Classes of tissue hypoxia.

We identify eight causes of tissue hypoxia, falling into three classes, A, B, and C, depending upon the effect on the critical mixed venous pO2 and the optimal oxygen consumption rate. The critical mixed venous pO2 is the value above which the oxygen consumption rate is optimal and independent of the mixed venous pO2 and below which the oxygen consumption rate decreases towards zero. Class A hypoxia: primary decrease in mixed venous pO2. Causes: 1) ischaemic hypoxia (decrease in cardiac output), 2) low-extractivity hypoxia (decrease in oxygen extraction tension, px). Class B hypoxia: primary increase in critical mixed venous pO2. Causes: 1) shunt hypoxia (increased a-v shunting), 2) dysperfusion hypoxia (increased diffusion length from erythrocytes to mitochondria and/or decreased total capillary endothelial diffusion area, e.g., tissue oedema, microembolism), 3) histotoxic hypoxia (inhibition of the cytochrome chain). Class C hypoxia: primary increase in optimal oxygen consumption rate. Causes: 1) uncoupling hypoxia (uncoupling of the ATP formation associated with O2 reduction), 2) hypermetabolic hypoxia (increased energy metabolism, e.g., due to hyperthermia).