Oxygen Deprivation

Hypoxemia

• Alveolar gas equation
  • predicts the change in PAO₂ that will occur for a given change in PACO₂
  • PAO₂ = alveolar PO₂
  • PIO₂ = PO₂ in inspired air
    • normally, PIO₂ = 150 mm Hg
  • PACO₂ = alveolar PCO₂
  • R = respiratory exchange ratio = (CO₂ production) / (O₂ consumption)
    • normally, R = 0.80
• A-a Gradient
  • alveolar PO₂ (PAO₂) – systemic arterial PO₂ (PaO₂)
  • normal A-a gradient = 15 mm Hg (~Age/4 +4)
    • equilibration of O₂ across alveolar gas and pulmonary capillary blood
      • pulmonary capillary blood becomes systemic arterial blood
    • increases with age
  • hypoxemia → ↑ A-a gradient
    • e.g., shunt, V/Q mismatch, pulmonary fibrosis (diffusion defect)
• Causes of Hypoxemia (↓ PaO₂)
  • High Altitude (normal A-a gradient) 
    • a decrease in barometric pressure (P_B) decreases the PIO₂ of inspired air
      • FiO2 doesn’t change (21%)
      • ↓ P_B → ↓ PIO₂  → ↓ PAO₂ → ↓ PaO₂
  • Hypoventilation (normal A-a gradient)  
    • a decrease in minute ventilation (respiratory rate x tidal volume) decreases PAO₂
      • ↓ ventilation → ↑ PACO₂ → ↓ PAO₂
      • FiO2 and P_B don’t change in alveolar gas equation
  • V/Q Mismatch (↑ A-a gradient)
  • Diffusion Limitation (↑ A-a gradient) 
    • e.g., pulmonary fibrosis
      • ↑ diffusion distance for diffusion
    • e.g., pulmonary edema
      • ↓ surface area for diffusion, ↑ diffusion distance
  • Right-to-Left Shunt (↑ A-a gradient)
• low O₂ shunted blood mixes with and dilutes high O₂ non-shunted blood

Hypoxia

• Decreased Oxygen Delivery to Tissues
  • O₂ content of blood = (O₂ binding capacity) x (% saturation) + dissolved O₂
    • (O₂ binding capacity) x (% saturation) = O₂ bound to hemoglobin
  • O₂ delivery = (cardiac output) x (O₂ content of blood)
• Causes of Hypoxia (↓ O₂ Delivery to Tissues)
  • circulatory (↓ Cardiac Output)
    • ↓ blood flow
  • hypoxemic
    • ↓ PaO₂ → ↓ % saturation → ↓ O₂ content of blood 
  • anemic (see CO poisoning below)
    • ↓ concentration of hemoglobin→ ↓ O₂ content of blood
  • histotoxic (example: cyanide poisoning)
    • ↓ O₂ utilization by tissues (mitochondrial poison)
  • CO Poisoning 
    • ↓ O₂ bound to hemoglobin → ↓ O₂ content of blood, ↓ O₂ delivery to tissues
      • CO binds to hemoglobin with 200x greater affinity than O₂
        • oxygen-hemoglobin dissociation curve left shift 
    • early sign of exposure is headache; significant exposure causes coma, death
    • classical presentation at autopsy is cherry-red appearance of skin
• not common in living patients

Ischemia

• Causes of Ischemia (↓ Blood Flow)
  • ↓ arterial blood flow
    • e.g., atherosclerosis
  • ↓ venous return
    • e.g., Budd-Chiari syndrome