Physiology for practice: delivering oxygen to the cells
VOL: 98, ISSUE: 40, PAGE NO: 62
Marion Richardson, BD, RGN, DipNurs, CertEd, RNT, is senior lecturer, University of Hertfordshire, HatfieldThere are approximately 50 million million cells in the human body, and every single one needs oxygen in order to function and survive.
All living matter exerts a pressure which is the result of the atoms within it colliding with one another. The atmosphere exerts a pressure that can be measured and is known to be 760mmHg (millimetres of mercury) at sea level. Pressure can also be measured in kilos Pascal (kPa) - atmosphere is 101.3 kPa - or in centimetres of water (as when measuring central venous pressure). For the purposes of this physiological discussion, measurements will be in kPa, but the figures may be converted using the formula 1kPa = 7.5mmHg = 10.2 cm H2O. The atmosphere is made up of a mixture of gases, of which the most important physiologically is oxygen (O2). Inspired air consists of approximately 21% oxygen, 79% nitrogen (N2) and small amounts of other gases, including water vapour and carbon dioxide (CO2). Within the atmosphere, each gas exerts its own pressure, known as the partial pressure, and the total pressure of the mixture is equal to the sum of the pressures of all the gases within it. Since we know that atmospheric pressure is 101.3 kPa and that oxygen accounts for 21% of the mixture, we can calculate that the partial pressure of oxygen, usually written as PO2, in atmospheric air at sea level is 21.2 kPa. The P N2 can be similarly calculated as 79.6 kPa, PCO2 as 0.04 kPa and water (H2O) as 0.5kPa. Air in the lungs
As atmospheric air passes through the respiratory tract it becomes humidified with more water vapour. This means that the partial pressure of water within the mixture increases and, as a result, the partial pressures of the other gases in the mixture are reduced because the total pressure remains the same. The partial pressures are further modified as the gases combine with the air in the physiological 'dead space' in the respiratory tract before finally meeting and mixing with the gas mixture in the alveoli. Partial pressures of the various gases in atmospheric air and alveolar air are compared in Table 1. It will be noted that the alveolar PO2 is considerably less than atmospheric PO2, and alveolar PCO2 and water pressure are higher, although the total pressure remains constant. How oxygen moves into and out of the blood
The partial pressures of gases in the alveoli and in the vast capillary network surrounding them are different. Cells throughout the body remove oxygen from the blood to use and they give to the blood the waste products of their metabolism which are converted into and carried as carbon dioxide. This 'deoxygenated' blood travels via the veins and heart to the lungs, where gaseous exchange takes place and the gases move from areas of high pressure to areas of low pressure by simple diffusion across the alveolar/capillary membrane. Gaseous exchange is possible because of this difference of pressures (the pressure gradient) and because the membrane between the alveoli and capillaries is very thin. The system is made more efficient because the vast network of alveoli and surrounding capillaries means that there is usually a plentiful supply of blood and air available. Within the lungs, transfer of oxygen into the blood (and carbon dioxide out) is rapid and efficient. Blood is in close proximity to alveolar air for approximately 0.8 seconds, but it takes only about 0.2 seconds for gaseous exchange to take place. This provides a very generous margin if physiology deviates from normal - for example, during exercise or in respiratory disease. Blood arriving at the lungs has a PO2 of 5.3 kPa and a PCO2 of 6.1 kPa (Fig 1). When alveolar air and this blood are in close proximity at the alveolar membrane, gases rapidly diffuse across the membrane until their pressures are equal on either side. Blood leaving the lungs for the heart contains oxygen and carbon dioxide at virtually the same partial pressures as those contained within the alveoli, so that the normal pulmonary vein and systemic arterial partial pressure of oxygen (PaO2) is 13.3 kPa and PaCO2 is 5.3 kPa (Fig 2). Gaseous exchange cannot take place in the majority of the circulatory system because the vessel walls are too thick, but it can and does occur across the capillaries which supply the cells of the structures and organs of the body. At the tissues, gases diffuse, again across pressure gradients and thin membranes. Oxygen is given up to the tissues and the blood receives carbon dioxide produced by the tissues. Partial pressures of oxygen and carbon dioxide within venous blood arriving at the lungs are the same as those within the cells (Fig 2), since the gases cannot cross the thicker membranes of blood vessels in the rest of the circulation. Oxygen transport in the blood
