Haemoglobin dissociation curve

Haemoglobin dissociation curve

The normal range of haemoglobin in the adult is 12-16gm/100ml blood- expressed as grams percent (gm%). Under normal conditions haemoglobin exists primarily in two forms: oxyhaemoglobin (HBO2) and reduced haemoglobin (Hb). The haemoglobin dissociation curve shows the relationship of plasma oxygen partial pressure to the degree to which potential oxygen carrying haemoglobin sites have oxygen attached (% saturation oxygen). This non-linear relationship accounts for most of the oxygen reserves in the blood. Normally Hb is 50% saturated at plasma PaO2 of 27mmHg. Normal venous blood has an oxygen partial pressure (PvO2) of 40mmHg and an oxyhaemoglobin saturation of 75%. A Pa02 of 60mmHg normally results in approximately 90% saturation. Normal arterial blood has an oxygen partial pressure (Pa02) of 97mmHg and an oxyhaemoglobin saturation of 97%.

The partial pressure of oxygen is critical since it determines the pressure gradient between systemic capillary blood and tissue (as well as between pulmonary capillary blood and alveoli). The quantity of oxygen that may move into (or out of) the blood is dependant upon two factors, the amount of dissolved oxygen and the amount of oxygen carried by the haemoglobin. Under normal conditions the quantity of dissolved oxygen is relatively small compared to the total oxygen carried by the blood. It is important to distinguish the difference between oxygen tension and oxygen content. Oxygen content represents the sum total of the oxygen attached to the haemoglobin and that in the plasma.

Haemoglobin has a strong affinity for oxygen. It is this property of haemoglobin that allows poorly oxygenated blood to oxygenate readily in the pulmonary capillary bed. On the other hand this affinity for oxygen may make haemoglobin less able to release oxygen at tissue level. Certain factors in the blood alter the affinity and in doing so change the normal relationship between haemoglobin saturation and oxygen tension. In other words, a change in the haemoglobin affinity for oxygen changes the position of the haemoglobin dissociation curve.

A decrease in the oxygen affinity results in a shift of the oxygen curve to the right. A shift to the right aids oxygen movement from the blood to the tissue in the peripheral capillaries. However an extreme shift to the right always results in decreased oxygen content limiting the amount of the oxygen that may be given to the tissues regardless of how easily it can dissociate from the haemoglobin. This shift to the right is the result of acidemia (increased H+), hyperthermia (fever), hypercarbia (increased PaCo2) and increased BPG (formerly called 2,3-DPG). An increased oxygen affinity results in a shift of the oxygen dissociation curve to the left.

Physiological factors such as changes in hydrogen ion concentration, carbon dioxide tension, and temperature affect haemoglobin affinity for oxygen. The greater the haemoglobin affinity for oxygen, the less potential effectiveness any arterial oxygen tensions has in delivering oxygen to the tissues.

Haemoglobin and other factors

Although PO2 is the most important factor in determining the percent of O2 saturation of haemoglobin, several other factors influence the tightness or affinity with which haemoglobin binds O2.

These will shift the entire curve to the left (higher affinity) or to the right (lower affinity), which show how the homeostatic mechanisms adjust body activities to cellular needs.

· Acidity (pH). As acidity increases (pH decreases), the affinity of haemoglobin for O2 decreases and O2 dissociates more readily from haemoglobin. This change shifts the oxygen-haemoglobin dissociation curve to the right and is referred to as the Bohr effect. The explanation for the Bohr effect is that hydrogen ions (H+) bind to certain amino acids in haemoglobin, slightly alter its structure, and thereby decrease its oxygen carrying capacity. Thus lowered pH drives O2 off haemoglobin, making more O2 available for tissue cells. By contrast, elevated pH increases the affinity of haemoglobin for O2 and shifts the curve to the left.

· Partial pressure of carbon dioxide. CO2 also can bind to haemoglobin and the effect is similar to that of H+ (shifting the curve to the right). As PaCO2 rises, haemoglobin release O2 more readily. PaCO2 and pH are related factors because low blood pH (acidity) results from high PaCO2.As CO2 enters the blood, much of it is temporarily converted to carbonic acid (H2CO3). An enzyme in red blood cells called carbonic anhydrase catalyses this conversion. The carbonic acid thus formed in the red blood cells dissociates into hydrogen ions and bicarbonate ions (HCO3). As the H+ concentration increases pH decreases. Thus an increased PaCO2 produces a more acidic environment, which helps release O2 from haemoglobin. During exercise, lactic acid, a by-product of anaerobic metabolism within muscles also decreases the blood pH. Decreased PaCO2 (and elevated pH) shifts the saturation curve to the left.

· Temperature

As temperature increases so does the amount of O2 released from haemoglobin. Heat is a by-product of the metabolic reactions of all cells. Contracting muscle fibres release large amount of heat, which tends to raise the body temperature. Metabolically active cells require more O2 and liberate more acids and heat. The acids and heat, in turn, promote release of O2 from oxyhaemoglobin. During hypothermia cellular metabolism slows, reducing the need for O2 and increasing the O2 affinity for haemoglobin (a shift to the left on the saturation curve.)

· BPG 2,3- bisphospoglycerate (BPG) is a substance found in red blood cells that decreases the affinity of haemoglobin for O2 and thus helps to release O2 from haemoglobin. BPG is formed in red blood cells during glycolysis. The greater the level of BPG, the more O2 is released from haemoglobin. Certain hormones, such as thyroxin, human growth hormone, epinephrine, norepinephrine, and testosterone, increase the formation of BPG. People in higher altitudes have higher level of BPG.

Hypoxia is a deficiency of oxygen at the tissue level and is classified as different types according to the cause. These are

Hypoxic hypoxia a low PaO2 in the arterial blood resulting from high altitude, obstructions in the airways or fluid in the lungs.

Anaemic hypoxia too little functioning haemoglobin in the blood resultant from haemorrhage, anaemia, or failure of the haemoglobin to carry its normal complement of O2 (carbon monoxide poisoning).

Stagnant (ischaemic) hypoxia blood flow to the tissues is so low that adequate O2 is not delivered even though PaO2 and oxyhaemoglobin are normal.

Histotoxic hypoxia blood delivers adequate O2 to tissues, but the tissues are unable to use it properly because of the action of a toxic agent (cyanide poisoning).