CO2 Physiology — PaCO2 Determinants

PaCO₂ is determined by the balance of production and elimination.

CO2 production:

• Normally 200ml/min (compared to average oxygen intake of 250ml/min)
• Byproduct of aerobic metabolism
• Produced in the cell mitochondria via TCA
  • Entry to TCA as acetyl CoA (from CHO, FA, aa)
  • TCA products
    • CO₂
    • Reduced compounds FADH and NADH
    • H⁺ ions
  • 2 molecules of CO₂produced for each 1 molecule of ATP
• Amount of CO2 produce per molecule of substrate varies with the substrate.
  • 1.5 Mole CO₂ per mole of Glucose
  • Respiratory quotient
    • R = CO₂ production / O₂ consumption
    • Depends on fuel substrate
    • 0.7 for fat, 1.0 for CHO
    • 0.8 for typical western diet

CO2 Storage and transport

• ~ 120 litres predominantly as bicarbonate ion
• CO₂ is carried in the blood in 3 forms – bicarbonate (70-80%), carbamino compounds (20-25%), dissolved (5%)
• Bicarbonate:
  • Main form of CO2 delivery in blood
    Via Hendersen-hasselbach:
    CO₂ + H₂O ⇔ H₂CO₃ ⇔ H⁺ + HCO₃^–
• Carbamino compounds:
  • CO₂ combines with terminal amines (mainly Hb) to form carbamic acid dissosciates → at physiological pH to carbamate
• Dissolved:
  • CO₂ ~20 x more soluble than O₂
  • Henry’s law: p=k_Hc (Given a constant temperature, the amount of gas dissolved in a liquid, is proportional to the partial pressure of that gas. where c=solubility of a gas at a fixed temp, k=Henry’s Law (equilibrium) constant p = partial pressure of the gas))
  • thus via Henry’s Law more CO₂ is dissolved

Elimination:

• Small amount dissolved in sweat
• Most via lungs
  • PaCO₂ ~ PACO₂
  • PACO₂ determined by alveolar ventilation equation

Control of Ventilation

Afferents

• Chemoreceptors
  • Central: retrotrapezoidal nucleus – sensitive to changes in CSF [H⁺]
    – ↑CO₂ → ↑[H⁺] → stimulates respiration
  • Peripheral: Aortic bodies (Vagus) and Carotid bodies (Glossopharyngeal)
    – sensitive to PO₂, [H⁺], PCO₂ and blood flow, CO₂
    – ↑CO₂ → ↑ respiration
• Baroreceptors:
  • Aortic arch and carotid sinuses
  • ↓MAP → less stretch → ↑ sympathetic outflow from medullary vasomotor centre → ↑respiration

Pulmonary Receptors

• Stretch receptors:
  • Inflation reflex: ↑stretch inhibits inspiration
  • Deflation reflex: collapse inhibits expiration
• J Fibers:
  • Nociceptive mechano-chemoreceptors
  • On stimulation → Bronchospasm, apnoea, bradycardia and hypotension

Others: Joint and muscle receptors, pain and temperature

Central control of breathing

• Central input: Hypothalamus and cortex (cortex can overrise medulla)
• Controller:
  • Medullary resp centre: Dorsal resp group (Nucleus tractus solitarius – inspiration and timing), Ventral resp group (Pre-botzinger, Botzinger – control of respiration, airway dilatation, central pattern generation)
  • Pontine respiratory group: Pneumotaxic centre (resp rate and pattern of breathing), Apneustic centre (intensity of breathing)
• Efferents:
  • Phrenic nerve – diaphragm
  • Spinal nerves to intercostal muscles
  • Brachial plexus to pec major
  • Accessory muscle to sternocleidomastoid
  • Spinal nerves to abdo muscles

Factors which ↑PaCO₂

• ↑Shunts or ↑V/Q scatter → ↑PaCO₂
• ↑ Alveolar CO₂ → ↑PaCO₂
  • ↑ Production (VCO₂)
    • During vigorous exercise
    • Moderate exercise doesn’t effect pCO₂ and may actually result in ↓pCO₂ due to ↑MV
    • Hypermetabolic states (Sepsis, Fever, MH, neurolept malignant syndrome)
    • Altered (ie pure carb) diet
  • ↑ Barometric pressure/↓Pressure of water
  • ↑ Inspired CO₂
  • Determined predominantly via alveolar ventilation which depends on:
    • Dead space (DS):
      • PE, low CO state, ↑d PEEP → ↑West’s zone     
      • ↑DS → ↓Alveolar Vent → ↑Alveolar CO2 → ↑PaCO2
    • Respiratory Rate: ↓RR → ↓Alveolar Vent → ↑Alveolar CO2 → ↑PaCO2
    • Tidal Volume (Tv): ↓Tv → ↓Alveolar Vent → ↑Alveolar CO2 → ↑PaCO2

Gladwin / Mooney / Sakurai / JC 2020

Answer by Gladwin, JC, Mooney, Sakurai