Draft

161  Hypercapnia Pathophysiology

161.1 Summary

  • Pathophysiology of Hypercapnia
  • CO2: Exhaust of Metabolism
  • Why is PaCO2 so tightly controlled?
  • There is no apparent harm from transient CO2 elevation
  • CO2 Kinetics
  • Why does the body use PaCO2 35?
  • Why doesn’t PE cause hypercapnia?
  • Metabolic Parabola
  • How much demand can people handle?
  • The PCO2/Ventilation Response ‘Curve’
  • Measuring Controller Sensitivity
  • Breath Holds

161.2 Slide outline

161.2.1 Slide 1

  • Pathophysiology of Hypercapnia
  • Brian Locke, MD ### Slide 2
  • CO2: Exhaust of Metabolism
  • Aerobic respiration:
  • carbohydrates: C6H12O6 + 6 O2 → 6 CO2 + 6 H2O + 38 ATP
  • RER: VCO2/VO2 6 / 6 1
  • Fat (palmitic acid): C16H32O2 + 23 O2 → 16 CO2 + 16 H2O + 129 ATP
  • RER: VCO2/VO2 16 / 23 ~0.7
  • Glycolysis:
  • Glucose + 2[NAD+] + 2[ADP] + 2[Pi] → 2 Pyruvate + 2[NADH] + 2H+ + 2[ATP] + 2H2O
  • H+ accumulates, H+ + HCO3 → H2CO3 → H2O + CO2
  • RER: VCO2/VO2 1 / 0 ∞, combined with aerobic respiration RER increases. ### Slide 3
  • Why is PaCO2 so tightly controlled?
  • What is a normal PaCO2? 95% of ’normals‘ fall within this range
  • Sea level: 38.3 mmHg, 2 SD (95% CI) +/- 7.5 mmHg. ULN 45 mmHg
  • Elevation (4500 ft): 33.5 mmHg, 42 mmHg is ULN
  • Consider: during exercise there is no change in PaCO2 across a very wide range of VCO2
  • The PaCO2 value is kept with 3 mmHg throughout the Day (Nunn’s) except for transient elevations up to 10 mmHg during REM sleep.
  • The expected PaO2 declines with age (roughly 0.24 mmHg/year), PaCO2 does not change. ### Slide 4
  • There is no apparent harm from transient CO2 elevation
  • Respiratory failure: defined as failure to maintain normal arterial blood gas partial pressures. ### Slide 5
  • CO2 Kinetics
  • VA K VCO2 / PaCO2
  • Alveolar ventilation is proportional to the ratio between CO2 production and the level of CO2 in the blood.
  • VA VE (1- [Vd/Vt])
  • Alveolar ventilation is the minute ventilation minus the fraction of minute ventilation that does not participate in gas-exchange (aka wasted ventilation fraction, or deadspace fraction)
  • PaCO2 K VCO2 / VE (1-[Vd/Vt]) ### Slide 6
  • Why does the body use PaCO2 35?
  • ⬇️ VA K VCO2 / PaCO2 ⬆️
  • The same pH can be achieved at any PaCO2 by adjusting the bicarbonate: pH 6.1 + log [ HCO3 / (0.03 pCO2) ]
  • Ventilation is metabolically expensive
  • work of breathing 2% of O2 at rest
  • increases hugely with exercise or pathology
  • Why doesn’t the body operate with with a PaCO2 of 70? (and an HCO3 of 44 pH 7.42)
  • Davenport Diagram; visualizes Henderson-Hasselbach Relationships ### Slide 7
  • Why doesn’t PE cause hypercapnia?
  • ⬆️ PaCO2 K VCO2 / VE (1-[Vd/Vt ⬆️])
  • PaCO2 changing ALWAYS must indicate either a failure of the control system (won’t breathe), the mechanical systems response to an increase in demand or a constraint (can’t breathe), or both
  • Increase in demand for VE: increase in VCO2, increased in Vd/Vt, (compensation for metabolic acidosis)
  • Constraints: load on respiratory muscles or reduction in their strength ### Slide 8
  • Metabolic Parabola
  • If you hold VCO2 and Vd/Vt constant and plot:
  • PaCO2 K VCO2 / VE (1-[Vd/Vt])
  • Hypothetical move toward a new higher CO2 set-point to reduce work of breathing
  • Controller Response: Hypercapnic Response to Ventilation
  • Hypothetical demand from metabolic acidosis ### Slide 9
  • How much demand can people handle?
  • Back-of-the-envelope math with CPET normal values give a sense
