Pulmonary emphysema and bronchiolar abnormalities are the most characteristic histological lesions in chronic obstructive pulmonary disease (COPD). Hypoxemia and hypercapnia are mainly due to ventilation-perfusion mismatching. Under stable clinical conditions, both intrapulmonary shunt and limitation of oxygen transport from the alveoli to the capillary do not play a critical role in the observed arterial oxygen pressure. During acute exacerbations, ventilation-perfusion inequality worsens, and some cases show mild to moderate shunting. Under these conditions extrapulmonary factors such as breathing pattern, cardiac output, and oxygen uptake have a crucial role in influencing the arterial oxygen pressure.