Lecture on Control of Breathing

Introduction

• Focus on control of breathing and chemoreceptors.
• Previous lecture: respiratory centers (medulla, pons) and feedback mechanisms.
• Today's topics: central chemoreceptors and peripheral chemoreceptors.

Central Chemoreceptors

• Importance: Account for 75-80% of ventilation control.
• Location: Bilateral, ventral medulla, surrounded by cerebrospinal fluid (CSF).
• Trigger: Changes in hydrogen ions (pH changes).

Mechanism

• Studies: Early studies used cats to locate respiratory centers.
• pH Changes: Low pH (acidosis) stimulates central chemoreceptors.
• Molecular Activation:
  • Imidazole & Histidine: Two sensor molecules.
  • Hydrogen ions: Bind to imidazole, enable binding with histidine, causing depolarization.
• Role: Important for inspiratory phase, responsible for the "ramp signal" during inspiration.

Physiological Reaction

• Carbon Dioxide Conversion: CO2 crosses blood-brain barrier (BBB), reacts with water in CSF.
• Carbonic Anhydrase: Enzyme catalyzes reaction, producing hydrogen ions leading to pH drop, stimulating chemoreceptors.
• CSF vs Blood: Lack of buffering in CSF makes it sensitive to CO2 changes, unlike blood.

Peripheral Chemoreceptors

• Role: 20-30% response to CO2, 90% response to oxygen changes.
• Location: Bifurcation of the internal and external carotid arteries, and aortic arch.
• Trigger: Mainly hypoxia (low oxygen levels).

Structure

• Carotid Bodies: Small, highly vascularized, oxygen-sensitive.
• Cell Types:
  • Type 1 Cells (Glomus Cells): Sense oxygen changes, produce neurotransmitters (e.g., dopamine).
  • Type 2 Cells: Supportive, form a membrane around type 1 cells.

Mechanism

• Oxygen Sensing:
  • Potassium Channels: Close in response to low oxygen, causing depolarization.
  • Calcium Channels: Open due to depolarization, promote dopamine release.
• Dopamine Release: Stimulates nerves, sends signals to respiratory centers.

Response to Oxygen Levels

• Hypoxia: Increases activity, lowering of PaO2 to ~60 mmHg triggers chemoreceptor response.
• Hyperoxia: Can suppress chemoreceptor activity.

Summary

• Central vs Peripheral Chemoreceptors:
  • Central: Sensitive to CO2/pH, located in medulla.
  • Peripheral: Sensitive to oxygen, located in carotid bodies, aortic arch.
• Peripheral Receptors: Also respond to pH, temperature, chemicals (e.g., nicotine).
• Communication: Signals sent via glossopharyngeal and vagus nerves to respiratory centers.

Conclusion

• Understanding of chemoreceptor roles in breathing regulation.
• Invitation to reach out with questions or for further discussion in office hours.