2009B14 Outline the central nervous system effects on an awake person breathing air containing carbon dioxide.

CO₂

·   Colourless, odourless gas

·   Product of Krebs cycle in mitochondrial matrix, aerobic respiration

Normal CO₂ concentrations

·   Inspired: 0.04% = 0.027mmHg

·   Expired: 4% = 27mmHg

Sequential effects of ↑FiCO₂

↑FiCO₂  ↑PACO₂  ↑PaCO₂  ↑H⁺

1.                               PACO₂ = PiCO₂ + output/alveolar ventilation; hence ↑PiCO₂ -> ↑PACO₂ (alveolar air equation)

2.                               highly lipid soluble, rapid equilibration

3.                               CO₂ + H₂O <-> H₂CO3 <-> H⁺ + HCO₃^-. CO₂ highly lipid soluble; diffuses across BBB, ↑ECF and ICF [H⁺]

↑PACO₂  ↓PAO₂  ↓PaO₂ (and ischaemia)

1.                               PAO₂ = PiO₂ – PaCO₂/0.8 (where PaCO₂ ≈ PACO₂)

2.                               ↓Partial pressure gradient for transfer into pulmonary capillaries

CNS neurons

·   ↑PaCO₂ -> ↑brain ICF [H+]

o PaCO₂ 60-80mmHg: sedation

o PaCO₂ >80mmHg: coma, apnoea

o Normalisation of brain ICF pH occurs over ~6 hours (↑HCO₃^- influx?)

·   ↓PaO₂ -> CNS ischaemia

Chemoreceptors and respiratory centre

·   CO₂ diffuses into central chemoreceptors in ventral medulla -> ↑[H⁺] -> ↑afferent to respiratory centre -> ↑RR, TV

·   CO2 stimulates peripheral chemoreceptors directly

·   MV↑2-3L/min per +1mmHg PaCO₂

·   Normal: ↑MV -> ↓PaCO2 (PaCO2 = VCO₂/V_A x k; PACO₂ = PaCO₂ at equilibrium if minimal shunt)

·   If ↑FiCO₂: ↑MV may not ↓PaCO₂

·   If chronic: ↑CSF or brain ECF [HCO₃^-] -> normalised activity of chemoreceptors

Sympathetic nervous system

·   CO₂ diffuses into neurons -> ↑[H⁺] -> ↑SNS output -> ↑plasma [adrenaline], [noradrenaline]

·   Clinical effects:

o ↑HR, ↑BP ∝ [H⁺]

o Arrhythmias

o Bounding pulse

Sequential neurovascular effects of ↑PaCO₂

↑PaCO₂  ↑Brain ECF/CSF [H⁺]  Vasodilatation  ↓CVR  ↑CBF  ↑CBV  ±↑ICP

1.                               Henderson-Hasselbalch equation: pH = 6.1 + [HCO₃^-]/PaCO₂

a. Note CO₂ can cross BBB, H⁺ can’t

2.                               ↑H⁺ -> ↓activity of L-Ca²⁺ channel, ↑nNOs activity -> ↑NO

3.                               Poiseuille’s law: Resistance = (8 x length x viscosity) / π x radius⁴) note power of 4

4.                               Ohm’s law: CBF = (mAP – CVP or ICP) / CVR

5.                               ↑Vessel radius -> ↑volume

6.                               Monroe-Kellie doctrine: after compensation exhausted, ↑volume one intracranial substance -> ↑↑ intracranial pressure

Effect on CBF

Ratio: +1mmHg ↑PaCO₂ -> +2-3% ↑CBF

(Modified from Miller’s Anaesthesia)

Effect on ICP