Control of Breathing

Question 1

Medullary respiratory centre (MRC)

Answer 1

is the central integrator for breathing control. It is a system of neurons situated in the brainstem (medulla oblongata and pons).

The medullar respiratory centre consists of a number of groups of neurons, the most important of which are:

(1) Dorsal respiratory group (DRG)
(2) Ventral respiratory group (VRG)

Question 2

Dorsal respiratory group (DRG)

Answer 2

‘Inspiratory centre’. Composed entirely of inspiratory neurons.

Question 3

Ventral respiratory group (VRG)

Answer 3

‘Expiratory’ centre. Composed of inspiratory and expiratory neurons.

Question 4

Quiet breathing

Answer 4

Primarily involves the DRG and rhythm generating neurons in the upper part of the VRG (pre- Botzinger complex).

Efferent signals from the DRG intitiate contraction within the inspiratory muscles, principally the diaphragm (phrenic nerve). Impulses are ramped.

Expiration is passive requiring only the cessation of signals from the DRG and subsequent relaxation of the inspiratory muscle, allowing elastic recoil to occur.

Question 5

Forced breathing

Answer 5

Forced breathing involves the VRG and DRG.

Recruitment of the VRG inspiratory neurons reinforces those of the DRG during forced inspiration.

Expiration entails not only inhibition of all respiratory neurons but also activation of VRG expiratory neurons.

Forced expiration involves contraction of expiratory muscles.

Question 6

Pontine respiratory centre

Answer 6

The pons contains two important control centres that modify the output from the medullary respiratory centre and fine-tune respiratory rhythm.

(1) The pneumotaxic centre in the upper pons determines the length of the inspiratory phase of breathing.
(2) The apneustic centre in the lower pons prolongs inspiratory activity

Question 7

The pneumotaxic centre

Answer 7

In the upper pons, determines the length of the inspiratory phase of breathing.
Increased activity cuts inhibits inspiratory neurons.
Smooth transition for inspiration to expiration.

Question 8

The apneustic centre

Answer 8

In the lower pons, prolongs inspiratory activity.

The pneumotaxic centre usually keeps the apneustic centre suppressed.

Question 9

Factors which alter ventilation

Answer 9

(1) Higher brain centres
(2) Peripheral chemoreceptors (aortic and carotid bodies)
(3) Stretch receptors (Herring-Breuer reflex)
(4) Irritant receptors
(5) Proprioceptors in muscles and joints

Question 10

Medullary respiration centre

Answer 10

The output control automatic breating

Question 11

Cerebral cortex

Answer 11

Exerts voluntary control over breathing (breath holding, hyperventilation, singing, speech)

While the cerebral cortex modifies brainstem control to some degree, it exerts voluntary control of breathing by a separate neural pathway to the respiratory motoneurons (therefore, limited control)

Question 12

Hypothalamus

Answer 12

Emotional stimuli.

Temperature control centres in the hypothalamus also affects the rate of breathing.

Question 13

Thalamus

Answer 13

Areas entrain breathing to body movements e.g. during exercise.

Question 14

Receptors in the airways and lungs

Answer 14

Receptors are located throughout the respiratory tract and lung tissue from the nasal cavity to the alveoli.

(1) Irritant receptors
(2) C-fibre endings
(3) Peripheral sensory receptors in upper airways
(4) Stretch receptors

Question 15

Irritant receptors

Answer 15

Rapidly adapting pulmonary receptors (RARs)

Lie between airway epithelial cells (conducting airways).
Chemoreceptive - mediate the cough reflex/bronchoconstriction

Question 16

C- fibre endings

Answer 16

Located in the pulmonary interstitial space, close to circulation.
Play a role in asthma/allergic reaction.
Sensitive to histamine, prostagandins, bradykinin, smoke, noxious gases, capsaicin.

Question 17

Peripheral sensory receptors in upper airways

Answer 17

Within respirtaory mucosa from nasal cavity to the larynx.

Respond to mechanical and chemical stimuli.

Question 18

Stretch receptors (slowly adapting pulmonary stretch receptors - SARs)

Answer 18

Lie among airway smooth muscle cells.
Mechanoreceptors
Mediate the Hering-Breuer reflex

Question 19

Hering-Breur reflex

Answer 19

When stretch receptors in the small airways and lung tissues are sufficiently stimulated they shorten the inspiratory phase of breathign and inhibit further inflation of the lung.

This reflex only operates in adult humans when tidal volume becomes very high (>1L) e.g. strenuous exercise.

In babies, less than 1 year of age, the H-B reflex is an important determinant of resting tidal volume (chemical drive for breathing is not as sensitive in newborns).

Question 20

Proprioceptors and breathing

Answer 20

Proprioceptors in the form of stretch receptors in muscles and various receptors in joints provide a powerful stimulatory influence to breathing.

These inputs, especially from the limbs and chest wall, become particularly important at the onset of exercise.

