Transport of Oxygen

Oxygen is vital for life-sustaining aerobic respiration. Gener­ally, there are two types of oxygen transfer in the body: convection and diffusion. Convection refers to the active process where oxygen is moved in circulation through mass transport.

7.7.1 Convective Transport of Oxygen

7.7.1.1 Oxygen Uptake into the Bloodstream

Oxygenation of deoxygenated venous blood takes place in the pulmonary capillaries, as oxygen diffusion takes place through the alveolar-capillary membrane depending on the concentration gradient.

7.7.1.2 Haemoglobin and Its Role in Oxygen Transport

Oxygen is transported in the blood in two forms: firstly bound to haemoglobin (Hb) and secondly as a gas dissolved in plasma.

After diffusion through the alveolar membrane, oxygen binds to haemoglobin to form oxyhaemoglobin in the pulmo­nary capillaries. One molecule of haemoglobin can carry up to four molecules of oxygen and can be released in a revers­ible manner when needed. The binding of an oxygen mole­cule to haeme changes the shape of the globin chain, thereby changing the quaternary structure of haemoglobin. It makes it easier for subsequent oxygen molecules to bind to haemoglobin molecules with greater affinity, a phenomenon called cooperativity. This phenomenon can be described using a sigmoid-shaped oxyhaemoglobin dissociation curve (ODC). The curve has some characteristic features with spe­cific physiological significance.

Major events during oxygen dissociation are the follow­ing: (1) The curve is S-shaped with a plateau showing nearly 98.3% saturation. (2) At a pO₂ of 70 mmHg, Hb is fully saturated even though the alveolar pO₂ is 100 mmHg. It is advantageous in situations where Hb can bind to enough oxygen even though the oxygen level can fall to low levels, such as at high altitudes and in some disease conditions.

Haemoglobin exists in two forms: The two forms are termed taut (T) and relaxed (R). Taut (T) has a low affinity for oxygen, and relaxed (R) has a high affinity for oxygen. In the tissues, where the environment is rich in carbon dioxide and low in pH, the taut form of haemoglobin commonly occurs, favouring oxygen delivery to the tissues being dissociated from the haemoglobin. In the reverse conditions, especially in the alveoli where the carbon dioxide is low and the pH is higher with the high partial pressure of oxygen, the relaxed form of haemoglobin is found to be bound strongly with oxygen. This phenomenon is known as the Bohr effect.

The oxygen capacity of haemoglobin is expressed by the maximum volume of oxygen that 1 g of haemoglobin can combine with, also known as Hufner's constant. The theoret­ical maximum oxygen carrying capacity of haemoglobin is 1.39 mL O₂∕g Hb. In fact, the oxygen capacity of haemoglobin is lower than the calculated value, and according to Nunn's Applied Respiratory Physiology, 1.306 (or 1.31) mL/g is the accepted value for clinical purpose. This is partly due to altered forms of haemoglobin, such as methaemoglobin and carboxyhaemoglobin, which reduce the capacity of haemoglobin to carry oxygen.

Haemoglobin oxygen saturation is the percentage of the number of occupied oxygen-binding sites out of the maxi­mum number of available oxygen-binding sites. P50 is the partial pressure of oxygen at which haemoglobin is 50% saturated.

7.7.1.2.1 Role of 2,3-DPG

An organic phosphate, 2,3-diphosphoglycerate (2,3-DPG) is produced during glycolysis and found in red blood cells that supports the release of oxygen from haemoglobin. High concentrations of oxyhaemoglobin in the erythrocytes sup­press the production of 2,3-DPG by inhibiting the enzyme that forms 2,3-DPG. However, when oxyhaemoglobin levels are low, 2,3-DPG synthesis increases. It occurs with chronic hypoxia due to high altitudes and anaemia, and 2,3-DPG decreases the affinity of haemoglobin for oxygen. Under the anaemic condition, elevated production of 2,3-DPG occurs, which shifts the ODC to the right, thereby increasing oxygen delivery to the tissues and minimising the hypoxic effects. On the contrary, in banked donor blood, 2,3-DPG is lost by

# indicting the decrease, " indicating the increase

metabolism as a result of reduced transfusion capacity of oxygen delivery to the tissues.

Blood oxygen content is the amount of oxygen carried in every 100 mL of blood.

This can be estimated by the sum total of O₂ transported as bound Hb and the O2 dissolved in solution form = (1.34 ? Hb ? SpO₂ ? 0.01) + (0.023 ? P_aO₂):

[SO₂ = saturation of Hb with oxygen in percentage; Hb = gram haemoglobin concentration (Hb in grams/ 100 mL blood). pO₂ = partial pressure of oxygen (0.0225 mL of O₂ dissolved per 100 mL plasma per kPa, or 0.003 mL per mmHg)].

When applied for a healthy adult male, the oxygen content of arterial blood is as given:

The arterial oxygen saturation (SpO₂) = 98.3%, Hb = 15 g/100 mL, and arterial partial pressure of oxygen (P_aO₂) = 13.3 kPa.

The oxygen content of arterial blood (CaO₂) is CaO₂ = 19.758 + 0.3 = 20.058 mL/100 mL.

Similarly, the oxygen content of mixed venous blood can be calculated.

The normal values of mixed venous oxygen saturation (SvO₂) = 75% and partial venous pressure of oxygen (PvO₂) = 6 kPa, so CvO₂ = 15.2 + 0.1 = 15.2 mL/100 mL.

7.7.1.3 Foetal and Neonatal Oxygen Transport

The respiratory system plays a vital role in transporting oxygen to the tissues that, in turn, is utilised in aerobic metabolism for the supply of energy during the foetal and neonatal stages. The oxygen delivery to the foetal tissues depends mainly on the oxygen consumption by the tissues, the pressure gradient and the affinity between haemoglobin and oxygen. Oxygen is transported by blood either in the dissolved state or bound to haemoglobin. Foetal haemoglobin plays an essential role in transporting and delivering oxygen during the foetal and neonatal stages. In humans, the foetal haemoglobin, denoted by HbF, comprises two alpha and gamma chains (α2γ2). Oxygen has greater affinity for this haemoglobin than adult haemoglobin (HbA), favouring oxy­gen binding with haemoglobin across the placenta.

7.7.1.4 Non-classical Role of RBC in Oxygen Delivery to Tissues

During circulation, the red blood cells can sense the oxygen status of tissues through their degree of deoxygenation and use this sense to stimulate the release of vasodilatory compounds such as nitric oxide (NO) or ATP, which stimu­late blood flow to hypoxic tissues. There are three mechanisms by which this happens: (a) release ATP that stimulates endothelial cells for the release of NO; (b) upon deoxygenation, it triggers S-nitroso-Hb^- to release nitric oxide; and (c) deoxyhaemoglobin reduces nitrite (NO₂^-) to vasoactive NO by means of nitrite reductase activity.

7.8