Ventilation: Control of Breathing

Question 1

Learning Outcomes

Answer 1

• Describe the location of the primary respiratory centre
• Describe the role of the VRG in the medulla in the neural control of
respiration
• Describe the role of the pons in the neural control of respiration
• Describe the levels at which the basic pattern of neural activity can be altered
• Describe the inputs to the medulla which affect respiration

Question 2

What are the neural and chemical controllers of ventilation

Answer 2

• Alveolar ventilation rate is normally adjusted so that PO2 and PCO2 in the arterial blood are hardly altered even during heavy exercise and other respiratory stresses

• Four major sites responsible for this adjustment:
– Respiratory control centre (source of central pattern generator)
– Central chemoreceptors
– Peripheralchemoreceptors
– Pulmonary mechanoreceptors

Question 3

What nerves innervate the primary muscles of inspiration

Answer 3

Diaphragm - Phrenic nerve

External Intercostal muscles - Intercostal nerves

Question 4

What nerves innervate the secondary muscles of inspiration

Answer 4

Larynx & pharynx - Vagus (CN X) & glossopharyngeal (CN IX) nerves
Tongue - Hypoglossal nerve (CN XII)
Sternocleidomastoids & Trapezius - Accessory nerve (CN XI)
Nares - Facial nerve (CN VII)

Question 5

What nerves innervate the secondary muscles of expiration

Answer 5

Internal Intercostal muscles - Intercostal nerves

Abdominal muscles - Spinal nerves

Question 6

What are respiratory centres?

Answer 6

• Term probably incorrect - it implies there are discrete anatomical regions that can be identified macro- or microscopically
• Better description would be diffuse networks that are active together to bring about the respiratory effect
• ‘Centres’ located in medulla oblongata and pons
• Collect sensory information about O2 and CO2 levels in blood
• Determines signal sent to respiratory muscles which leads to alveolar ventilation

Question 7

Discuss the dorsal respiratory groups

Answer 7

• Most of these neurons are located within the nucleus tractus solitarius
• Receives sensory input from organs of thorax and abdomen
• Neurons in this group emit repetitive bursts of inspiratory neuronal action potentials
• Cause of repetitive bursts not known
• Involves respiratory ramp for 2 seconds
followed by cessation for 3 seconds
• Ramp can be altered by
– Controlling rate of increasing of ramp (heavy breathing, ramp increases rapidly so lungs fill rapidly)
– Controlling limiting point at which ramp suddenly stops (control rate of respiration)

Question 8

Discuss the ventral respiratory groups

Answer 8

There is one

Question 9

Discuss pneumotaxic and bpneustic centres

Answer 9

• Centres modulate, but are not essential for, normal respiratory output
• Pneumotaxic centre located dorsally in nucleus parabrachialis medialis of upper pons
• 1o effect is to control switch-off point of inspiratory ramp (so controls filling phase of lung cycle)
• Strong pneumotaxic signal - inspiration may last for less than 0.5 second while a weak pneumotaxic signal - inspiration may last for 5 or more seconds

Question 10

Discuss chemical control of ventilation

Answer 10

• Ultimate goal of ventilation is to maintain proper levels of PO2, PCO2 & pH (H+)
• Hypercapnia (↑PCO2) and acidosis (↓pH) detected by central respiratory centre
• Hypoxia (↓PO2) detected by peripheral chemoreceptors in carotid and aortic bodies, also detects Hypercapnia (PCO2) and acidosis (pH)

Question 11

Discuss the location of central chemoreceptors

Answer 11

• Exact location of central chemoreceptors is controversial
• Hans Loeschke, Marianne Schlafke and Robert Mitchell identified candidate regions
near ventrolateral medulla
• Applying acid solutions to these areas increased ventilation
• Chemosensitive neurons now also identified bilaterally beneath ventral surface of the medulla and in medullary raphe
• Neurons in these area very sensitive to H+ ions (may be only important direct stimulus)

Question 12

Discuss the mechanism of action of central chemoreceptors

Answer 12

• Chemosensitive area located bilaterally beneath ventral surface of the medulla
• Neurons very sensitive to H+ ions (may be only important direct stimulus)
• H+ ions do not cross blood brain barrier very well, however, CO2 crosses easily
• increase es in blood PCO2 causes PCO2 to increase in interstitial fluid of medulla and CSF
• CO2 combines with H2O to form H+ ions by action of carbonic anhydrase

