Regulation of Respiration

dr. Debby Mirani Lubis

Physiology Department of FK UMSU
 Introduction

Spontaneous
respiration
the
respiratory
rhythmic
muscles
discharge of
nerve motor
impulses neurons
from the
brain
arterial PO2,
PCO2, and H+
concentration
 Neural Control
of Breathing

voluntary control automatic control

pacemaker cells in the

cerebral cortex
medulla

motor neurons motor neurons

motor neurons via the
in the cervical in thoracic
corticospinal tracts
spinal cord spinal cord

diaphragm via the external intercostal

phrenic nerves muscles
 Medullary Systems
• automatic respiration
• Rhythmic respiration is initiated by a small
group of synaptically coupled pacemaker cells
in the pre-Bötzinger complex (pre-BÖTC) on
either side of the medulla between the
nucleus ambiguus and the lateral reticular
nucleus
 Pontine & Vagal Influences
• neurons in the pons and afferents in the vagus
from receptors in the airways and lungs 
modify respiration
• pneumotaxic center An area in the medial
parabrachial and Kölliker–Fuse nuclei of the
dorsolateral pons  contains neurons active
during inspiration and expiration
• The normal function of the pneumotaxic center is
unknown, but it may play a role in switching
between inspiration and expiration
Regulation of Respiratory Activity
 Chemical Control of Breathing
• The receptors in the carotid and aortic bodies
are stimulated by:
1. a rise in the PCO2 or
2. a rise H+ concentration of arterial blood
3. a decline in PO2
Carotid & Aortic Bodies
• carotid body 
near the carotid
bifurcation on
each side 
near a major
arterial
baroreceptor,
the carotid sinus
• two or more
aortic bodies 
near the arch of
the aorta
 Carotid & Aortic Bodies
• Each carotid and aortic body (glomus)
contains islands of two types of cells:
• type I and type II cells,
 surrounded by fenestrated sinusoidal
capillaries
 Type I cells
• The type I or glomus cells are closely associated
with cuplike endings of the afferent nerves
• The glomus cells resemble adrenal chromaffin
cells
• have dense-core granules containing
catecholamines  released upon exposure to
hypoxia and cyanide
• The cells are excited by hypoxia
• the principal transmitter appears to be
dopamine excites the nerve endings by way of
D2 receptors
 The type II cells
• The type II cells are glia-like,
• each surrounds four to six type I cells.
• Their function is probably sustentacular.
• Afferents from the carotid bodies ascend to
the medulla via the carotid sinus and
glossopharyngeal nerves,

• fibers from the aortic bodies ascend in the

vagi
• Type I glomus cells have O2-sensitive K+
channels  conductance is reduced in
proportion to the degree of hypoxia to which
they are exposed
• This reduces the K+ efflux  depolarizing the
cell  causing Ca2+ influx (primarily via L-type
Ca2+ channels) triggers action potentials and
transmitter release  excitation of the
afferent nerve endings
 The receptors are stimulated when:
1. the arterial PO2 is low (because of vascular stasis)
2. the amount of O2 delivered to the receptors per unit
time is decreased.
3. Powerful stimulation is also produced by cyanide,
which prevents O2 utilization at the tissue level.
4. In sufficient doses, nicotine and lobeline activate the
chemoreceptors.
5. infusion of K+ increases the discharge rate in
chemoreceptor afferents, and because the plasma K+
level is increased during exercise, the increase may
contribute to exercise-induced hyperpnea
 Chemoreceptors in the Brain Stem
• The chemoreceptors monitor the H+ concentration of
cerebrospinal fluid (CSF), including the brain interstitial fluid
• CO2 readily penetrates membranes, including the blood–
brain barrier, whereas H+ and HCO3– penetrate slowly.
• The CO2 that enters the brain and CSF is promptly hydrated.
• The H2CO3 dissociates, so that the local H+ concentration
rises.
• The H+ concentration in brain interstitial fluid parallels the
arterial PCO2.
• The magnitude of the stimulation is proportional to the rise
in H+ concentration
• the effects of CO2 on respiration are mainly due to its
movement into the CSF and brain interstitial fluid 
increases the H+ concentration and stimulates receptors
sensitive to H+.
 Ventilatory Responses to Changes in
Acid–Base Balance
• metabolic acidosis : The hyperventilation decreases
alveolar PCO 2 ("blows off CO2") and thus produces a
compensatory fall in blood H+ concentration.
• metabolic alkalosis : ventilation is depressed and the
arterial PCO 2 rises, raising the H+ concentration toward
normal.
• respiratory alkalosis : an increase in ventilation that is
not secondary to a rise in arterial H+ concentration, the
drop in PCO 2 lowers the H+ concentration below
normal
• respiratory acidosis: hypoventilation that is not
secondary to a fall in plasma H+ concentration
 Ventilatory Responses to Co2
• The arterial PCO2 is normally maintained at 40
mm Hg
• arterial PCO2 rises as a result of increased tissue
metabolism
• ventilation is stimulated and the rate of
pulmonary excretion of CO2 increases until the
arterial PCO2 falls to normal, shutting off the
stimulus.
• The operation of this feedback mechanism keeps
CO2 excretion and production in balance
• The resultant accumulation of CO2 in the body
(hypercapnia) depresses the central nervous
system, including the respiratory center, and
produces headache, confusion, and eventually
coma (CO2narcosis).
 Ventilatory Response to Oxygen Lack
• When the O2 content of the inspired air is
decreased, respiratory minute volume is
increased
• any decline in arterial PO2 below 100 mm Hg
produces increased discharge in the nerves
from the carotid and aortic chemoreceptors
 Non-Chemical Influences on
Respiration
• Responses Mediated by Receptors in the
Airways & Lungs
• Receptors in the airways and lungs are
innervated by myelinated and unmyelinated
vagal fibers
• The unmyelinated fibers are C fibers.
• The receptors innervated by myelinated fibers
are commonly divided into slowly adapting
receptors and rapidly adapting receptors
Airway and lung receptor
 Afferents from Proprioceptors
• active and passive movements of joints
stimulate respiration,
• presumably because impulses in afferent
pathways from proprioceptors in muscles,
tendons, and joints stimulate the inspiratory
neurons.
• This effect probably helps increase ventilation
during exercise
 Afferents from "Higher Centers"
• Pain and emotional stimuli affect respiration,
• there must also be afferents from the limbic
system and hypothalamus to the respiratory
neurons in the brain stem.
 Respiratory Components of Visceral
Reflexes
• Inhibition of respiration and closure of the
glottis during :
• vomiting,
• swallowing,
• sneezing