Effect of Very High PO2 on Blood Oxygen Transport. When the PO2 in the blood rises above 100 mm Hg, the amount of O2 dissolved in the water of the blood increases markedly. This effect is shown in Figure 1, which depicts the same O2-hemoglobin dissociation curve as that shown in Chapter 41 but with the alveolar PO2 extended to more than 3000 mm Hg. Also depicted by the lowest curve in the figure is the volume of O2 dis solved in the fluid of the blood at each PO2 level. Note that in the normal range of alveolar PO2 (below 120 mm Hg), almost none of the total O2 in the blood is accounted for by dissolved O2, but as the O2 pressure rises into the thousands of millimeters of mercury, a large portion of the total O2 is then dissolved in the water of the blood, in addition to that bound with hemoglobin.
Fig1. Quantity of O2 dissolved in the fluid of the blood and in combination with hemoglobin at very high PO2 values.
Effect of High Alveolar PO2 on Tissue PO2. Let us assume that the PO2 in the lungs is about 3000 mm Hg (4 atmospheres pressure). Referring to Figure 1, one finds that this pressure represents a total O2 content in each 100 milliliters of blood of about 29 volumes percent, as demonstrated by point A in the figure, which means 20 volumes percent bound with hemoglobin and 9 volumes percent dissolved in the blood water. As this blood passes through the tissue capillaries and the tissues use their normal amount of O2, about 5 milliliters from each 100 milliliters of blood, the O2 content upon leaving the tissue capillaries is still 24 volumes percent (point B in the figure). At this point, the PO2 is approximately 1200 mm Hg, which means that O2 is delivered to the tissues at this extremely high pressure instead of at the normal value of 40 mm Hg. Thus, once the alveolar PO2 rises above a critical level, the hemoglobin-O2 buffer mechanism (discussed in Chapter 41) is no longer capable of keeping the tissue PO2 in the normal, safe range between 20 and 60 mm Hg.
Acute Oxygen Poisoning. The extremely high tissue PO2 that occurs when O2 is breathed at a very high alveolar O2 pressure can be detrimental to many of the body’s tissues. For instance, breathing O2 at 4 atmospheres pressure of O2 (PO2 = 3040 mm Hg) will cause brain seizures followed by coma in most people within 30 to 60 minutes. The seizures often occur without warning and, for obvious reasons, are likely to be lethal to divers submerged beneath the sea.
Other symptoms encountered in acute O2 poisoning include nausea, muscle twitchings, dizziness, disturbances of vision, irritability, and disorientation. Exercise greatly increases the diver’s susceptibility to O2 toxicity, causing symptoms to appear much earlier and with far greater severity than in the resting person.
Excessive Intracellular Oxidation as a Cause of Nervous System Oxygen Toxicity—“Oxidizing Free Radicals.” Molecular O2 has little capability of oxidizing other chemical compounds. Instead, it must first be con verted into an “active” form of oxygen. There are several forms of active oxygen, called oxygen free radicals. One of the most important of these is the superoxide free radical O2 −, and another is the peroxide radical in the form of hydrogen peroxide. Even when the tissue PO2 is normal at the level of 40 mm Hg, small amounts of free radicals are continually being formed from the dissolved O2. Fortunately, the tissues also contain multiple enzymes that rapidly remove these free radicals, including peroxidases, catalases, and superoxide dismutases. Therefore, so long as the hemoglobin-O2 buffering mechanism maintains a normal tissue PO2, the oxidizing free radicals are removed rapidly enough that they have little or no effect in the tissues.
Above a critical alveolar PO2 (i.e., above about 2 atmospheres PO2), the hemoglobin-O2 buffering mechanism fails, and the tissue PO2 can then rise to hundreds or thousands of millimeters of mercury. At these high levels, the amounts of oxidizing free radicals literally swamp the enzyme systems designed to remove them, and now they can have serious destructive and even lethal effects on the cells. One of the principal effects is to oxidize the poly unsaturated fatty acids that are essential components of many of the cell membranes. Another effect is to oxidize some of the cellular enzymes, thus damaging severely the cellular metabolic systems. The nervous tissues are especially susceptible because of their high lipid content. Therefore, most of the acute lethal effects of acute O2 toxicity are caused by brain dysfunction.
Chronic Oxygen Poisoning Causes Pulmonary Disability. A person can be exposed to only 1 atmosphere pressure of O2 almost indefinitely without developing the acute oxygen toxicity of the nervous system just described. However, after only about 12 hours of 1 atmosphere O2 exposure, lung passageway congestion, pulmonary edema, and atelectasis caused by damage to the linings of the bronchi and alveoli begin to develop. The reason for this effect in the lungs but not in other tissues is that the air spaces of the lungs are directly exposed to the high O2 pressure, but O2 is delivered to the other body tissues at almost normal Po2 because of the hemoglobin-O2 buffer system.