Question 13

Discuss peripheral chemoreceptor control of respiratory activity in the carotid body

Answer 13

• Carotid bodies & aortic bodies should not be confused with the carotid sinus (baroreceptor) and the baroreceptors of the aortic arch
• How low PO2 excites nerve endings is still largely unknown
• Bodies have multiple highly characteristic glandular-like cells (Glomus cells) that
synapse directly or indirectly with nerve endings
• Both sympathetic & parasympathetic NS innervate carotid body

Question 14

Discuss chemosensitivity of the carotid body

Answer 14

• Senses decreased arterial PO2
– Low PO2, but normal PCO2 and pH
– increase in firing rate of carotid sinus nerve
– At normal values of PCO2 and pH a decrease of PO2 causes progressive increase in firing rate
• Can sense increases in arterial PCO2
– Results show graded increases in PCO2 at a fixed blood pH (7.45) and fixed PO2 (80mmHg), produced graded increases in firing rate of carotid sinus
• Can sense decreases in arterial pH (e.g. metabolic acidosis)
– Blood pH (7.25) and fixed PO2 (80mmHg), firing rate of carotid sinus nerve is greater over all PCO2 values

Question 15

Discuss modulation of respiratory output

Answer 15

Respiratory system receives input from 2 other sources:
– Stretch and chemical/irritant receptors
– Higher CNS centres that control non-respiratory
activity

• Slowly adapting pulmonary stretch receptors
– Hering-Breuer reflex (1868)
– Helps to prevent over-inflation of the lungs
– Stretch receptors located in muscular portions of walls of bronchi and bronchioles
– Send signals thro’ vagal nerves (CNX) to DRG neurons when lungs overstretched
– Feedback response initiated that ‘switches off ‘ inspiratory ramp
– In humans reflex not activated until tidal volume increases to about 3 times normal (i.e. 1.5L / breath)

• Rapidly adapting pulmonary stretch (Irritant) receptors
– Epithelium of trachea, bronchi and bronchioles contains sensory nerve endings, pulmonary irritant receptors
– Responsible for coughing and sneezing

• C-fibre receptors (J Receptors)
– Receptors in alveoli and conducting airways close to
capillaries
– Respond to chemical and mechanical stimuli
– Stimulated during conditions like pulmonary oedema, congestion, pneumonia, Also from endogenous chemicals such as histamine
– Induces shallow breathing, bronchoconstriction & mucus secretion

Question 16

Discuss the cough reflex

Answer 16

• Nerve endings of vagus and/or visceral afferent fibres are activated by irritation of trachea or bronchi
• Action potentials travel to medulla and spinal cord respectively

• Response has 3 phases:
– Preparatory inspiration
– Compressive phase
• Glottis closed by vagal efferent activity
• Forced expiration against a closed glottis
• Pressure increases
– Expulsive phase
• Glottis suddenly opens and trapped air is expelled at high speed by contraction of internal intercostals and abdominal muscles

• Result is to dislodge mucous covering airways and carry irritant away to mouth

Question 17

Discuss higher brain centre activity in the control of breathing

Answer 17

Used for:
• Voluntary Hyperventilation
• Breath-holding
• Speaking
• Singing
• Whistling
• Playing musical wind instruments

Some cortical neurons send axons to respiratory centres in medulla
Some cortical premotor neurons send axons to motor neurons controlling respiratory muscles

Question 17

Discuss higher brain centre activity in the control of breathing

Answer 17

Used for:
• Voluntary Hyperventilation
• Breath-holding
• Speaking
• Singing
• Whistling
• Playing musical wind instruments

Some cortical neurons send axons to respiratory centres in medulla
Some cortical premotor neurons send axons to motor neurons controlling respiratory muscles

Question 18

Discuss normal and abnormal respiratory patterns

Answer 18

• Eupnea – normal breathing
• Sigh - larger than normal breath that occurs at regular intervals in normal subjects
• Inspiratory Apneusis – prolonged inspirations separated by brief expirations
• Vagal breathing – slow, deep inspirations due to vagal interruption
• Cheyne-Stokes respiration – benign respiratory pattern. Cycles of gradual increase in TV, followed by gradual decrease in TV, then apnea – bilateral cortical disease, healthy people at high altitude
• Ataxic breathing – irregular inspirations, separated by long periods of apnea – medullary lesions