This document discusses control of respiration and drugs affecting it. It describes the local, peripheral and central control of respiration, including chemoreceptors and respiratory centers in the brainstem. It outlines the normal breathing cycle and various reflexes involved, such as chemoreceptor and non-chemical reflexes. Finally, it examines how various drugs can affect respiration, with opioids, benzodiazepines and inhaled anesthetics often depressing it, while doxapram and nicotine can stimulate respiratory drive.

1. Control of Respiration, Reflexes
& Drugs affecting
Dr Bikash Subedi
Moderator : Dr Binod Gautam

2. • respiration: the biochemical process by which
an organism obtains energy
C6H12O6 + 6O2 6CO2 + 6H20
ATP
• Breathing : Process of exchange of gases (O2 &
CO2

3. Control of
respiration
Chemoreceptors
Peripheral
control
Local control
Bronchioles
Alveoli,
capillaries
Central control
Nuclei in Pons &
medulla
cerebral cortex

4. Local control
Lung perfusion
• Vasoconstriction of
the arterioles with
low O2 supply
• Vasodilatation in the
areas of high PaO2
Alveolar ventilation
• Bronchodilation in
areas with high CO2
• Bronchoconstriction
in areas with low CO2

5. Ventilation/perfusion
• Ventilation (V): The amount of O2 reaching alveoli
(litres/min).
• Normal ventilation: 4 litres of air per minute
• Perfusion (Q): The amount of blood flow into the lungs
(litres/min)
• Normal perfusion: 5 litres of blood per minute
• Ventilation/Perfusion ratio: The ratio between the
amount of air entering the alveoli and the amount of
blood draining into the lung. Allows an assessment of
the efficiency of gas exchange.
• common value for ventilation / perfusion is 4/5 or 0.8

6. V/Q
High
V/Q
Q=0
Low
V/Q
V=0
Ventilation exceeds perfusion
Ventilation wasted
Inability to oxygenate
e.g emphysema
SHUNT
no air enters alveoli
Blood remains
de-oxygenated
atelectasis, pneumonia
DEAD SPACE
No perfusion
Eg P.Embolus
POOR VENTILATION
Lack of O2 supply
Asthma, Ch. Bronchitis
pulmonary edema

7. Central control

8. CENTRAL (neural) CONTROL OF
BREATHING
Involuntary
• Located in the medulla &
pons
• directs the depth and rate
of breathing via outputs
from the respiratory centres
• may be modified upon
feedback from other sites
voluntary
• located in the cerebral
cortex
• Sends impulses to the
respiratory motor neurons
via the corticospinal tracts
• Influential factors include
emotion, pain

9. Pre botzinger
complex
located near the upper
end of the medullary
respiratory centre

10. Medullary systems
• Rhythmic respiration generated by pacemaker
cells in pre Bötzinger complex (pre-BÖTC) in
medulla
• Located between nucleus ambiigus and lateral
reticular nucleus

11. Dorsal group of neurons
• Dorsal respiratory group of neurons
(inspiratory)
• Fire in bursts
• Firing leads to contraction of inspiratory
muscles >> inspiration
• When firing stops >>> passive expiration

12. Ventral group of neurons
• Inactive during quite breathing
• Contain both inspiratory/expiratory fibres
• Increased firing of dorsal neurones causes a
spillover
• Then they excite the expiratory muscles >>
ext. Intercostals, abdominal muscles
• Can augment both inspiration & expiration

14. Pontine Respiratory Group
• Pneumotaxic centre
• Impulses from this centre inhibit inspiration
• Promote passive or active exhalation
• Inhibits apneustic centre
• Lesion slower respiration, ↑ tidal vol.

15. Apneustic centre
• Impulses from these neurones excite
inspiratory area of medulla
• Prolongs inspiration
• Receives inhibitory impulse from pneumotaxic
centre
• Inhibitory impulses to expiratory centre

16. Higher centres
• Under voluntary control
• pathways pass from the cerebral cortex to the
motor neurons innervating the respiratory
muscles, bypassing the medullary neurons.
• Affected by emotion, pain

17. Normal breathing cycle
• lasting around 5 seconds
• Inhalation in first 2 seconds followed by 3
seconds of exhalation
• Inhalation: first stage, the DG neurons stimulated
by the apneustic centre, enhance the activities of
the inspiratory muscles
• Exhalation: next 3 seconds, the pneumotaxic
centre inhibits the apneustic centre resulting in
unstimulated DG. These no longer stimulate
inhalation anymore, causing passive exhalation

18. Forced breathing cycle
• cooperation of respiratory centres modified
• Inhalation: both the DRG and inspiratory centres
of the VRG stimulate the contraction of
inspiratory muscles and inhibition of the
expiratory centres of the VG → relaxation of
expiratory muscles, resulting in inhalation
• Exhalation: The DG and inspiratory centres of the
VG inhibited. Expiratory centres of VG stimulate
contraction of expiratory muscles → forced
expiration

19. RESPIRATORY REFLEXES

20. Chemical
• Chemoreceptors
• Changes in PCO2,
pH
mechanical
• mechanoreceptors
Pressure changes
• Baro-receptors
• Carotid sinus
• ↓ BP ↑ R/R

21. Chemoreceptor reflexes
Central
•Located on the
ventrolateral
surface of
medulla
•Stimulated by
changes in pH
and CSF
peripheral
•Located in the
Aortic & Carotid
bodies
•Detect decrease
in PO2 & pH
•Indirect response
to PCO2>> pH

