• any level of PO₂ below normal range of 80-90 mm Hg
• All causes of hypoxemia (except shunt) respond to 100% oxygen; V/Q mismatch responds best to small increases in FIO₂.

• (1) Hypoventilation – PCO₂ is inversely related to alveolar ventilation; normal vent/perf (V/Q) = 0.8 - 1.0
• normal PAO₂ = 100; normal PACO₂ = 40
• ß ventilation Þ new steady state of Ý PACO₂ and ß PAO₂ Þ no change in A-a gradient, but ß PaO₂ (arterial hypoxemia)
• changes predicted by PACO₂ equation:
• 
• cannot diagnose hypoventilation if PCO₂ is not elevated
• causes:
• (1) drug intoxications
• (2) CNS disorders
• (3) NM disorders
• (4) chest wall injuries
• (5) COPD
• treatment: Ý FIO₂ – PAO₂ and PaO₂ will recover, but may progress to apnea, so intubation is better
• (2) Shunt – blood passes from right side of heart to left without contacting a ventilated alveolus
• normally, 2-4% of blood bypasses the alveoli via bronchial circulation, etc.
• pathologic shunt occurs with an anatomic shunt – i.e. congenital heart disease, A-V malformations, pulmonary edema, pneumonia, pulmonary embolism; shunted blood mixes with oxygenated blood to lower overall O₂ contentÞ ß PaO₂
• remember difference between CaO₂ and PaO₂: can only average CaO₂
• ß or normal PaCO₂ from Ý ventilation in normal alveoli
• poor response to Ý FIO₂ because of sigmoid dissociation curve; flat in physiologic range
• causes Ý A-a gradient even on 100% oxygen (diagnostic of shunt)
• (3) Ventilation-Perfusion Mismatch – most common cause of hypoxemia
• some exists normally: V/Q = 3.0 in apices ; 0.6 in lower lung (normal V/Q = 0.8 to 1.0)
• V/Q = infinity when no perfusion, zero when no ventilation (shunt) high V/Q = ß PACO₂; low V/Q = hypoxemia
• causes ß PaO₂ due to the low V/Q alveoli; PaCO₂ usually normal
• Ý A-aDO₂ like shunt, but responds well to even small increases in FIO₂, and is completely corrected by 100% O₂
• (4) Diffusion Impairment (rarely the sole cause of hypoxemia)
• inversely proportional to membrane thickness, directly to surface area, diffusion constant, and pressure gradient
• diffusion impairment means it takes longer for capillary PO₂ to come into equilibrium with alveolar PO₂
• normally have 3x the needed contact time for adequate diffusion, but impairment could show up with exercise
• role in hypoxemia is controversial; rarely the cause
• PAO₂ and PaCO₂ are normal; Ý A-aDO₂ responds well to Ý FIO₂
• (5) Breathing a Low PIO₂ – high altitude or a low FIO₂ gas

Summary