Oxygen delivery and uptake by peripheral tissues: physiology and pathophysiology.
When oxygen availability to tissues becomes limited, several mechanisms interact to maintain a supply-independent O2 uptake by tissues. Among tissues, adrenergic vasoconstriction prevents a vascular steal of a limited O2 supply by tissues with low metabolic demands. Within tissues, increases in perfused capillary density facilitate an increase in the extraction ratio for oxygen ([CaO2-CvO2]/CaO2). Factors that disrupt the physiologic balance between sympathetic-mediated vasoconstriction and local metabolic vasodilation may impair the ability of the organism to adjust the regional extraction of oxygen in response to changes in O2 delivery, resulting in a pathologic dependence of O2 uptake on supply. Patients with ARDS have demonstrated such an O2 extraction defect, although the mechanism is not fully understood. Although a tissue mitochondrial abnormality could explain these findings, experimental studies of endotoxemia and bacteremia demonstrate a peripheral O2 extraction defect similar to that seen in patients. This defect has been found at the whole body level and within intestine, but not within skeletal muscle. Evidence points to a defect in microvascular control as the mechanism responsible for the defect. Other evidence suggests that damaged peripheral endothelial cells may mediate the loss of vascular control. Hence, in patients with ARDS a damaged endothelium in the pulmonary circulation contributes to the lung edemagenesis, and damaged peripheral endothelium may mediate the defect in microvascular control, leading to the pathologic dependence of oxygen uptake on delivery.
Schumacker
P T
PT
Section of Pulmonary and Critical Care Medicine, University of Chicago, Illinois.
Samsel
R W
RW
D004727:Endothelium / Q000648:ultrastructure; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology*; D008928:Mitochondria / Q000648:ultrastructure; D009102:Multiple Organ Failure / Q000503:physiopathology*; D010101:Oxygen Consumption; D012772:Shock, Septic / Q000503:physiopathology