22. Central
Chemoreceptors
↑PCO2, ↑pH
detected in CSF
pH major determinant
CO2+H2O ↔ H++CO3-
Stimulation of DRG
neurons in medulla >>
↑ R/R and CO2
clearance
PCO2 has a potent
acute effect but weak
chronic effect

23. Peripheral
chemoreceptors
•Located in bifurcation of
common carotids and
aortic arch
•Sensitive to PaO2, PaCO2,
pH & perfusion pressure
•Most sensitive to PaO2
•However, significant
effects only when PaO2 <
60mm of Hg

24. Non-chemical reflexes

25. Hering-Breuer reflex
• Produced by stretch receptors in the walls of
bronchi/ bronchioles
• Usually only active at high tidal volumes >
1litre
• function in controlling the inflation and
deflation of the lungs during forced breathing
• volume and stretch of the lungs controlled to
avoid over expansion or over deflation
VGN/DGN – ventral/dorsal group of neurons

26. • Inflation reflex prevents the lungs from
overinflating, regulates tidal volume of the lungs
• When forced inflation → the stretch receptors →
impulse to rhythmicity centres through the vagus
nerve → inhibit the DRG & stimulate the
expiratory centre of the VRG → active exhalation
• DRG/VRG – dorsal/ventral respiratory group

27. Cough reflex
• is a protective reflex against irritants in LRT
deep inspiration
↓
Forced expiration against closed glottis

28. Sneeze reflex
• Similar reflex
• Stimulated by irritants in the upper resp. tract
• Helps to clear the irritants

29. J-receptor reflex
• juxta-pulmonary capillary receptors
• Activated by Inflammation and oedema
• contributes to rapid shallow breathing,
• ↓ tidal volume, ↑ respiratory rate
• Probably related to dyspnea of pulmonary
vascular congestion

30. • Head's paradoxical reflex
• It contradicts the Hering-Breuer inflation reflex in
that inflation is no longer inhibited in the lungs
• Therefore, Head’s paradoxical reflex leads to
irregular deep breaths superimposed on normal
breathing
• It is recognized to be important in the first breath
of babies and also in augmented breaths of
adults (sighs)

31. • Baroreceptor reflexes
• located in the carotid sinus and the aortic arch
mainly responsible for the regulation of blood
pressure
• decrease in intrasinus pressure
→baroreceptor reflex, causing increasing
respiratory rate
• Similarly increased pressure results in
decreased respiratory rate

32. • Muscle spindle reflexes
sensory receptors widely located in the
intercostal muscles
involved in a reflex arc not involving the
medulla (sensory neurons synapse directly
with motor neurons)
• muscle stretching stimulates the contraction
of a large number of intercostal muscles
around the affected muscle spindles

33. • Propioceptor reflex
active and passive movements of joints
stimulate respiration
probably help to increase ventilation during
exercise

34. Drugs affecting respiration

35. Opioids
• Dose-dependent depression of respiration
• Impair response to hypoxia & hypercapnia
• Prolong pauses between breathing
• ↓respiratory rate, compensatory ?↑tidal
volume
• Suppress cough reflex, bronchoconstriction
due to histamine release
• Can be reversed by antagonist- naloxone

36. Benzodiazepines
• Dose- dependent depression of ventilation
• Reduce ventilatory response to hypoxia & hypercapnia
• Synergistic effects with other CNS depressants
(opioids,alcohol)
• COAD patients more susceptible
• Ceiling effect – rarely cause life-threatening resp. depression
unlike opioids
• ↓ Ventilation can be reversed by antagonist- flumazenil.
Effect on PO2, PCO2 may remain
COAD- chronic obstructive airway disease

37. Inhaled anesthetics
• Dose dependent ↑ in frequency of breathing
(except isoflurane)
• Isoflurane ↑ R/R upto 1 MAC. No further
increase
• ↓ tidal volume
• Rapid shallow breathing
• ↑ in R/R insufficient to compensate ↓ tidal
volume. Thus, ↓ minute ventilation

38. Inhaled anesthetics contd..
• Depress ventilatory response to CO2,
N2O causes less of so
• All Profoundly ↓ ventilatory response to
hypoxemia (carotid bodies)
• Halothane, Isoflurane & sevoflurane cause
bronchodilation. helpful COPD patients

39. • Ketamine
causes bronchodilation
airway reflexes intact
↑ bronchial secretions
• Local anesthetics
can depresses hypoxic drive
blunt airway reflexes

40. Respiratory stimulants
DOXAPRAM
• stimulates peripheral chemoreceptors to inc.
respiratory drive
• ↑ ventilatory response to hypoxia &
hypercapnia
• Can double resting minute volume at standard
doses (lower than CNS stimulating doses)
• ?counteracts sedative effects of hypercapnia

41. • Progesterone
probably causes ↑ sensitivity to hypoxia &
hypercapnia
cause of hyperventilation in pregnancy
• Nicotine
in large doses can stimulate peripheral
chemoreceptors

42. references
• NUNN’s applied respiratory physiology
• Guyton & Hall; text-book of medical physiology
• Review of medical physiology; Ganong
• www.fastbleep.com
• Pharmacology & physiology in anesthetic practice ; Robert k.
Stoelting