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



·         Intro

·         Parenchymal effects

·         Neurovascular and pressure effects




·   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


Parenchymal effects:

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/VA 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


Neurovascular and pressure effects:

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




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