Review Question - QID 216579

With higher levels of cellular metabolism (sprinting) and decreased oxygen availability (increased elevation in Colorado), there is decreased hemoglobin affinity for oxygen from increased 2,3-bisphosphoglyceric acid (2,3-BPG).

With oxidative phosphorylation that is critical for normal cellular function, the transport of oxygen is carefully regulated in the body. The oxygen-hemoglobin dissociation curve displays the relationship between the oxygen partial pressure and hemoglobin oxygen saturation. By shifting the curve to the right, there is decreased affinity for oxygen, leading togreater levels of oxygen dissociation for tissue utilization. Factors such as increased carbon dioxide, temperature, increased 2,3-BPG, and decreased pH will lead to a rightward shift. Vice versa, shifting the curve to the left leads to increased affinity for oxygen. Causes include decreased carbon dioxide, temperature, 2,3-BPG, and increased pH. Derived from a glycolysis intermediate, 2,3-BPG is synthesized in states of low oxygen (e.g., increased elevation, airway obstruction, etc.) and stably binds to deoxyhemoglobin. Competition for binding sites leads to decreased oxygen affinity, which ultimately causes increased RBC oxygen release during periods of increased oxygen need.

MacDonald reviews the relationship of 2,3-BPG and oxygen affinity. The quality of stored blood depends heavily on 2,3-BPG, with decreased concentration associated with impairment of oxygen transport. Hypophosphatemia, as seen in postoperative patients, is linked with a reduction in 2,3-BPG concentration. Hence, repletion of inorganic phosphorus in post-operative IV fluids is beneficial.

Incorrect Answers:
Answer 1: Decreased bisphosphoglycerate (BPG) mutase activity would not be expected because the enzyme catalyzes 1,3-BPG to 2,3-BPG. Given the anaerobic metabolic conditions, BPG mutase activity would be expected to increase to respond to greater oxygen needs of the body.

Answer 3: Decreased mitochondria utilization would not be expected. As the patient repeats sprinting, he will use up stored energy (available ATP), other pathways (lactic acid and ATP-phosphocreatine systems), and slowly start utilization of mitochondria for aerobic respiration. Thus, one would expected increased levels of mitochondria utilization.

Answer 4: Decreased reactive oxygen species production would not be expected. ROS are harmful byproducts generated from oxygen metabolism. In order to prevent oxidative damage to DNA and other cellular entities, antioxidants such as glutathione and their maintenance are important. As the patient increases his exercise, there will be higher levels of aerobic respiration and thus additional ROS production.

Answer 5: Increased hemoglobin affinity for oxygen would not be expected given the rightward shift of the oxygen-hemoglobin dissociation curve. For the same partial-pressure of oxygen (not expected to change given the same level of elevation), a rightward shift of the dissociation curve would correspond to a decreased hemoglobin affinity for oxygen.

Bullet Summary:
2,3-BPG is associated with states of low oxygen and leads to a rightward shift of the oxygen-hemoglobin dissociation curve.