Ten/Thirteen Flashcards
In general terms, in what ways does the brain regulate respiration and how?
As demonstrated in earlier chapters, ventilation is simple
in concept but complex in execution. The brain controls the
basic pattern of breathing, integrating multiple infl uences
within lower motor neurons of the brainstem and spinal cord
to drive pharyngeal, laryngeal, diaphragmatic, intercostal, and
other respiratory muscles. Recall that
.V
E (L/min) = VT · f. The
central nervous system regulates respiration by controlling the
rhythm and pattern of its output to respiratory muscles, adjusting
f, VT or both, depending on overall ventilatory needs for a
greater or lesser
.V
E (Fig. 11.1).
Describe the central rhythm generator, i.e. its name, its function, how its work is modified, its location.
The frequency of respiration, or its rhythm, is intrinsic to the
brainstem. All vertebrates that use tidal oscillations for the
exchange of O2 and CO2 in their lungs have such movements
generated in their medulla oblongata. Indeed surgically
isolated brainstem preparations, lacking afferent inputs from
chemoreceptors and mechanoreceptors, still produce rhythmic
outputs along the same cranial nerves as during normal respiration.
One critical rhythm generator within a small area of the
medulla and rostral to the obex is called the pre-Bötzinger
complex. Bilateral lesions in this portion of the medulla induce
complete respiratory arrest in humans. Whether this rhythmic
discharge initiates within individual pacemaker cells, or from
a network of such cells, remains a matter of debate. At this
point, it is important to understand that a rhythm is constantly
generated by the medulla, a rhythm that is modifi able by afferent
input from sensory receptors.
Describe the central pattern generator. What does it do and why? How does it accomplish this? What things modify both rhythm and pattern? What things modify just pattern?
The central pattern generator, or the brainstem output controlling all muscles involved in respiration, is much more complex. This pattern generator algebraically sums all the
afferent inputs to produce well-coordinated activations of the
diaphragm, intercostal muscles, and abdominal muscles, and
if needed, the accessory muscles of respiration. Like respiratory
rhythm, the goal of such pattern generation is maintenance
of normal Pao2, Paco2, and pHa. Extreme examples
of modulating both the rhythm and pattern of respiration are
seen during rigorous exercise and ascents to high altitude.
The pattern of respiration is also modulated by events like
coughing, speech, sleep, vomiting, micturition, and defecation,
particularly as the latter may mimic a Valsalva maneuver.
Although some of these events are episodic or relatively
infrequent, they can affect the normal respiratory pattern in
dramatic ways.
Describe 8 different define patterns of respiration.
Eupnea: is normal, quiet breathing at rest. Individuals
are usually unaware of it.
Tachypnea or polypnea: is an increase in f without an
increase in VT . Tachypnea is not a normal stress response,unless hyperthermia or other factor has induced panting.
Hyperpnea or hyperventilation: denotes an increase
in pulmonary ventilation involving both VT and f, but
without the subjectively stressful sensations of dyspnea
(Fig. 11.2).
Dyspnea: is the sensation of inadequate or stressful
respiration, with exaggerated awareness of one’s need
for increased respiratory effort. Dyspnea implies labored
breathing, often involving accessory respiratory muscles.
Many stimuli induce dyspnea.
Cheyne-Stokes respiration: is the most common
form of abnormal breathing, with weak respiratory
efforts that decrease to an apnea and then increase
to hyperpnea. The “crescendo-decrescendo”
oscillations of Cheyne-Stokes are most often caused by
hypoxemia and are a frequently encountered symptom
(see Chap. 25) (Fig. 11.2).
Apneusis: is an abnormally patterned breathing
with prolonged inspirations that alternate with short
expiratory movements (Fig. 11.2). Apneustic breathing
is commonly noted after lesions in the pontine
pneumotaxic center discussed below.
Ataxis or ataxic respiration: is an abnormal pattern with
completely irregular breathing and increasing periods
of apnea. As the pattern deteriorates, it may merge with
agonal respiration. It is caused by damage to the medulla
oblongata by stroke or trauma.
Apnea: is the absence of breathing. As generally
used, apnea implies that the cessation is temporary.
