L32, L33: Control Of Breathing

Question 1

Neural control of breathing

Answer 1

Central Controller
- Motor centre (medulla oblongata)
—> Inspiratory centre
—> Expiratory centre
- Coordinating centre (pons)
—> Pneumotaxic centre (upper pons): promote transition from inspiration to expiration
—> Apneustic centre (middle and lower pons): inhibit transition from inspiration to expiration

Sensors
1. Chemoreceptors: central (medulla), peripheral (aortic and carotid bodies)

2. Nasal and Lung receptors
   - Pulmonary Irritant —> mechanical and chemical irritation in lung + airway diseases —>↑V (but ↓TV)
   - Nasal Irritant (nose, larynx, nasopharynx)—> mechanical and chemical irritant —> sneezing, coughing, bronchoconstriction
   - Stretch —> change in lung volume —> Hering-Breuer reflex
   - Type J receptor (juxta-pulmonary capillary receptor in alveolar wall) —>↑V (but ↓TV) (↑interstitial volume e.g. pulmonary oedema, chemical injury in lung disease)
3. Gamma system
   - Muscle spindles in intercostal muscle and diaphragm
   - muscle elongation in obstructive airway —> ↑muscle contraction
4. Joint and muscle receptor / Ergoreceptor
   - muscle contraction —> ↑V (in exercise)
5. Baroreceptor (carotid sinus, aortic arch, pulmonary artery, great veins)
   - ↑systemic arterial BP —> ↓V
   - ↑pulmonary arterial BP / central venous BP —> ↑V (in heart failure)
6. Thermoreceptor
   - ↑Temp —> ↑V (in fever)

Effectors: respiratory muscle

Neural pathways:

• Vagal feedback (Hering-Breuer reflex)
• Pneumotaxic feedback

Question 2

Factors stimulating peripheral chemoreceptor (aortic and carotid bodies) to ↑V (↑TV, ↑f)

Answer 2

1. ↓PO2
2. ↑PCO2
3. ↓pH
4. ↓blood flow
5. ↑temp
6. drugs

Question 3

Factors stimulating central chemoreceptor (medulla) to ↑V (↑TV, ↑f)

Answer 3

1. ↑PCO2
2. ↓pH
3. ↓blood flow
4. ↑temp
5. drugs

Question 4

Chemical control on breathing

Answer 4

1. PCO2
2. PO2
3. pH

Question 5

Organisation of respiratory centres

Answer 5

Normal inspiration:
Higher centres —>/ - -> Pneumotaxic centre - -> Apneustic centre —> Inspiratory centre (via spinal cord) —> Inspiration

Inspiratory centre and Expiratory centre inhibit each other
Inspiration simulate expiratory centre (stretch receptor)
Expiration stimulate inspiration centre (stretch receptor)

Inspiratory centre (Pneumotaxic feedback) —> Pneumotaxic centre - -> Apneustic centre (less stimulation to inspiration)

Inspiration (Vagal feedback/Hering-Breuer reflex (avoid overstretching of lungs)) - -> Apneustic centre (less stimulation to inspiration)

Inspiration (lung inflation: stretch receptor) —> Expiratory centre —> expiration —> Apneustic centre (via Vagal nerve)(promote inspiration again by making inspiration to expiration transition difficult)

Question 6

CO2 control of breathing

Answer 6

V-PaCO2 relationship

• normal/physiological range (40-60mmHg): rectilinear shape / large response coefficient
• lower range (<40mmHg): parallel to x-axis (V independent of PaCO2: controlled by wakefulness drive)
• higher range (>60mmHg): less steep curve / small response coefficient (CNS depression: V increases only slightly with PaCO2)

Acclimatisation to high PCO2
1. Acute CO2 increase —> increases V (via stimulation of central and peripheral chemoreceptors)
- Peripheral chemoreceptors: Blood (within 1s):
—> ↑CO2 —> ↑H+ —> ↑V (proteins to buffer increase in H+ —> only slight ↑)
- Central chemoreceptors: CSF (20-30s latency response, steady response in 5-10mins):
—> ↑CO2 —> ↑H+ —> ↑↑V (no protein to buffer in CSF —> much larger ↑↑)

2. Chronic PCO2 increase —> gradual decline in ventilators response
   - Excess CO2 —> respiratory acidosis
   - Renal secretion of H+ and reabsorption of HCO3- —> ↑blood [HCO3-]
   - Choroid plexus and brain cells secretion of HCO3- —> ↑CSF [HCO3-]
   - increased [HCO3-] buffer stimulation of H+ on chemoreceptors
   - less/ lost increase in ventilation to CO2 stimulation
   - CO2 no longer a potent ventilatory stimulus
   - reset Central chemoreceptors to higher PCO2 threshold (Peripheral less important)