  • Normal 70kg, 60-year-old female VO2 at peak 1.66 L/min (24.5 mL/kg/min)
  • 3.5 mL/min/kg 1 met; thus, normal capacity of 7 Mets
  • Normal ventilatory reserve is 15% or more
  • Thus, normal individuals can tolerate ~8.8-fold increase in VCO2 without a change in PaCO2
  • Equivalent to an 89% Vd/Vt; this is why PE does not cause hypercapnia in the absence of control or mechanical system failure
  • TODO: normal values for MVV? ### Slide 10
  • The PCO2/Ventilation Response ‘Curve’
  • Sensitivity of controller system: force an increase in PaCO2 and observe how much VE increases.
  • Represented by the straight, dashed line
  • Ventilation S (PCO2– B)
  • S is slope (Δ VE / Δ PaCO2)
  • B is the intercept at zero ventilation.
  • Steeper: more sensitive. Flatter: less sensitive
  • Normal range 0.5-8.0 L/min/mmHg (surprisingly wide)
  • 80% of subjects have a response between 1.5 and 5 L/min/mmHg
  • Controller Response: Hypercapnic Response to Ventilation ### Slide 11
  • Measuring Controller Sensitivity ### Slide 12
  • Breath Holds
  • PaCO2 causes an irresistibly strong urge to breathe in individuals with normal respiratory systems
  • on room air, typically near 50 mmHg (diaphragmatic contractions occur at PaCO2 ~46-49)
  • on supplemental oxygen, can tolerate much longer (highly trained apneass can increase their conventional breakpoint to critical hypoxia, which is 20-30 mmHg O2)
  • can be extended by rebreathing gas (the sensation of air hunger is partially mediated by lack of movement in / out) ### Slide 13
  • Things that change controller sensitivity
  • Normal Controller: A
  • Opiate Controller: B (50% reduction in sensitivity)
  • Note: if opiate is administered, apnea can occur due to the absence of ‘hockey stick’ portion
  • Note2: PaCO2 doesn’t change all that much (7mmHg) despite decreased sensitivity (50%) ### Slide 14
  • TODO: No text extracted from this slide. ### Slide 15
  • Can’t Breathe
  • Brain Curve
  • Ve the respiratory controller wants (if mechanical system intact)
  • Ventilation Curve
  • Actual Ve the mechanical system can achieve
  • Dissociation of the curves is air hunger
  • metabolic acidosis and hypoxemia steepens the brain curve slope
  • increased VCO2 and deadspace (metabolic parabola moves up)
  • Decreased compliance flattens ventilation curve
  • B. Pneumonia ### Slide 16
  • How well does nl a-a exchange exclude obstructive lung da?
  • Mechanism of paco2 - not v/q matching bc co2 dissociation is linear so over and under ventilation CAN compensate - unlike V/Q matching’s effect on hypoxemia
  • Additionally, it is directly sensed and thus respiratory compensation occurs

161.3 Learning objectives

  • Pathophysiology of Hypercapnia
  • CO2: Exhaust of Metabolism
  • Why is PaCO2 so tightly controlled?
  • There is no apparent harm from transient CO2 elevation
  • CO2 Kinetics

161.4 Bottom line / summary

  • Pathophysiology of Hypercapnia
  • CO2: Exhaust of Metabolism
  • Why is PaCO2 so tightly controlled?
  • There is no apparent harm from transient CO2 elevation
  • CO2 Kinetics

161.5 Approach

  1. TODO: Outline the initial assessment or decision point.
  2. TODO: Outline the next diagnostic or management step.
  3. TODO: Outline follow-up or escalation criteria.

161.6 Red flags / when to escalate

  • TODO: List red flags that require urgent escalation.

161.7 Common pitfalls

  • TODO: Capture common errors or missed steps.

161.8 References

TODO: Add landmark references or guideline citations.

161.9 Slides and assets

161.10 Source materials