Regulation of Respiration😊

Chemoregulation of Respiration

Types 

Central Chemoreceptors

Location

• Ventral surface of the medulla

Mechanism of Action (MOA)

• ↑ CO2 (blood) → freely crosses BBB

• In CSF:
• CO2 + H2O → H2CO3 (via carbonic anhydrase)
• H2CO3 → H+ + HCO3⁻
• H+ (in CSF) stimulates central chemoreceptors

• Note:
• H+ in blood cannot cross BBB freely

Applied Aspect

Central respiratory depression in COPD

• Central chemoreceptors become insensitive to ↑ PCO2 due to chronic exposure

• Only peripheral chemoreceptors function, driven by hypoxia

• Oxygen therapy contraindicated (c/i):
• Hypoxia is the only remaining respiratory stimulus
• O2 therapy may abolish this → respiratory arrest

Asphyxia

• Involves both central and peripheral chemoreceptors

• Causes:
• ↓ PaO2 (Hypoxia)
• ↑ PCO2 (Hypercarbia)
• ↑ H+ (Acidosis)

• Activates chemoreflex → hyperventilation
• ↑ Rate
• ↑ Depth
• Results in:
• ↓ PCO2
• ↓ H+
• ↑ PO2

Peripheral Chemoreceptors

Location

• Carotid bodies: At carotid bifurcation

• Aortic bodies: Near arch of aorta (usually >2)

• Actual chemoreceptors:
• Type I Glomus cells

• Type II: Glia-like supporting cells

Mechanism

• Glomus cells have oxygen-sensitive K⁺ channels

Stimulated by (in arterial blood)

• ↓ PO₂ (Hypoxia) → Primary/Direct stimulus

• ↑ PCO₂ (Hypercapnea) → Most sensitive

• ↑ H⁺ (Acidosis)

• Hypotension

• Most potent stimulus: Cyanide poisoning (histotoxic hypoxia)

MOA – Glomus Cells

1. ↓ PO₂

2. O₂-sensitive K⁺ channels close

3. Depolarization

4. Ca²⁺ channels open

5. Ca²⁺ influx

6. Dopamine exocytosis

7. Stimulates respiratory centre

• Exocytosis of Dopamine Pathway:
• Both pathways → Stimulate respiratory centre
• via D2 receptors
• Carotid body → Stimulates CN IX
• Aortic body → Stimulates CN X

• Applied Aspect:
• Carotid body transplant
• Has been attempted as a Rx for Parkinson's

Effect of CO2 and O2 on Ventilation

Effect of Carbon Dioxide:

Effect of Oxygen:

PO₂ vs Ventilation Curve

• Non-linear, curved relationship

Mild Hypoxia

• Slow, gradual ↑ in ventilation

• Reason:
• Hypoxia stimulates ventilation
• → CO₂ washout
• → Respiratory alkalosis
• → Alkalosis inhibits ventilation
• → Partial cancellation of hypoxia effect

Severe Hypoxia

• Steep ↑ in ventilation

• Reason:
• Strong hypoxic drive
• Overcomes inhibitory effect of alkalosis

Combined Effect of Hypoxia, Hypercapnia, and Acidosis on Ventilation

Neural Regulation of Respiration

• Voluntary control (conscious breathing):
• By cerebral cortex 

• Automatic control:
• By brainstem centers

Respiratory Centre

• Located in Pons and Medulla.

Pons

Medulla

Dorsal respiratory group (DRG)

• Sensory integration center.

• Receives afferents
• Peripheral chemoreceptors, stretch receptors

• Delivers info to VRG.

Ventral respiratory group (VRG)

• Subdivisions:
• Pre-Bötzinger complex:
• Generates respiratory rhythm (pacemaker).
• Bötzinger complex:
• Active during expiration.
• Caudal VRG:
• Active during forceful expiration
• influences
• accessory muscles,
• abdominal muscles
• external intercostal muscles
• Rostral VRG:
• Dilates airway, larynx, pharynx.

• Mnemonic: Imagine a boat () → moving forward by a special means
• A man stands on back and blows forcefully (Caudal →forceful expiration) → Boat moves forward
• People on front (Rostral/anterior) → Jaw drops (Dilates airway)
• Everyone is in Verge (VRG) of the Bot

Applied Aspects

• Overdrive phenomenon:
• Seen during exercise.
• Requires extra respiratory drive.
• Involves VRG for forceful expiration.

• Odine curse:
• Absence of Pre-Botzinger complex.
• Sleep has intermediate physiological apnea
• Results in no spontaneous breathing during sleep.
• Rx: Mechanical ventilation during sleep.

• Injury between medulla & spinal cord:
• Examples: Direct cervical injury, hanging.
• Causes no spontaneous breathing
• d/t disruption of impulses to diaphragm

Respiratory Pathway

• Initiation:
• Pre-Botzinger complex (in medulla) → phrenic nerve (C3, C4, C5)
• Contracts diaphragm → Initiates inspiration.

• Maintenance:
• Apneustic center → DRG → Ramp signal 
• Smooth sequential ↑ in Tidal volume up to 500ml → Lung stretch 

• Termination:
• Lung stretch (Stretch reflex) → Via vagal afferent → Inhibits Apneustic center.
• Pneumotaxic center → Inhibits Apneustic center.

Hypoxia

• O2 Transport:
1. Dissolved form
2. Hb bound form (Reduced O2 content)

TYPES of Hypoxia

Waveform in Lesions at Respiratory Centers

Pulmonary Reflexes

Altered Breathing Patterns

Normopnoea

• Normal respiration pattern.

Cheyne-Stokes Respiration

• DNA chain like appearance → CCF/Uremia/Brain

• Stroke → but in kidney and heart (CCF, uremia) → go to sleep (sleep)

• Underlying Mechanism:
• Gradual hyperpnea 
• to CO2 washout.
• Gradual hypopnea 
• due to CO2 build up.
• Apnea 

• Seen in:
• Physiologic: Sleep
• Pathologic:
• Congestive Cardiac failure
• Uremia
• Brain disease / injury

Biot's [Ataxic] Breathing

• Irregular pattern
• due to raised ICP.

• hyperpnoea interrupted by sudden apnoea.

• indicates a bad prognosis.

• Seen in:
• Damage to medulla
• meningitis

• Mnemonic: Bite (Biots) Me (Meningitis, Medulla)

• 2 changes → Bi Ots

Kussmaul's Breathing / Acidotic Breathing

• Description: Hyperventilation characterized by:
• Increased rate (↑ Rate)
• Increased depth (↑ depth)

• Seen in:
• Diabetes Ketoacidosis