A prolonged apnea for any cause is considered
respiratory arrest.
Which spinal cord neurons are most important to respiration? Why? Which neurons innervate the different respiration muscles?
Spinal cord neurons are organized into ventral horn (motor), dorsal horn (sensory), and lateral horn (autonomic) regions. Those in the ventral horn are most critical to respiration, since they include lower motor neurons innervating somatic striated muscles (Fig. 11.3). Major somatic striated muscles involved in respiration include:
Diaphragm: its innervating motoneurons exit at C3-C5
as the phrenic nerve.
Intercostal muscles: innervated by motoneurons within
the thoracic ventral horn with axons that exit the spinal
cord and distribute via the intercostal nerves.
Abdominal muscles: their motoneurons have axons that
track within the lower thoracic and upper lumbar cord
regions.
Accessory muscles: include all muscles that elevate
and splay the ribs, notably the levator costalis, scalene,
transverse thoracic, and sternocleidomastoid.
What are the major muscles involved in innervation that are innervated by craniel nerves? Which nerves are they innervated by and where do these nerves originate?
In addition to its role as the principal area of sensorimotor
integration for respiration, the medulla contains lower motor neurons with fi bers that exit via cranial nerves to innervate striated muscles in the head and neck (Fig 11.4). Motor neurons innervating the tongue muscles are found in the hypoglossal nucleus, while those innervating laryngeal, pharyngeal and facial muscles are found in the ventrolateral medulla. All of these muscles receive rhythmic central nervous system (CNS) motor input during every breath. Major cranial striated muscles that are involved during normal respiration include:
Laryngeal muscles: both laryngeal abductors and
adductors are innervated by motoneurons in the nucleus
ambiguus, whose axons travel with the vagus nerve.
Pharyngeal muscles: also receive motor input from the
nucleus ambiguus by neurons whose axons exit via the
glossopharyngeal and vagus nerves.
Facial muscles: most notably the m. nasalis, by
motoneurons within the facial motor nucleus whose
axons exit via the facial nerve.
Tongue muscles: principally the genioglossus muscle
by motoneurons in the hypoglossal nucleus whose axons
exit via the hypoglossal nerve.
What are the two recognized groups of neurons in the medulla that are involved in the integration and coordination of breathing? Where are they located? What is their function? What are their main components?
Within the medulla are two recognized groups of neurons
involved in the integration and coordination of breathing,
whose functions continue to be intensively investigated. The fi rst of these, the ventral respiratory column, is a longitudinal array of respiratory-related neurons that fi re synchronously with each phrenic nerve discharge. These neurons are found in the ventrolateral reticular formation of the medulla, generally just ventral to the nucleus ambiguus. A subject’s basic respiratory rhythm persists if only these brainstem neurons are intact, albeit poorly controlled. Four main components of the ventral
respiratory column have been identifi ed (Fig. 11.5):
Caudal ventral respiratory group (cVRG): an expiratory area running from the spino-medullary junction to the obex;
Rostral ventral respiratory group (rVRG): the area of
mixed inspiratory and expiratory respiratory neurons just
rostral to the obex;
Pre-Bötzinger Complex: an area of neurons that is
rostral to the rVRG and considered of central importance
for rhythm generation;
Bötzinger Complex: an expiratory area just caudal to
the facial nucleus.
In addition to the ventral respiratory column, a second
brainstem area of importance to respiratory control contains the dorsal respiratory group (DRG), being inspiratory neurons in the ventrolateral part of the nucleus tractus solitarii (NTS) (Fig 11.5).
Describe the important respiratory areas in the pons? What is their function? Where are they located? What happens if they are injured?
Situated rostral to the VRG and DRG neurons of the brainstem,
the pons contains the parabrachial nucleus and the
Kölliker-Fuse area, a neurophil surrounding the brachium
conjunctivum (Fig. 11.6). These two regions contain neurons
considered important as the main “off-switch” for
spontaneous inspiration, and have been called the pontine
pneumotaxic center because lesions here result in apneustic
respiration.
What kind of integration of respiration occurs in the brainstem?
