Oxygen is essential for human life. Although oxygen dissolves in water, the quantity of dissolved oxygen in blood is insufficient to meet the metabolic demand for oxygen. Hemoglobin is a porphyrin molecule that reversibly binds oxygen and is responsible for the delivery of almost all oxygen to the body. Arterial blood contains high levels of oxygenated hemoglobin that is delivered to the body. Oxygen dissociates from hemoglobin in capillary beds, and venous blood contains much lower levels of oxygen-bound hemoglobin. Venous blood is transported to the lungs, where oxygen uptake occurs to ensure that arterial blood continues to have high levels of oxygen.
The binding of oxygen to hemoglobin is an essential lens through which to view physiological resilience and failure. It also is a lens into the challenge of identifying failure in a clinical setting. The percent of hemoglobin that is bound to oxygen is a nonlinear function of the partial pressure of oxygen. The function is sigmoid-type and called the Hill equation. The sigmoid-type behavior offers resilience: up to a point, large changes in partial pressure of oxygen in the lungs lead to relatively small changes in the percent of available hemoglobin that is bound to oxygen. Beyond that point, however, the percent bound can rapidly decline, putting the entire body at risk for having insufficient oxygen to meet metabolic demand. Mathematically, the transition occurs around a partial pressure of 60 mmHg, corresponding to a percent saturation of 90%. By this reasoning, oxygen-hemoglobin saturation values around 90% are often considered critical cutoffs for escalating care in sick individuals. These cutoffs are satisfying in the sense that they make an appeal to biological mechanism embodied by the Hill equation. However, these cutoffs are often inadequate and based on limited information. The oxygen-hemoglobin dissociation curve itself can be shifted by parameters that we cannot routinely measure (e.g: tissue pH). Oxygen extraction from blood by tissue (as reflected in part by venous saturation) is not routinely measured, as it is invasive. Further the degree to which other physiological sub-systems are compensating can be challenging to define. These themes will be explored in several subsequent chapters.
Michael A. Choma, MD, PhD (Yale University)