Control of Respiration – Dr. Lee Siew Keah

Neural Controls of Respiration

• Breathing is regulated by a hierarchy of brain‐stem nuclei that interact continuously with higher brain centres, chemoreceptors, and reflex pathways.

• Medullary Respiratory Centres (located in the reticular formation of the medulla):
• Ventral Respiratory Group (VRG)
• Acts as the rhythm-generating & integrative centre.
• Establishes eupnea – the normal quiet breathing rhythm of $12\text{–}15$ breaths·min⁻¹.
• Inspiratory neurons stimulate the diaphragm via the phrenic nerves and the external intercostal muscles via the intercostal nerves.
• Expiratory neurons reciprocally inhibit inspiratory neurons, shaping the inspiratory–expiratory (I–E) cycle.
• Dorsal Respiratory Group (DRG)
• Receives afferent input from peripheral stretch receptors and chemoreceptors.
• Relays this information to the VRG to fine-tune the basic rhythm.

• Pontine Respiratory Centres (apneustic & pneumotaxic areas):
• “Smooth out” transitions between inspiration and expiration.
• Transmit modifying impulses to the VRG during vocalisation, sleep, or exercise.
• Lesions → apneustic breathing: prolonged inspiratory ‘gasps’ followed by apnoea (≈ $1.5$ breaths·min⁻¹).

• Drug sensitivity: Medullary inspiratory neurons are highly susceptible to CNS depressants (e.g. barbiturates, morphine) → respiratory depression/arrest.

Determinants of Breath Depth & Rate

• Depth – proportional to the degree of stimulation delivered by the respiratory centres to the respiratory muscles.
• Rate – chiefly a function of how long the inspiratory centre remains active.
• Both parameters are continuously modulated to match metabolic demand via:
• Chemical factors (most influential): arterial $P<em>{\text{CO}</em>2}$, $P<em>{\text{O}</em>2}$, and $[H^+]$.
• Neural factors: input from higher centres, reflex arcs, & pulmonary receptors.

Chemical Regulation of Ventilation

1. Arterial $P<em>{\text{CO}</em>2}$ – the Most Potent Driver

• Hypercapnia (↑$P<em>{\text{CO}</em>2}$) ⇒ CO₂ diffuses into CSF → hydrated to carbonic acid $\bigl(\text{CO}<em>2 + \text{H}</em>2\text{O} \leftrightarrow \text{H}<em>2\text{CO}</em>3 \leftrightarrow \text{H}^+ + \text{HCO}<em>3^-\bigr)$ → ↓CSF pH. • Central chemoreceptors (medulla; ≈ $70\%$ of CO₂ response) detect ↑$[H^+]$. • Peripheral chemoreceptors (carotid & aortic bodies; ≈ $30\%$) add to the signal. • Net effect – negative-feedback loop ↑depth & ↑rate → ‘blows off’ CO₂ → arterial $P</em>{\text{CO}_2}$ and pH return to baseline.

2. Arterial $P<em>{\text{O}</em>2}$

• Sensed exclusively by peripheral chemoreceptors.
• A large O₂ reservoir is bound to Hb; therefore ventilation rises only when $P<em>{\text{O}</em>2}$ falls substantially (≈ $\le 60\;\text{mm Hg}$).

3. Arterial pH (non-CO₂ sources)

• Metabolic acidosis – accumulation of lactic acid (vigorous exercise) or keto-acids (poorly controlled DM) – stimulates peripheral chemoreceptors.
• Respiratory centres respond by ↑rate & ↑depth to compensate and raise pH.

Carbonic Acid–Bicarbonate Buffer

• Acts as the major extracellular buffer.
• Excess $H^+$: $\text{HCO}<em>3^- + H^+ \rightarrow \text{H}</em>2\text{CO}<em>3 \rightarrow \text{CO}</em>2 + \text{H}<em>2\text{O}$ → pH rises. • Low $H^+$: $\text{H}</em>2\text{CO}<em>3 \rightarrow \text{HCO}</em>3^- + H^+$ → pH falls back toward normal.
• Slow, shallow breathing → CO₂ retention → ↑$H^+$ → ↓pH.
• Rapid, deep breathing (hyperventilation) → CO₂ washout → ↓$H^+$ → ↑pH (hypocapnia).

Ventilatory Abnormalities & Clinical Correlates

• Hyperventilation
• Depth & rate exceed metabolic CO₂ production.
• Produces hypocapnia → cerebral vasoconstriction → dizziness, fainting.
• First-aid tip – breathing into a paper bag allows rebreathed CO₂ to restore normocapnia.

• Apnoea
• Transient cessation of breathing triggered by excessively low arterial $P<em>{\text{CO}</em>2}$.

• Apneustic Breathing
• Damage to pontine/upper medullary regions → ‘inspiratory cramps’ followed by apnoea; ≈ $1.5$ breaths·min⁻¹.

Neural & Reflex Influences Beyond the Brain Stem

• Hypothalamic Controls
• Strong emotion, pain, or temperature shifts (e.g. fever) modulate breathing via limbic pathways.

• Cortical (Voluntary) Control
• Conscious breath-holding, singing, or playing wind instruments overrides the medullary rhythm until rising CO₂ levels forcibly reinstate automatic breathing.
• Practical example – “drowning vs. death before submersion”: Panic-induced breath-holding ultimately succumbs to CO₂ drive, leading to involuntary respiration under water.

• Pulmonary Irritant Reflexes
• Dust, fumes, mucus, or noxious gases activate irritant receptors → reflex bronchoconstriction, coughing, or sneezing.

• Hering–Breuer (Inflation) Reflex
• Excessive lung inflation stretches pulmonary stretch receptors → vagal afferents terminate inspiration, protecting against over-inflation.

Integrative Summary Diagram (Verbal Description)

• Higher brain centres (cerebral cortex) provide voluntary override (+/–).
• Hypothalamic & limbic inputs relay pain or emotion-linked stimuli (+/–).
• Central chemoreceptors (medulla) monitor CSF pH (linked to CO₂) (+).
• Peripheral chemoreceptors (carotid & aortic bodies) monitor blood $P<em>{\text{O}</em>2}$, $P<em>{\text{CO}</em>2}$, and pH (+).
• Mechanoreceptor pathways (stretch & irritant receptors, muscle/joint proprioceptors) feedback mechanical status (+/–).
• All converge on the medullary & pontine respiratory centres, which in turn drive spinal respiratory motor neurons → respiratory muscles.

Practice-Style Questions Mentioned in Lecture

• “A decrease in pH will have what effect on the respiration rate?”
• Expected reasoning: ↓pH (↑$H^+$) → stimulates peripheral chemoreceptors → ↑respiratory rate & depth.

• “Apneustic breathing occurs as a result of damage to which respiratory centre?”
• Correct answer: Pontine/upper medullary centres (specifically the pontine respiratory group).

Quick Reference of Key Numbers

• Eupnoea: $12\text{–}15$ breaths·min⁻¹.
• Apneustic pattern after pontine damage: ≈ $1.5$ breaths·min⁻¹.
• Peripheral chemoreceptor activation threshold: arterial $P<em>{\text{O}</em>2} \approx 60\;\text{mm Hg}$.
• Central vs peripheral contribution to CO₂ response: $70\%$ vs $30\%$ respectively.