Question 7

Oxygen control of breathing

Answer 7

V-PaO2 relationship

• Decreasing PaO2 does not stimulate ventilation until <50-60mmHg
• due to sigmoid shape of O2 dissociation curve (>60mmHg: SaO2 is already very high)
• due to braking effects of hypocapnia + alkalosis (↓O2 —> ↑V —> ↓CO2 —> ↓H+ —> ↓V)
• at isocapnia —> much greater ventilation response to O2 lack
• unimportant in physiological control of ventilation

Acclimatisation to low O2
1. Acute O2 drop —> increases V (via stimulation of peripheral chemoreceptors only, central chemoreceptors do not detect PO2 changes)
—> ↓PO2 —> ↑V —> ↓PCO2, ↑blood+CSF pH (act on peripheral and central)
—> (↓V) Braking effect —> only slight ↑V

2. Chronic PO2 decrease —> greater ventilation increase
   - Hypoxia —> induce respiratory alkalosis
   - Renal secretion of HCO3- —> ↓blood [HCO3-]
   - Transport of HCO3- out of CSF —> ↓CSF [HCO3-]
   - decreased [HCO3-] makes PCO2 —> H+ a greater stimulation
   - ventilation response is further increased
   - reset Central chemoreceptors to lower PCO2 threshold
   - O2 lack become an important ventilatory stimulus

Question 8

pH control of breathing

Answer 8

less sensitive to pH change (in metabolic acidosis) than to PCO2 change
—> due to braking effect of hypocapnia:
—> Metabolic acidosis —> ↓pH (non-CO2 acid) —> ↑V —> ↓PCO2 (hypocapnia) —> ↑ blood+CSF pH —> ↓V (Braking effect) —> only slight ↑V
(In respiratory acidosis: PCO2直接升 —> 直接stimulate ventilation)

V-pH relationship

1. ↓pH —> ↑V
   - Respiratory acidosis (hypercapnia): ↑↑V (↑PCO2 —> ↑H+ —> ↑↑V)
   - Metabolic acidosis (compensated hypocapnia): ↑V (↓PCO2 —> ↓H+ —> Braking effect)
2. ↑pH —> ↓V

Question 9

Interactions among PO2, PCO2 and pH on control of breathing

Answer 9

Hypoxia —> increase sensitivity of respiratory system to CO2

Hypercapnia (高PCO2 —> minimise breaking effect due to O2 lack) —> increase sensitivity of respiratory system to O2 lack

Acidosis (less [HCO3-] to buffer) —> decreases CO2 threshold

Question 10

Mechanisms for depressed ventilation in sleep

Answer 10

1. Inhibition of wakefulness drive (wakefulness drive: tonic discharge from ascending reticular formation of brain stem and midbrain)
2. Depressed O2 and CO2 ventilatory response (shift CO2 response curve to right —> ↓V (may go 0: apnea))
3. Depressed tonic activity of upper airway muscle

Question 11

Periodic breathing in light sleep (Non-REM)

Answer 11

Sleep: shift CO2 response curve to right —> ↓V (may go 0: apnea) —> ↑PaCO2 to equilibrium

Arousal: shift CO2 response curve back to left —> ↑V (may go 0: apnea) —> ↓PaCO2 to equilibrium

Question 12

Types of sleep apnea

Answer 12

1. Central apnea (loss of ventilatory effort)
2. Obstructive apnea (upper airway obstruction)
3. Mixed apnea

—> period of apnea (10-90 sec), at least 11 times per sleeping hour
—> normal: <5-10 episodes per sleeping hour

Question 13

Pattern of breathing in wakefulness-sleep states

Answer 13

Awake:

• at rest: regular (wakefulness drive, metabolic control)
• activity: irregular (behaviour control)

Non-REM Sleep:

• light (stage 1+2): periodic (wakefulness, metabolic control)
• heavy (stage 3+4): regular (metabolic control)

REM sleep

• tonic (voluntary muscle inhibition): regular (wakefulness, metabolic control)
• phasic (muscle twitching): irregular (behavioural control)

Question 14

Consequences of sleep apnea

Answer 14

1. Snoring
2. Daytime sleepiness
3. Polycythemia, pulmonary constriction, right heart failure (constant hypoxia state)
4. Systemic hypertension (repeated cerebral sympathetic activation?)