A group of investigators is researching the changes in oxygen-hemoglobin binding that occur under various clinical conditions. They are especially interested in situations that alter the shape and position of the oxygen-hemoglobin dissociation curve. Which of the following processes would most likely cause a shift from the blue curve to the red curve in the graph below?
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Show Explanatory Sources
The oxygen-hemoglobin dissociation curve describes the relationship between the partial pressure of oxygen (x-axis) and the hemoglobin oxygen saturation (y-axis). Oxygen saturation increases in a sigmoidal fashion as the pO2 increases because of the increase in oxygen-binding affinity that occurs after the first oxygen molecule binds to hemoglobin. As more oxygen molecules bind to hemoglobin, the number of available binding sites decreases and the curve eventually flattens out.
The partial pressure of oxygen in the blood at which hemoglobin is 50% saturated is known as the P50 (dotted black line in diagram above); this value is a standard measure of hemoglobin's affinity for oxygen and is about 26 mm Hg in normal individuals. A leftward shift of the oxygen-hemoglobin dissociation curve occurs when hemoglobin has increased oxygen affinity (ie, a lower P50). Because decreased temperatures help to stabilize the bonds between oxygen and hemoglobin, hypothermia increases hemoglobin's oxygen affinity and shifts the dissociation curve to the left.
(Choice A) 2,3-bisphosphoglycerate (2,3-BPG) concentrations increase in erythrocytes when oxygen availability is reduced, as occurs in chronic lung disease, heart failure, and chronic exposure to high altitudes. Elevated levels of 2,3-BPG decrease hemoglobin O2 affinity (right-shifted curve), allowing release of additional O2 in the peripheral tissues.
(Choices C and D) Anemia severe enough to cause lactic acidosis will result in lower blood pH, shifting the hemoglobin curve to the right. Similarly, hypoventilation causes increased CO2 retention and respiratory acidosis that shifts the curve to the right.
(Choice E) Strenuous exercise will cause increased tissue oxidative phosphorylation, increased tissue CO2 levels, and decreased tissue pH. This results in a shift of the dissociation curve to the right and decreased hemoglobin O2 affinity.
Educational objective:
A left shift of the hemoglobin oxygen dissociation curve indicates increased hemoglobin O2 affinity and can be caused by increased pH, decreased 2,3-bisphosphoglycerate, and decreased temperature. Leftward shifts of the curve inhibit the release of O2 within peripheral tissues.