Control Of Breathing II: Neural Mechanisms
Control of breathing involves a central pattern generator in the
brain- stem that sets the basic rhythm and pattern of ventilation and controls
the respiratory muscles. It is modulated by higher centres and feedback from sensors,
including chemoreceptors (Chapter 11) and lung mechanoreceptors.
The neural networks involved are complex, reflecting the need to coordinate
ventilation with functions such as coughing, swallowing and vocalization.
Brainstem and central pattern generator The central pattern
generator determines the rate and pattern of breathing, and is a complex
network encompassing diffuse groups of respiratory neurones in the pons and
medulla. These contain inspiratory and expiratory neurones,
with activity corresponding to inspiration and expiration, although others show
more complex relationships. Reciprocal inhibition means activity of
inspiratory neurones inhibits activity of expiratory neurones, and vice versa.
The medulla contains two groups of respiratory neurones. The dorsal
respiratory group (DRG; Fig. 12b) in the nucleus tractus solitarii contains
inspiratory neurones and receives ascending input from central and peripheral
chemoreceptors (Chapter 11; Fig. 12f), and from lung receptors via the vagus
(Fig. 12e). The ventrolateral medulla contains a column of neurones extending
from the lateral reticular nucleus and through the nucleus ambiguus,
comprising the caudal (expiratory neurones) and rostral (inspiratory
neurones) ventral respiratory groups (VRG) and pre-Bo¨tzinger and
Bo¨tzinger complexes (Fig. 12c). Although the
pre-Bo·tzinger complex contains
neurones with intrinsic activity (pacemakers), these may
only be associated with gasping, an autoresuscitative mechanism
following hypoxia, as sectioning between the medulla and pons tends to abolish
eupnoea (normal breathing) and lead to gasping in the absence of vagal input.
Descending output from the medulla regulates activity of respiratory muscle
motor neurones (intercostals, phrenic (diaphragm), abdominal) (Fig. 12d).
The pneumotaxic centre is located in the nucleus parabrachialis
and Ko¨lliker–Fuse nucleus of the pons (Fig. 12a), and has a
critical role in eupnoea and mediating responses to lung receptor stimulation
(see below). It receives ascending input from the VRG, although vagal input
from lung stretch receptors is routed via the DRG. The input from stretch
receptors is important for timing of respiratory rhythm and especially
switching inspiration off as lung volume increases. In the absence of vagal
input, sectioning the mid-pons causes apneusis (prolonged inspiratory
effort with short expirations); it has therefore been suggested that there is
an apneustic centre in the caudal pons, possibly associated with
Ko·lliker-Fuse nucleus. Descending input from the hypothalamus and higher
centres mediates the effects of factors such as emotion and temperature on
breathing, but eupnoea is maintained following sectioning above the pons (Fig.
12), although voluntary control is lost. Voluntary control of breathing is
mediated by motor neurones from the cortex contained in the pyramidal tracts,
which bypass the pneumotaxic and medullary respiratory areas (Fig. 12g).
Certain rare brainstem lesions can leave the voluntary pathways intact while
impairing brainstem mechanisms, so ventilation may cease when the patient falls
asleep (Ondine’s curse; Chapter 44).
The origin of the respiratory rhythm is controversial. Whereas some place this in the VRG and preBo·tzinger
complex, others suggest a switching concept, with eupnoea reflectin the output of a pontomedullary neuronal
circuit that includes pneumotaxic (and apneustic) centres, VRG and DRG. In either case, cycling or switching due to
reciprocal inhibition and 'off switches' within these networks is probably the
source of the rhythm of breathing rather than specifices pacemaker neurones.
Lung receptors and reflexes
Stretch receptors are located in smooth muscle of the bronchial
walls. These are mostly slowly adapting (continue to fir with sustained
stimulation). Their afferent nerves ascend via the vagus. Stimulation of
stretch receptors causes inspiration to be shorter and shallower and delays the
next cycle. These receptors are largely responsible for the Hering Breuer
inspiratory reflex, where lung inflation inhibits inspiratory muscle
activity. Conversely, the deflation reflex augments inspiratory muscle
activity on lung deflation These reflexs are weak during normal breathing in
adults, but become more relevant when tidal volume is large (>1 L,
e.g. in exercise). The reflex is very sensitive in neonates to protect the
lungs against overinflatio due to the highly compliant nature of the chest
wall.
Juxtapulmonary or ‘J’ receptors are located on alveolar and
bronchial walls, close to the capillaries. Their afferents are small un-
myelinated (C-fibre or myelinated nerves in the vagus. Activation causes apnoea
(cessation of breathing) or rapid shallow breathing, falls in heart rate
and blood pressure, laryngeal constriction and relaxation of skeletal muscles.
J receptors are stimulated by increased alveolar wall fluid pulmonary
congestion and oedema, microembolisms and inflammator mediators such as
histamine all of which are associated with lung disease. The general action of
J receptors is depression of somatic and visceral activity, which may be
appropriate for serious lung damage as this would suppress metabolism in the
face of compromised gas exchange.
Irritant receptors are located throughout airways between epithelial
cells, with rapidly adapting afferent myelinated fibre in the vagus. Receptors
in the trachea lead to cough those in lower airways to hyperpnoea. They also
cause reflex bronchial and laryngeal constrictions. Irritant receptors are
stimulated by irritant gases, smoke and dust (Chapters 18 and 33), but also by
rapid large inflation and deflations airway deformation, pulmonary congestion
and inflammation Irritant receptors are responsible for the deep augmented
breaths or sighs seen every 5-20 minutes at rest, which reverse the slow
collapse of the lungs that occurs in quiet breathing. They may be involved with
the firs deep gasps of the newborn ('firs breath') and the Hering-Breuer
deflationar reflex.
Proprioceptors (position/length sensors) are located in the Golgi
tendon organs, muscle spindles and joints of the respiratory muscles, but not
diaphragm. Afferents lead to the spinal cord via dorsal roots, stimulated by
shortening and load in respiratory muscles, although not diaphragm. They are
important for coping with increased load and achieving optimal tidal volume and
frequency. Input from non- respiratory muscles and joints can also stimulate
breathing, for example during exercise.
Other receptors that may modulate respiration:
Pain receptors: stimulation often causes brief apnoea followed by
in- creased breathing.
Receptors in the trigeminal region and larynx: stimulation
may give rise to apnoea or laryngeal spasm.
Arterial baroreceptors: stimulation depresses breathing.
