Dr.Niranjan Murthy H.

L
Asst Professor of Physiology
SSMC, Tumkur
 Introduction
• Spontaneous respiration due rhythmic
discharge of motor neurons
• Center for rhythmic discharge is in
brainstem
• Respiratory center is influenced by higher
centers, reflexes and internal chemical
changes.
 Neural control of breathing
• Voluntary control: located in cerebral
cortex
• Automatic control: pacemaker cells in
medulla
• Final common path: motor neurons of
respiratory muscles
• Reciprocal innervations
 Respiratory center
• Several groups of neurons In pons and
medulla
• Groups:-
(i) Pre-Bötzinger complex
(ii) Dorsal & ventral respiratory group
(iii) Pneumotaxic center
(iv) Apneustic center
Respiratory pattern generator
Pre-Bötzinger complex:
 Small group of coupled pacemaker cells.
 Located between nucleus ambiguus and
lateral reticular nucleus
 Produce rhythmic discharges in phrenic
nerves
 NK1(substance P) & μ-opioid receptors
 5HT4 receptors
 Dorsal respiratory group
• Extends most length of medulla in the
region of NTS
• Receives afferents from airways &
chemoreceptors
• Thought to be respiratory pattern
generator- rhythmic drive to phrenic N
• Primarily ‘I’ neurons
• Lesioning will not abolish automatic
respiratory rhythm
 Ventral respiratory group
• Located anterior and lateral to dorsal
group in nucleus ambiguus & nucleus
retroambiguus.
• (i) Cranial division- innervates accessory
muscles via X N
• (ii) Caudal division- inspiratory &
expiratory drive to intercostal muscles
(‘I’ and ‘E’ neurons with reciprocal
innervation)
• Contribute to extra respiratory drive
Pneumotaxic centre
4 th Ventricle
Apneustic centre
Dorsal respiratory group
Ventral Respiratory group
 Pneumotaxic center
• Medial parabrachial and kölliker-fuse
nuclei of dorsolateral pons
• Normal function is unknown
• Lesioning will prolong respiration and
increase tidal volume
• Limits inspiration
• Inhibit neurons of apneustic center
 Apneustic center
• Present in lower pons
• Activate inspiratory neurons of medulla
• Inhibited by vagal input and pneumotaxic
center
 Experimental inferences
• Sec A & Sec D- respiratory centre
between these sections i.e brain stem
• Sec C- rhythmic respiration with or
without vagus- rhythmically discharging
neurons in medulla; reciprocal
innervation; influence by other parts
• Sec B- apneustic centre in lower pons; it
is inhibited by vagus and pnemotaxic
centre
 Inspiratory ramp signal
• Inspiratory signals are not instantaneous
bursts
• Begins weakly and rises steadily in a ramp
like manner for 2secs.
• Ceases abruptly for next 3secs
• Advantage- causes steady increase in
lung volume
• Pneumotaxic center controls switch-off
point of ramp signal
 VOLUNTARY CONTROL
• Voluntary hyperventilation, breath holding,
etc
• Limited duration
• Via corticospinal tract ending on motor
neurons innervating respiratory muscles
 GENESIS OF RESPIRATION
(+)
Pneumotaxic center

(-)
(-)
Apneustic centre

(-) (+)

‘E’ NEURONS ‘I’ NEURONS

(+)
(-)

XN

Respiratory motor neurons

Intercostal N
Phrenic N
LUNGS
Factors affecting respiratory center
1. Chemical stimuli

2. Non-chemical stimuli
 Chemical regulation
• PaO2, PaCO2 and pH

• Chemoreceptors- central and peripheral

• Pulmonary and myocardial

chemoreceptors
 Respiratory chemoreceptors
Peripheral chemoreceptors- carotid and
aortic bodies:
• Heymans, 1930
 Carotid body
• Located in bifurcation of CCA
• 2mg weight
• 0.04ml/min (2000ml/100gm/min) blood
supply
• Type I and type II cells (glomus cells)
• Sinus nerve (branch of IX N) is sensory
 Stimulus (hypoxia)

