Determinants of pCO2

  • Terms
    • pCO2 = Arterial Partial Pressure of CO2
    • VCO2 = CO2 Production (normal = 90-130 L/min/m2)
      • Measured using a metabolic cart (measures expired CO2)
    • VE = Minute Ventilation (Respiratory Rate x VT)
    • VD/VT Ratio = Dead Space/Tidal Volume Ratio

Simplified Alveolar Gas Equation

  • Terms
    • PAO2: alveolar PO2 (alveolar oxygen tension)
  • Assumptions
    • FIO2: room air
    • Altitude: sea level
    • Note: arterial PaCO2 (pCO2) is assumed to be nearly the same as alveolar PACO2 in this equation
    • Respiratory Exchange Ratio = 0.8

Inverse Relationship Between Arterial pCO2 and pO2

  • Assumptions
    • A-a gradient remains the same (in this case, A-a gradient = 10)
    • Respiratory Exchange Ratio = 0.8

Increased CO2 Production Results in an Increase in Alveolar Ventilation

  • At a constant alveolar (minute) ventilation, increased CO2 production would thoretically increase the pCO2
    • Normal Patient: increased CO2 production leads to an increase in alveolar (minute) ventilation -> therefore, the patient is able to maintain normal pCO2
    • Patient with Moderate-Severe Lung Disease: patient may be unable to generate an increased alveolar (minute) ventilation to compensate for the increased CO2 production -> pCO2 may rise, possibly resulting in respiratory failure

Alveolar Ventilation is Inversely (But Not Linearly) Related to pCO2 (with varying CO2 production)

  • Patient with Acute/Chronic Hypocapnia: assuming a constant CO2 production (VCO2), a significant increase in minute ventilation (VE) must be present to maintain the low pCO2
    • Example: DKA patient with pH 7.40 and pCO2 30 must maintain a significanty increased VE to maintain the pCO2 at that level -> despite a normal pH, rapid respiratory failure can occur if, for any reason, patient cannot maintain that high VE
  • Patient with Acute/Chronic Hypercapnia: assuming a constant CO2 production (VCO2), a relatively small decrease in VE can produce a significant increase in pCO2
    • Example: chronically hypercapnic COPD with pCO2 60 can experience a significant increase in pCO2 with even a small decrease in VE (due to minimal sedation, etc)

Minute Ventilation (VE) is Inversely (But Not Linearly) Related to pCO2 (with varying VD/VT ratio)

  • Key Point: VD/VT Ratio determines how efficiently the lungs excrete CO2 per breath
  • Assumptions
    • Graph Assumes a Constant CO2 Production (VCO2) of 200 ml/min
    • VCO2 = VA x (PaCO2/PB)
    • VE = VA x 1.21/(1-VD/VT)
  • At Low VD/VT Ratio: a relatively low minute ventilation (VE) must be maintained to keep pCO2 constant at 40
  • At High VD/VT Ratio: a high minute ventilation (VE) must be maintained to keep pCO2 constant at 40
    • If this cannot be maintained, pt will develop hypercapnic respiratory failure

Impact on Shunt Fraction on Arterial pO2 and pCO2

  • Impact of Shunt Fraction on Arterial pO2: pO2 declines linearly with increasing shunt fraction -> the more shunt that exists, the more hypoxemia occurs
  • Impact of Shunt Fraction on Arterial pCO2: pCO2 remains relatively constant over a range of shunt fractions
    • Note: pCO2 only rises after shunt fractions exceeds 50% -> therefore shunt does not typically cause hypercapnia

Etiology of Hypercapnia

  • Respiratory Compensation for Metabolic Alkalosis (see Metabolic Alkalosis, [[Metabolic Alkalosis]])
    • Mechanism: elevated pH results in hypoventilation with a compensatory increase in pCO2
      • However, the degree of hypoventilation is limited by the hypoxic drive to breathe
      • The predicted compensatory increase in pCO2 in response to a primary metabolic alkalosis obeys the acid-base rules: expect 7 increase in pCO2 for each 10 increase in HCO3 or Expected pCO2 = (bicarb x 0.7) + 21 + 1.5
      • Clinical Pearl: ALL cases of subacute or chronic hypercapnia are accompanied by elevated serum bicarbonate (on serum chemistry or ABG)
      • Presence of elevated serum CO2 should raise the suspicion for presence of either a primary metabolic alkalosis OR a primary respiratory acidosis with compensatory metabolic alkalosis
      • Order an ABG to differentiate these conditions
  • Increased CO2 Production: occurs with overfeeding (with tube feedings or TPN)
    • Only causes hypercapnia when alveolar ventilation (VE) is inadequate (ie: in the presence of significant lung disease)
  • Acute Hypoventilation (see Acute Hypoventilation, [[Acute Hypoventilation]]): with acutely decreased VE
  • Chronic Hypoventilation (see Chronic Hypoventilation, [[Chronic Hypoventilation]]): with chronically decreased VE
  • Increased Dead Space Ventilation: with increased VD/VT Ratio
    • Note: hypercapnia only occurs when VD/VT ratio exceeds 50%

Clinical Evaluation of Hypercapnia

  • Increased A-a Gradient
    • Normal VCO2 (Normal CO2 Production)
      • V/Q Mismatch (V/Q ratio >1, dead space ventilation): hypercapnia only occurs when VD/VT ratio >50%
      • COPD: hypercapnia in COPD is multifactorial (due to hypoventilation, V/Q mismatch, etc)
    • Increased VCO2 (Increased CO2 Production): these conditions usually cause hypercapnia only in the setting of underlying lung disease (with inability to excrete CO2)
      • Hypermetabolism
      • Overfeeding: especially wtih excessive carbohydrate, whch generates more CO2 per calorie than do fats
      • Organic Acidosis
  • Normal/Unchanged A-a Gradient (see Acute Hypoventilation, [[Acute Hypoventilation]] and Chronic Hypoventilation, [[Chronic Hypoventilation]])
    • Obstructive PFT’s
      • COPD: hypercapnia in COPD is multifactorial (due to hypoventilation, V/Q mismatch, etc)
    • Restrictive PFT’s + Normal MIP
      • Obesity Hypoventilation Syndrome
      • Obstructive Sleep Apnea
      • Primary Idiopathic Alveolar Hypoventilation Syndrome/Ondine’s Curse
      • Brainstem Disease
      • Pharmacologic Central Respiratory Depressants: opiates, sedatives, etc
    • Restrictive PFT’s + Decreased MIP
      • Motor Neuron Disease
      • Neuropathy
      • Neuromuscular Junction Disease
      • Myopathy
      • Chest Wall Disease

Effects of Hypercapnia

  • Shifts Oxyhemoglobin Dissociation Curve to the Right
    • Decreases Hb affinity for oxygen in the lungs (decreasing loading) and increasing oxygen unloading at the tissues.
  • Decreases Alveolar pO2
  • Both Stimulation and Depression of Cardiovascular System
    • Via competing effects on SVR, CO, etc
    • Usually causes pulmonary hypertension and and increase in CO though
  • Central Nervous System Depression
  • Stimulation of Ventilation
  • Dilation of Vascular Bed
  • Increased Intracranial Pressure (ICP)
  • Anesthesia: seen with pCO2 >200 mm Hg
  • Decreased Renal Blood Flow: seen with pCO2 >150 mmHg
  • Leakage of Intracellular Potassium: seen with pCO2 >150 mmHg
  • Alteration of the Action of Pharmacologic Agents
    • Due to intracellular acidosis, not due to the pCO2 itself


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