhibitory synapses, and so can be modi-
fied by the requirements for speech and other motor activities.
Expiration is a passive process involving elastic recoil of the
lungs and thoracic structures during normal breathing at rest
(section 16.3). During exercise, however, expiration requires
active contraction of the abdominal and internal intercostal
muscles; this appears to be regulated by a second group of neu-
rons that function as a rhythmicity center active during exercise
but inactive at rest. This second rhythmicity center is located in
the medulla superior to the pre-Bötzinger complex.
The two rhythmicity centers send axons to higher motor neu-
rons in the medulla that, through synapses with spinal interneu-
rons, control lower motor neurons that innervate the respiratory
muscles. These higher motor neurons are divided anatomically
into a dorsal and a ventral respiratory group. Some of these
stimulate the phrenic nerve that innervates the diaphragm during
inspiration, for example, whereas others inhibit the phrenic nerve
during the passive portion of expiration.
The activity of the medullary rhythmicity center may be
influenced by centers in the pons. As a result of animal research
in which the brain stem is destroyed at different levels, two
respiratory control centers have been identified in the pons. One
area—the apneustic center —appears to promote inspiration by
stimulating the inspiratory neurons in the medulla. The other
area—the pneumotaxic center —seems to antagonize the apneus-
tic center and inhibit inspiration ( fig. 16.24 ). These are the roles
of the pons in the rhythmic control of breathing in experimental
animals; in humans, however, the functions of the pons in the
normal regulation of breathing is currently unclear.
The brainstem respiratory centers control breathing largely via
axons to the phrenic motor nuclei in cervical regions C3 through
C6 of the spinal cord. Lower motor neurons here send axons in
the phrenic nerves that control the diaphragm. This is why people
with spinal cord injuries at about C4 often cannot breathe indepen-
dently. A recent report demonstrated that rats with a comparable
injury could have their breathing restored by grafting a peripheral
nerve across the spinal cord lesion (forming a bridge for neuron
growth) and injecting an enzyme that reduces scar tissue.

Chemoreceptors

The automatic control of breathing is also influenced by input
from chemoreceptors, which are collectively sensitive to
changes in the pH of brain interstitial fluid and cerebrospinal

Figure 16.24 Approximate locations of the brain

stem respiratory centers. The rhythmicity center in the medulla

oblongata directly controls breathing, but it receives input from the

control centers in the pons and from chemoreceptors.

Medulla oblongata

Reticular formation

Apneustic area

Pneumotaxic

area

Midbrain

Brain stem

respiratory

centers

Pons

Rhythmicity area

CLINICAL APPLICATION

Ondine’s curse, a term taken from a German folktale,

refers to potentially fatal apnea during sleep as a result of

brainstem dysfunction. Voluntary regulation of breathing is

not affected because it involves descending corticospinal

tracts from the cerebral cortex. Most patients can breathe

adequately when awake, but during sleep the compromised

automatic control of breathing causes apnea that can range

from mild to potentially fatal. This condition may result from

trauma to the brainstem, but more commonly it is congeni-

tal. Called congenital central hypoventilation syndrome

( CCHS ), the defective gene has been identified and shown

to influence the retrotrapezoid nucleus of the medulla oblon-

gata. This area responds to a rise in PCO 2 and to input from

the carotid bodies. Patients with CCHS require a tracheos-

tomy and a mechanical ventilator throughout their lives.