O2-sensitive K+ channel inhibited

Reduced K+ efflux

Increased Ca2+ influx

Depolarization

Release of catecholamines

Stimulation of nerve endings via D2 receptors

 Factors stimulating peripheral
chemoreceptors
• Hypoxia
• Vascular stasis
• Asphyxia- lack of O2 and excess of CO2
• Drugs- nicotine, cyanide
• Exercise- increased K+ levels
 Aortic bodies
• Located in arch of aorta
• 2-4 in number
• Aortic nerve, branch of X N
 Central chemoreceptors
• Located 0.2mm from ventral surface of
medulla
• Stimulated by changes in PaCO2
• Stimulation is directly proportional to
change in [H+]
• Present inside blood-brain barrier
• Act via respiratory centers
• The central chemoreceptors regulate the
respiration minute to minute.
• 80-85% of resting respiratory drive is due to
stimulatory effect of CO2 on central
chemoreceptors, while 15-20% of initial drive
is provided by peripheral chemoreceptors.
• Central chemoreceptors are depressed by
hypoxia.
• They are also inhibited by anaesthesia, cyanide
and during sleep.
 Pulmonary and coronary
chemoreceptors
• Bezold-zarisch reflex
• Veratradine, nicotine and other alkaloids
• Bradycardia, hypotension and apnoea
followed by hyperpnoea
 Chemical factors affecting
respiration
I. Effect of PO2
II. Effect of PCO2
• Linear relationship till
a limit
• At 7% of inspired
CO2, alveolar PCO2
approaches that of
PaCO2 and CO2
narcosis sets in.
• Significance: O2-CO2
mixture
• CO2 primarily acts on
central
chemoreceptors
III. Effect of H+ ion concentration:
Acidosis stimulates and alkalosis depresses
respiration
Acts via peripheral chemoreceptors
• Metabolic acidosis-
 diabetes mellitus
 renal failure
 diarrhoea
 starvation
9. Metabolic alkalosis-
 severe vomiting due to GI obstruction
1. Respiratory alkalosis-
 voluntary hyperventilation
 high altitude
4. Respiratory acidosis-
 emphysema
 respiratory depressant drugs
 Interaction of chemical factors
• PAO2 and
PACO2 levels
have additive
effect on
ventilation
 Effect of CO2 on hypoxia & pH

pH 7.3 pH 7.4
100
PAO2 (mm Hg)
20 60 100 20 60
Pulmonary ventilation (l/min)

40

30

20

10
6 ---------------------------------------------------------------
Resting ventilation
0

30 Apnoea point 40
50

Alveolar PCO2 (mm Hg)

Breath Holding: voluntary inhibition.
Breaking point
PaCO2 & PaO2
Breath holding is prolonged by
hyperventilation, breathing 100% O2 or
removing carotid bodies
Effect of hormones:
Ventilation is increased during luteal phase
of menstruation & during pregnancy.
Activation of estrogen-dependent
progesterone receptors in hypothalamus
 Non-chemical regulation
I. Responses mediated by receptors in the
airways & lungs:
 Innervated by vagal fibers
 Hering-Breuer inflation reflex
 Hering-Breuer deflation reflex
 Pulmonary chemoreflex
 Vagal
innervation type location stimulus response

Slowly Airway smooth Lung inflation Shortening of

adapting muscle cells inspiratory time.
Hering-Breuer
reflexes.
Bronchodilation.
Tachycardia.
Myelinated
fibers Rapidly Airway epithelial Lung Hyperpnoea.
adapting cells hyperinflation. Cough.
(irritant Bronchoconstric
receptors) Exogenous & tion.
endogenous subs Mucus
(histamine, PGs) secretion.
Pulmonary C Close to blood Lung Apnea followed
fibers vessels hyperinflation. by rapid
(J receptors) breathing.
Unmyelinated C
fibers Exogenous & Bronchoconstric
endogenous subs tion.
Bronchial C
fibers (bradykinin, Hypotension.
serotonin) Mucus
secretion.
1. Hering-Breuer inflation reflex:
Inflation of lung

Stimulate pulmonary stretch receptors Significance:

Absent at normal
Vagal afferents to apneustic centre
tidal volume.
Threshold at 1-
1.5lts of tidal
Inhibition of apneustic centre volume.

Inhibition of inspiration

Prolonged expiration
2. Hering-Breuer deflation reflex: decrease
in duration of expiration following marked
deflation of lungs.
3. J-reflex:
Hyperinflation of lungs

Juxtacapillary receptors

Pulmonary C fibers

Reflex apnoea,
followed by tachypnoea,
hypotension and bradycardia
J receptors:
• Juxta-pulmonary capillary receptors
• A.S.Paintal, 1955
• May have physiological role in severe
exercise
• Role in pathological conditions like
pulmonary congestion, edema, embolus
and strong irritants.
II. Responses mediated by proprioceptors:
Increase in rate and depth of respiration; during
exercise
III. Responses mediated by irritant receptors:
• Cough reflex- protective; deep inspiration
followed by forced expiration against closed
glottis and sudden opening of glottis
• Sneeze reflex- similar reflex with an open
glottis and expiration through nose
IV. Afferents from baroreceptors:
Inhibit respiration by inhibition of respiratory
centre
Adrenaline Apnoea
V. Afferents from higher centers:
5. Cerebral cortex-
Frontal cortex inhibit respiration.
Motor cortex stimulate respiration.
8. Hypothalamus and limbic system:
Pain, emotional stimuli
Fever
VI. Respiratory components of visceral
reflexes:
• Deglutition reflex- causes apnea by
inhibition of respiratory centre via IX N.
• Hiccup- spasmodic contraction of
diaphragm; closure of glottis during
inspiration
• Yawning- deep inspiration probably to
prevent collapse of alveoli.