Results from arterial desaturation or presence of an abnormal hemoglobin. Usually evident when arterial saturation is ≤85%, or ≤75% in dark-skinned individuals. Etiologies include:

1. Impaired pulmonary function: Poorly ventilated alveoli or impaired oxygen diffusion; most frequent in pneumonia, pulmonary edema, and chronic obstructive pulmonary disease (COPD); in COPD with cyanosis, secondary polycythemia is often present.
2. Anatomic vascular shunting: Shunting of desaturated venous blood into the arterial circulation may result from congenital heart disease or pulmonary atrioventricular (AV) fistula.
3. Decreased inspired O₂: Cyanosis may develop in ascents to altitudes >4000 m (>13,000 ft).
4. Abnormal hemoglobins: Methemoglobinemia, sulfhemoglobinemia, and mutant hemoglobins with low oxygen affinity (see Chap. 127. Pulmonary Hypertension, HPIM-19).