2015A02 Outline the role of carbon dioxide in the maintenance of ventilation.

List:

· Intro

· Sensor

· Controller incl table of modulating factors

· Effector

· Altered response

Intro:

CO₂ homeostasis

· CO₂ produced by Krebs cycle in mitochondrial matrix during aerobic respiration

· 200mL/min, ∝ aerobic metabolic rate

· Excreted by the lungs

· Tight control PaCO₂ at 40mmHg +/-2

· 48mL/100mL arterial, 52/100mL venous

Equation

· PACO₂ = VCO₂ / V_A x k

o Where PACO₂ = PaCO2 if minimal dead space

o And K = 0.863 (from ratio PaCO₂:CaCO₂ at T 37°C)

· Note minute ventilation matched to metabolic rate via control of PaCO₂

· Note negative feedback loop: ↑PaCO₂ -> ↑MV -> ↓ PaCO₂

Sensor:

Peripheral chemoreceptor

· Carotid bodies (via CNIX) > aortic bodies (via CNX)

· Direct sensitivity

· ↑PaCO₂ -> ↓K⁺ efflux -> depolarisation - ↑afferent to resp centre

· Response 5x faster than central. For acute fluctuation

Central chemoreceptor

· Ventral medulla

· Indirect sensitivity (↑PaCO₂ -> ↑pCO₂ in CSF/brain ECF)

· ↓pH -> ↑afferent to resp centre

· Response 4x more powerful than peripheral. Main controller

· ↓Response with time (↑CSF [HCO₃^-] restores pH over ~6 hours)

· ↓Response if chronic hypercapnoea (e.g. severe OHS)

Controller:

Structure

· Respiratory centre in dorsal medulla

· Multiple cell types incl dorsal inspiratory, ventral expiratory, Pre-Botzinger complex pacemaker cells.

Function

· ↑PaCO₂ -> ↑frequency and amplitude of output to respiratory muscle

· ↑2-3L/min minute ventilation for every ↑1mmHg PaCO₂

Effectors:

Primary inspiratory

· Diaphragm via phrenic nerves

· External intercostals via intercostal nerves

· Scalenes via cervical spinal nerves

· Pharyngeal dilators via CNIX and X

Accessory inspiratory

· e.g. sternocleidomastoid

Expiratory (if active)

· Internal intercostals

· Abdominals

Altered response:

	Apnoeic threshold	Slope of sensitivity curve	Reason
Sleep	↑ (mild)	↓ REM only (and mild)
Volatile	↑	↓	? GABA ? glycine ↓sensitivity of glomus cell
Opioid	↑	↓	Mu opioid Inhibit respiratory centre
Propofol	-	↓	?
Benzodiazepine	-	↓
Exercise	↓	-	?
Metabolic acidosis	↓	-	Synergistic effect on glomus cell with PaCO₂
Hypoxia	↓	↑	Synergistic effect on glomus cell with PaCO₂

Feedback welcome at ketaminenightmares@gmail.com