The oxyhemoglobin dissociation curve (ODC) is one of the most recognized teachings of basic physiology. It describes the relationship between the saturation of hemoglobin and the partial pressure of arterial oxygen. Intuitively, it makes sense that the more oxygen available (a higher PO2), the more saturated hemoglobin will be (% saturation). But what if the hemoglobin is in a different conformational state because of acidosis or hemoglobinopathy? And once the hemoglobin molecule is saturated with oxygen, how readily will it “give up” the oxygen to end organs and tissues that require it?
Let’s start with the basics. Most adult hemoglobin is hemoglobin A (HbA), an iron-based metalloprotein made of two alpha and two beta globular protein subunits (a tetramer). Each HbA molecule can hold up to four oxygen molecules, but the hemoglobin molecule is also involved in physiologic buffering and carbon dioxide transport (carbaminohemoglobin).
An important teaching point is cooperativity, where when an atom of oxygen binds to hemoglobin, the remaining unoccupied spots on that hemoglobin molecule have an increased affinity for oxygen. In other words, with each oxygen molecule, hemoglobin gets hungrier and hungrier for the next. This positive cooperativity is responsible for the ODC’s sigmoidal shape.
A PO2 of ~27 mmHg in healthy adults corresponds to ~50% hemoglobin saturation (red curve). This is known as the P50 of hemoglobin. Many physiologic stressors can shift the curve rightward or leftward, changing hemoglobin’s P50. It’s important to know what these are and what they mean.
A rightward shift of the ODC (green curve) means that a higher PO2 is required to achieve a similar hemoglobin saturation level compared to the baseline (red curve). This also means that the hemoglobin molecule has LESS affinity for oxygen and is MORE willing to unload oxygen at the tissue level. When considering factors that create a rightward shift, think of a warm exercising muscle with an increased temperature, increased CO2 production (and therefore decreased pH leading to an acidosis), and increased 2,3-diphosphoglycerate (DPG). DPG is a red blood cell metabolite of glycolysis that stabilizes the low-oxygen affinity form of hemoglobin (‘T’) and increases during hypoxia (think high altitude or exercise) and anemia. In these situations, hemoglobin needs to unload oxygen to the starved tissues. Also, sickle cell hemoglobin (HbSS) and sulfhemoglobin cannot readily bind oxygen (low affinity) and are right-shifted.
A leftward shift of the ODC (blue curve) means less PO2 can achieve a higher hemoglobin saturation than the baseline. Hemoglobin has a HIGHER affinity for oxygen and is LESS willing to give up oxygen molecules to peripheral tissues. Many factors that create left shifts (decreased temperature, alkalosis, decreased CO2, decreased DPG) are the opposite of those creating right shifts. Additionally, methemoglobinemia (metHb), a state where the iron moiety in hemoglobin is oxidized to the 3+ state and unable to accept oxygen like the typical 2+ oxidation state, creates a leftward shift. The portion of overall hemoglobin which is metHb has essentially removed binding spots for oxygen. Therefore, oxygen will bind more tightly to the areas it DOES have (higher affinity, left shift). The normal hemoglobin might be fully saturated, but it’s unwilling to give up the oxygen to peripheral tissues, so these patients can appear cyanotic. Similarly, carbon monoxide binds hemoglobin ~250x more readily than oxygen, reducing binding spots for oxygen and shifting the curve leftward. Fetal hemoglobin is structurally different than adult hemoglobin and adapted to have a high affinity for oxygen since the uteroplacental circulation has relatively low partial pressures of oxygen.
This is a fairly simplified overview of the ODC, so drop me a line if you have questions in the comments section below! 🙂