Heme is an important functional group of hemoglobin. Bilirubin, which is a byproduct of heme breakdown, comes from red blood cells. The liver receives unconjugated bilirubin from the blood and conjugates it via phase II metabolism to make it more soluble for excretion via the bile and stool. Fat cells (adipocytes), skin cells (epithelial cells), and small intestine absorptive cells (enterocytes) do not contain heme to be processed into bilirubin.

Fetal hemoglobin has a higher affinity for oxygen that adult hemoglobin. Maternal and Fetal blood never mix during pregnancy, but they come close to each other in the placenta.  Oxygen diffuses easily to fetal hemoglobin here. The reason fetal hemoglobin has a higher affinity is it is composed of two alpha and two gamma subunits, while adult hemoglobin is composed of two alpha and two beta subunits.

The Bohr Effect describes hemoglobin's affinty for oxygen as a function of blood pH and carbon dioxide content. An increase in CO₂ concentration will lower the blood pH, causing the hemoglobin affinity for oxygen to reduce. High temperature also causes oxygen to be released from hemoglobin, but is not related to the Bohr Effect.

Think about when you're exercising. Your blood has a reduced O₂ concentration and an elevated CO₂ concentration. These factors allow hemoglobin to release more oxygen in the muscles to faciliate ATP production and maintain energy levels.

Cooperativity, as defined in the passage, requires more than one binding site. Without more than one binding site, it is impossible for a carrier to change its affinity for additional cargo after the first piece is either loaded or unloaded. That additional cargo simply doesn't exist for myoglobin.

All of these gases can be bound by hemoglobin. Hemoglobin transports oxygen from the lungs to the necessary tissue, and carbon dioxide from the tissue to the lungs. Hemoglobin has a much higher affinity for carbon monoxide than oxygen, which is why it is so dangerous to inhale carbon monoxide.

High levels of carbon dioxide (CO₂), low pH, and high temperatures all act to decrease oxygen's affinity toward human hemoglobin. Think of working muscle, which produces hot, acidic, high CO₂ conditions in the blood; in this environment, it is important for hemoglobin to release transported oxygen to provide an aerobic environment to the muscle.

A decrease in pH is generally caused by an increase in carbon dioxide in the blood, and will cause hemoglobin to have a lower affinity to oxygen. This makes sense, because we want to easily release oxygen to tissues with high levels of carbon dioxide, and quickly bind and remove the carbon dioxide from the cells to the lungs for expiration from the body.

Increased temperature will also decrease the affinity of hemoglobin for oxygen.

The oxygen dissociation curve is a graph of hemoglobin saturation versus oxygen partial pressure. As oxygen partial pressure increases, hemoglobin will generally be more saturated. The oxygen partial pressure will affect the saturation percentage of hemoglobin in the blood, but will not shift the curve itself. All other options will shift the oxygen dissociation curve to the right, lowering hemoglobin's affinity for oxygen.

Hemoglobin displays the unique property of cooperativity, meaning that once one molecule of oxygen has bound to the hemoglobin molecule, adding the three next molecules is easier. This gives the hemoglobin binding curve the typical sigmoidal oxygen dissociation curve.

Cooperativity helps hemoglobin bind four oxygen molecules in the lungs and maintain the bonds until it enters a region of very low oxygen partial pressure. The most energy is required to remove the first oxygen; the next three are easier because the cooperativity has been lessened. As hemoglobin travels, it is able to selectively distribute oxygen the areas of the body that need it most because of this property.

Hemoglobin's affinity for oxygen can vary based upon the environment. A right shift, which lowers hemoglobin's affinity for oxygen, occurs when there is a need for oxygen to be released to surrounding tissue. This occurs during exercise, increased temperatures, increased 2,3-bisphosphglycerate, increased carbon dioxide, and decreased pH.

Hyperventilation will increase oxygen and decrease carbon dioxide, which will effectively cause a left shift. Left shifts occur under circumstances opposite from the right shift. A decrease in temperature, 2,3-bisphosphoglycerate, or carbon dioxide will cause a left shift.