Hemoglobin Dissociation, Hemostasis, and EPO Factors

Posted on Mar 17, 2025 in Biology

Hemoglobin Dissociation Curve

The oxygen-hemoglobin dissociation curve is a graphical representation of the progressive increase that occurs in the percentage of hemoglobin combined with O2 as blood O2 partial pressure (PO2) increases. This is referred to as the saturation of Hb.

Blood leaving the lungs has a PO2 of 95 mmHg and a saturation of 97%, while venous blood has a PO2 of 40 mmHg and a saturation of 75%.

Normal human blood contains 15g Hb/100ml of blood, and each gram of Hb can bind 1.34 ml of O2. Therefore, 15g x 1.34 = 20 ml. Thus, 100 ml of blood can combine with 20 ml of O2 when Hb is 100% saturated.

Blood Hb is responsible for stabilizing the partial pressure of O2 in tissues; it has a buffering effect. The normal alveolar PO2 is 104 mmHg. A decline to 60 mmHg results in Hb saturation of 89%, only 8% less than normal (97%). Tissue PO2 changes very little despite substantial falls in alveolar PO2.

Conversely, when alveolar PO2 is raised to 500 mmHg, the maximum O2 saturation of Hb can never climb above 100%, representing an increase of only 3%.

Some factors may shift this curve. It shifts to the right when blood is acidified (pH 7.2), or with increasing CO2 concentration, temperature, or 2,3-DPG levels.

The Bohr effect, shifting the curve to the left, enhances blood oxygenation in the lungs. A rightward shift facilitates the release of O2 from the blood into tissues. The displacement of the curve to the right also occurs during exercise.

The normal blood PCO2 varies between 40 and 45 mmHg, which is a very narrow range. Increased CO2 in the blood causes O2 to move from Hb, which is an important factor in increasing O2 transport. The binding of O2 to Hb tends to drive CO2 from the blood. The more acidic Hb has a propensity to combine with CO2 to form carbaminohemoglobin. Hydrogen ions released by this process join bicarbonate ions to form carbonic acid.

Hemostatic Mechanism

When a blood vessel is injured by mechanical trauma, a process called hemostasis prevents excessive blood loss. It consists of vasoconstriction, platelet aggregation, and blood coagulation.

Coagulation is the process whereby fibrin strands create a network that holds together the components of a blood clot. It is a complex process involving the sequential activation of a number of factors that are present in blood in an inactive form—a cascade of reactions.

There are two pathways that can lead to clot formation. Both are necessary for normal hemostasis.

  • The intrinsic pathway (the slower pathway) is activated as the blood comes into contact with the injured vessel wall. The initial step depends on the Hageman factor (XII). When in contact with blood, it becomes factor XIIa, which subsequently converts factor XI into factor XIa. Factor IX is then converted into factor IXa (Christmas factor) through a Ca2+-dependent process. Factor IXa acts together with platelet factor 3 (PF3) and factor VIII to activate factor X. Activated factor X combines with factor V and PF3 to form a complex that quickly cleaves prothrombin to thrombin.
  • The extrinsic pathway is initiated when blood comes into contact with injured tissue, which releases a protein called tissue factor. Tissue factor combines with factor VII in the presence of Ca2+ and activates factor X. Activated factor X combines with PF3 and factor V to form thrombin from prothrombin.

The end point of both pathways is the conversion of prothrombin into thrombin. Thrombin causes the polymerization of fibrinogen to form fibrin strands, which are insoluble. These strands form a network structure that traps the components of the blood, forming a clot and joining the two edges of the injured vessel.

Factors Necessary for Erythropoietin (EPO) Production

Nutritional Factors

  • Fe2+ (Iron)
  • Folic acid
  • Vitamin B12
  • Vitamin B6

Factors Stimulating EPO Production

  • Anemia
  • Decreased hemoglobin
  • Decreased blood flow
  • Lung disease
  • Decreased blood volume
  • Testosterone
  • Growth hormone (GH)
  • Estrogen
  • Prostaglandins (PGs)
  • Platelet-derived growth factor (PDGF) resulting from the destruction of erythrocytes

Inhibitory Factors

  • Suppressor T cell phenotype