Question 21

Chemical control of breathing

Answer 21

Chemoreceptors are among the most important inputs to the brainstem control centres:

(1) Centrally located in the medulla
(2) Periphally located in the aortic and carotid bodies

Question 22

Central chemoreceptors

Answer 22

Detect PCO2 and H+.

They are located near the surface of the ventral medulla (separate from, but close to) the medullary respiratory centre.

These receptors are readily accessible to CO2 which diffuses easily out of the cerebral capillaries into the surrounding tissues and into the CSF.

Ions such as H+ and HCO3- are repelled by the blood brain barrier.

Question 23

Central chemoreceptors: PCO2 and H+

Answer 23

The direct effect of PCO2 on the central chemoreceptors is only transitory. To be fully effective, CO2 must be hydrated in the CSF to yield H+.

Because the CSF has much less protein than plasma it buffers H+ relatively poorly. Therefore, H+ generated from CO2 are able to diffuse to the receptor and intensify the effect.

Question 24

Peripheral chemoreceptors

Answer 24

Peripheral chemoreceptors are located in or close to the wall of major arteries in the neck (carotid bodies) and upper thorax (aortic bodies) and receive a rich blood supply. The largest concentration is in the carotid body.

Each carotid body is innervated by a branch of the carotid sinus nerve, which in turn forms a branch of the glossopharyngeal cranial nerve (IX) which projects to the medulla.

Question 25

Peripheral chemoreceptors and PO2

Answer 25

Carotid body chemoreceptors respond to changes in teh partial pressure of oxygen in arterial blood (PaO2).

There is a small resting discharge from the cartoid bodies via glossopharyngeal nerve to medulla at normal arterial PO2.

When PO2 drops below around 60mmHg, activity sharply increases.

In hyperoxia, the resting nerve discharge is practically silences.

Question 26

Peripheral chemoreceptors

Answer 26

PCO2 and H+.
Peripheral chemoreceptors respond to PCO2 in arterial blood. They respond more rapidly than central chemoreceptors, but overall provide only 25-30% of the total ventilatory response to PCO2.

Unlike the central chemoreceptors, peripheral chemoreceptors respond to changes in arterial [H+]. e.g. keoacidosis.

Question 27

PaCO2 and ventilation

Answer 27

The response to an increase in arterial PCO2 over the range from 35-60 mmHg is linear.

When arterial PCO2 is raised against a background of low arterial PO2, absolute ventilation is increased and there is a significant increase in the slope of the ventilatory response to CO2.

Question 28

What can the ventilatory response to PCO2 be affected by?

Answer 28

(1) Anaesthetics, drugs such as morphine and barbiturates, sleep, aging, chronically elevated PCO2 (e.g. COPD and CO2 retention) - shift response to right and possibly reduce slope of line.)
(2) Hypoxia, neurochemicals and drugs include NE, progesterone and salicylates (shift curve to left and may increase the slope)
(3) In respiratory failure, very high PCO2 may result in CNS narcosis depressing ventilation.

Question 29

Chronic effects of hypercapnia

Answer 29

PCO2 has a great acute stimulatory effect on the respiratory centre.

With chronic exposure to high PCO2, the response gradually declines over 1-2 days to approximately 1/5th its initial effect due to renal compensation with normalise pH

• -> increased excretion of H+
• -> increased reabsorption of HCO3-
• -> increased transport of HCO3- across blood brain barrier to buffer H+

Therefore sensitivity of central chemoreceptors becomes depressed in chronic hypercapnia and response to rises in CO2 is limited (e.g. COPD - increase PCO2 with normal blood pH).

Question 30

The effect of altitude

Answer 30

At altitude PO2 decreases.

• Stimulates hypoxic drive to increase ventilation
• As a result, PaCO2 and H+ will decrease –> decrease ventilation
• The body will adjust over 12-36 hours, increase retention of H+, excretion of HCO3- (kidney)
• As pH is normalised (in arterial blood and CSF), peripheral chemoreceptor stimulation will increase, hypoxic drive is restored. Ventilation will increase (cycle).

Chronic exposure to hypoxia, causes the cells of the carotid bodies to increase in size and sensitivity to the reduced O2 levels

Question 31

Chronic effects of hypercapnia and hypoxia

Answer 31

Patients suffering from chronic disease resulting in both hypercapnia and hypoxia rely less on central chemoreceptors and more on peripheral chemoreceptors than normal.

This has important consequences for teh treatment of these patients especially when it involves oxygen therapy.

• Problem: central chemoreceptors response is blunted - main driver of ventilation is low oxygen. If you give oxygen therapy and correct the decreased PO2, the sitmulus for ventilation is eliminated.
• Also, oxygen therapy may cause greater V/Q inequalities due to release of hypoxic mediated vasocontriction in under-ventilated areas.
• The increas in PaO2 will displace carbon dioxide from haemoglobin (Haldane effect) and increas PCO2.
• Increased PCO2 may lead to acidoses and anaesthetic effect on brain (can give low concentration O2 (24-28%), need to frequently monitor ventilatory state by measuring PCO2).