Pontine and medullary respiratory neurons are quite interconnected,
making it diffi cult to assign unambiguous functions
to any particular group of neurons. Investigations of respiratory
control usually are conducted while eliminating variables
that are known to affect the rhythm or pattern of respiration.
This usually means maintaining constant Pao2 or Paco2 levels
in animals that are anesthetized, vagotomized, and sometimes
spinalized. Despite such limitations, it is clear that afferent
inputs from higher brain areas, as well as from chemoreceptors
and mechanoreceptors, converge on this network of brainstem
respiratory neurons (Fig. 11.5). There they produce a pattern of
muscle contractions and thus ventilation that are appropriate for
metabolic needs.
In a comatose patients, describe the breathing patterns that might occur in a patient with an injury to the forebrain, midbrain, rostral pons, and caudal pons/upper medulla.
Respiratory pattern is a key indicator of improper brain
functioning in a comatose patient. During diff use forebrain
depression, as in metabolic encephalopathy with liver
failure, breathing may assume the crescendo-decrescendo
pattern of Cheyne-Stokes respiration, with variable periods
of apnea. Midbrain injury can cause hyperventilation, while
injury to the rostral pons may produce apneusis (Fig. 11.2).
Injury to the lower pons or upper medulla frequently
induces ataxic breathing that often heralds complete
respiratory arrest.
How are rhythm generators in the medulla modulated? Where are these modulators located?
Respiratory rhythm generation is intrinsic to the medulla and
proceeds even without additional sensory input. However,
central respiratory neurons are modulated by afferent inputs affecting the depth, rate, and pattern of respiration. Chemoreceptors
respond to changes in the composition of blood or
other fl uids around them. Major groups of chemoreceptors are
located in the peripheral and central nervous systems.
Where are the peripheral chemoreceptors located? What do they respond to? Where do they send their signals? What do they do? What is their main function? What are some functions for which they are less important?
Peripheral chemoreceptors are located in parenchymal
lobules termed the carotid bodies above the bifurcations
of the common carotid arteries (Fig. 11.7), and the aortic
bodies located along the superior aspect of the aortic arch.
Although the lobules are organized similarly at each location,
the carotid bodies send afferent impulses via the carotid sinus
nerve branch of cranial nerve IX, while the aortic bodies send
signals via cranial nerve X to the NTS in the CNS. In general
terms, these peripheral chemoreceptors respond quickly
to decreasing Pao2 and pHa, and increasing Paco2, with discharge
rates alterable during a single respiratory cycle.
Importantly, they cause all increased ventilation in response
to arterial hypoxemia, although their effect is not appreciable
until Pao2 declines to ~40 mm Hg. Thus, their role in regulating
eupneic breathing is small. It is also thought that their
response to increased Paco2 is less important than that of central
chemoreceptors.
Where are the central chemoreceptors located? What do they respond to? How do they work? What is their response?
The major populations of central chemoreceptors are
located near the ventral surface of the medulla, many near
levels of the exiting hypoglossal nerve (Fig. 11.8). They are
bathed in brain extracellular fl uid (ECF) that rapidly equilibrates
with gaseous CO2 diffusing from blood vessels into
cerebrospinal fl uid (CSF). This local rise in Pco2 acidifi es
CSF and thus stimulates the chemoreceptors, even though
[H+] and [HCO3
–] do not readily cross the blood-brain barrier.
In this manner, a reduction in pHa stimulates ventilation centrally
while an increased pHa is inhibitory (Fig. 11.8).
How does the integration of sensory modulation work?
Systemically the body seldom experiences isolated
hypoxia, hypercapnia, or acidemia. Moreover, the ventilatory
response to a set of variables is greater than the response to
each component, due to integration of these modulatory infl uences
within the CNS.
What are the 3 subtypes of lower airway receptors? Which nerve do they use?
There are several important types of sensory receptors associated
with afferent fi bers in the vagus nerve that respond to
either mechanical or chemical stimulation of the tracheobronchial
tree, including its respiratory mucosa (Table 11.1).
Important subtypes of receptors within the lower airways
and/or the lung parenchyma include three main groups:
Slowly adapting pulmonary stretch receptors (SARs):
Rapidly adapting pulmonary receptors (RARs),
Tracheobronchial C Fibers
