Background

Determinants of pCO2

Terms and Assumptions

• pCO2: arterial partial pressure of carbon dioxide
• k: constant
• VCO2: carbon dioxide production (normal = 90-130 L/min/m2)
  • Measured Using a Metabolic Cart (Which is Capable of Measuring Expired Carbon Dioxide)
• VE: minute ventilation (respiratory rate x tidal volume)
• VD/VT Ratio: dead space/tidal volume ratio

Specific Etiologies of Hypercapnia

• Respiratory Compensation for Metabolic Alkalosis (see Metabolic Alkalosis)
  • Mechanism
    • Elevated pH Results in Hypoventilation with a Compensatory Increase in pCO2
      • However, the Degree of Hypoventilation is Limited by the Hypoxic Respiratory Drive to Breathe
    • The Predicted Compensatory Increase in pCO2 in Response to a Primary Metabolic Alkalosis Obeys the Acid-Base Rules (see Acid-Base)
      • Expect an Increase of 7 in pCO2 for Each Increase of 10 in the HCO3
      • Expected pCO2 = (bicarb x 0.7) + 21 + 1.5
    • Clinical Pearls
      • ALL Cases of Subacute or Chronic Hypercapnia are Accompanied by Elevated Serum Bicarbonate (on Serum Chemistry or Arterial Blood Gas)
      • Presence of Elevated Serum Carbon Dioxide Should Raise the Suspicion for Presence of Either a Primary Metabolic Alkalosis OR a Primary Respiratory Acidosis with Compensatory Metabolic Alkalosis
      • One Would Order an Arterial Blood Gas to Differentiate These Conditions
• Increased Carbon Dioxide Production (VCO2)
  • Occurs with Overfeeding (Generally with Tube Feedings or Total Parenteral Nutrition)
  • Increased Carbon Dioxide Production Only Results in Hypercapnia When Alveolar Ventilation (VE) is Inadequate (ie: in the Presence of Significant Lung Disease, Such as Chronic Obstructive Pulmonary Disease, Acute Respiratory Distress Syndrome, etc)
• Acute Hypoventilation with Acutely Decreased Minute Ventilation (VE) (see Respiratory Failure)
• Chronic Hypoventilation with Chronically Decreased Minute Ventilation (VE) (see Respiratory Failure)
• Increased Dead Space Ventilation with Increased VD/VT Ratio
  • Hypercapnia Only Occurs When the VD/VT Ratio Exceeds 50%

Terms and Assumptions

• PAO2: alveolar partial pressure of oxygen (PO2 or alveolar oxygen tension)
• Respiratory Exchange Ratio: 0.8
• Arterial PaCO2 (pCO2) is Assumed to Be Nearly the Same as Alveolar PACO2 in This Equation
• FIO2 is Assumed to Be Room Air (21% FIO2)
• Altitude is Assumed to Be Sea Level

Terms and Assumptions

• A-a Gradient Remains the Same (in this Case, A-a Gradient = 10)
• Respiratory Exchange Ratio: 0.8

At a Constant Alveolar (Minute) Ventilation, Increased Carbon Dioxide (CO2) Production Should Theoretically Increase the pCO2

• In a Normal Patient
  • Increased Carbon Dioxide (CO2) Production Results in an Increase in Alveolar (Minute) Ventilation, Decreasing the pCO2 Back to a Normal Level (i.e. Approximately 40 mm Hg)
• In a Patient with Moderate-Severe Lung Disease
  • Patient May Be Unable to Increase Their Alveolar (Minute) Ventilation to Compensate for the Increased Carbon Dioxide (CO2) Production
  • Therefor, pCO2 May Increase, Possibly Resulting in Respiratory Failure

Clinical Examples

• In a 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
• In a 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)

Terms and Assumptions

• Graph Assumes a Constant Carbon Dioxide Production (VCO2) of 200 ml/min
• VCO2 = VA x (PaCO2/PB)
• VE = VA x 1.21/(1-VD/VT)

Key Points

• VD/VT Ratio Determines How Efficiently the Lungs Excrete Carbon Dioxide (CO2) Per Breath (i.e How “Sick” the Lungs Are)
  • Low VD/VT Ratio = More Efficient Carbon Dioxide (CO2) Excretion Per Breath
  • High VD/VT Ratio = Less Efficient Carbon Dioxide (CO2) Excretion Per Breath
• At a Low VD/VT Ratio (Healthy Lungs), a Relatively Low Minute Ventilation (VE) is Required to Maintain pCO2 Constant at 40 mm Hg
• At a High VD/VT Ratio (“Sick Lungs”), a High Minute Ventilation (VE) is Required to Maintain pCO2 Constant at 40 mm Hg
  • If This Level of Increased Minute Ventilation Cannot Be Maintained, the Patient Will Develop Hypercapnic Respiratory Failure

Key Points

• pO2 Decreases Linearly and Inversely with Increasing Shunt Fraction
  • The Higher the Degree of Shunt, the Lower the pO2
• In Contrast, pCO2 Remains Relatively Constant Over a Wide Range of Shunt Fractions
  • pCO2 Only Increases After the Shunt Fraction Exceeds 50%
    • For This Reason, Shunt Does Not Typically Result in Hypercapnia

Normal/Unchanged A-a Gradient

• Obstructive PFT’s
  • Chronic Obstructive Pulmonary Disease (COPD) (see Chronic Obstructive Pulmonary Disease): hypercapnia in COPD is multifactorial (due to hypoventilation, V/Q mismatch, etc)
• Restrictive PFT’s + Normal MIP
  • Obesity Hypoventilation Syndrome (OHS) (see Obesity Hypoventilation Syndrome)
    • Obstructive Sleep Apnea (OSA) (see Obstructive Sleep Apnea)
    • Primary Idiopathic Alveolar Hypoventilation Syndrome (Ondine’s Curse) (see Primary Idiopathic Alveolar Hypoventilation Syndrome)
    • Brainstem Disease
    • Pharmacologic Central Respiratory Depressants
  • Opiates (see Opiates)
  • Barbiturates (see Barbiturates)
  • Benzodiazepines (see Benzodiazepines)
  • Propofol (Diprivan) (see Propofol)
• Restrictive PFT’s + Decreased MIP
  • Chest Wall Disease
    • Kyphoscoliosis (see Kyphoscoliosis)
  • Motor Neuron Disease
    • Amyotrophic Lateral Sclerosis (ALS) (see Amyotrophic Lateral Sclerosis)
  • Neuromuscular Junction Disease
    • Myasthenia Gravis (see Myasthenia Gravis)
  • Myopathy
    • Duchenne Muscular Dystrophy (see Duchenne Muscular Dystrophy)
  • Peripheral Neuropathy (see Peripheral Neuropathy)
    • Guillain-Barre Syndrome (see Guillain-Barre Syndrome)

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%
  • Chronic Obstructive Pulmonary Disease (COPD) (see Chronic Obstructive Pulmonary Disease): 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