Hemoglobin (Hb) is a crucial molecule in the human body, consisting of four polypeptide chains, each bound to an iron-containing heme group. This unique structure enables hemoglobin to bind to oxygen, with each molecule capable of combining with four molecules of oxygen, leading to rapid and reversible oxygen loading. When fully loaded with oxygen, it is called oxyhemoglobin, while hemoglobin that has released oxygen is called reduced hemoglobin or deoxyhemoglobin. As hemoglobin binds oxygen, its shape changes, making it more efficient in picking up additional oxygen molecules. This structural adaptation ensures that the process of both oxygen loading and unloading is highly efficient.
The rate at which hemoglobin binds or releases oxygen is finely regulated by several factors, including partial pressure of oxygen (pO2), temperature, blood pH, partial pressure of carbon dioxide (pCO2), and the concentration of 2,3-bisphosphoglycerate (2,3-BPG) in the blood. These factors work together to guarantee adequate oxygen delivery to tissue cells.
Under normal resting conditions, arterial blood hemoglobin is usually 98% saturated with oxygen, and each 100 ml of systemic arterial blood contains about 20 ml of oxygen, expressed as 20 vol% (volume percent) of oxygen content. As blood flows through systemic capillaries, it releases approximately 5 ml of oxygen per 100 ml of blood, resulting in a Hb saturation of 75% and an oxygen content of 15 vol% in venous blood. This means that venous blood still retains a significant reserve of oxygen that can be utilized when needed.
Aside from pO2, other factors such as temperature, blood pH, pCO2, and BPG levels influence hemoglobin saturation at a given PO2. Red blood cells (RBCs) produce 2,3-BPG during glucose metabolism, and their levels increase when oxygen levels are chronically low. These factors can modify hemoglobin's three-dimensional structure, ultimately altering its affinity for oxygen. Increased temperature, pCO2, H+ ions, or 2,3-BPG levels in the blood lowers hemoglobin's affinity for oxygen, facilitating oxygen release. Conversely, decreasing these factors increases hemoglobin's affinity for oxygen.
It's noteworthy that these factors are typically highest in the systemic capillaries, where oxygen unloading is essential. As cells metabolize glucose and consume oxygen, they produce carbon dioxide, raising pCO2 and H+ levels in capillary blood. This weakens the Hb-O2 bond, a phenomenon known as the Bohr effect. Additionally, increased temperature in active tissues reduces hemoglobin's affinity for oxygen, further enhancing oxygen unloading.