At rest, the cells of the body use up 250ml of oxygen every minute and more during activity, illness or disease. The blood must deliver this constant supply or cells will quickly begin to fail and die. Oxygen is carried in the blood in two ways - 1% is transported simply dissolved in the blood - that is, in solution. Oxygen does not dissolve particularly well in blood, and if all the oxygen needed by the body were to be carried by this method, a blood volume in excess of 80 litres would be required to supply the cells' needs. Although only a small amount of oxygen is carried in this way, it is an important 1% for the following reasons: - It maintains the pressure gradients necessary for diffusion of gases; - It is the only oxygen that is 'free' to be measured and is the fraction that is measured when estimating arterial blood gases; - It governs the amount of oxygen that can be carried bound to haemoglobin (Hb). Haemoglobin
Normally, 99% of oxygen is carried bound to haemoglobin and, once bound, is no longer free to exert a pressure or to be measured in blood gas analysis. Haemoglobin is a conjugated protein found in red blood cells and consists of four haem groups, containing iron and four polypeptide chains. Each of these haem groups can combine with one molecule of oxygen to form oxyhaemoglobin, which is bright red and gives arterial blood its distinctive colour. This process is known as oxygenation. Every molecule of haemoglobin can thus carry four molecules of oxygen. Normal haemoglobin concentration is 2.2mmol/L (or 15g/dl) blood, and each molecule of haemoglobin can combine with four molecules of O2, so the oxygen capacity is 8.8mmol/L (1mmol O2 = 22.4ml). Amounts of oxygen carried bound to haemoglobin can thus be far in excess of the normal requirements of the body. A simple calculation allows us to see that the body, which needs 250ml of O2 each minute at rest, actually has theoretically available almost four times as much as needed - 8.8 x 22.4 (= 197.12ml per litre) x 5 litres pumped out of the heart each minute = 986ml per minute. In normal physiological circumstances, however, not quite all the available haemoglobin-binding sites become bound with oxygen, but about 97-98% do - this is the 'oxygen saturation' (SpO2) that is recorded by pulse oximetry. There are many reasons why pulse oximetry may give misleading information, but an important physiological reason is that, while haemoglobin may be fully bound with O2, haemoglobin levels may be very low (for example, in severe anaemia or in hypovolaemia). Pulse oximetry readings will be within normal limits but the blood is unable to carry sufficient oxygen to supply the needs of the cells throughout the body. Arterial blood gas analysis is not affected by fluctuating Hb levels and so will always give an accurate recording of arterial gas pressures. There is always 1% of oxygen in solution and 99% bound to haemoglobin and, as the O2 in solution is used, some of the bound O2 will be released so that this ratio (1:99) is maintained. Explaining the oxygen-haemoglobin dissociation curve
Oxygen does not bind to each haem molecule with the same ease, and a graph plotting haemoglobin saturation against PO2 is not linear (Fig 3). The first haem group combines with O2 with relative difficulty, the second and third groups combine more easily and the fourth with the greatest difficulty of all. It can be seen from Fig 3 that at a PO2 of 5.3 kPa, as in blood arriving at the lungs, almost 70% of the haemoglobin sites are bound with oxygen, and exposure to a PO2 of 13.3 kPa at the alveoli will allow up to 98% of the haemoglobin to become saturated with O2. At the tissues, O2 is unloaded from the haem molecules in response to the fall in PO2, so that a tissue PO2 of 5.3 kPa will mean that oxygen from the 97-70% range can be removed for use. The venous blood returning to the heart contains less oxygen but is not completely deoxygenated. The 's' shape of the oxygen-haemoglobin dissociation curve is important physiologically for a number of reasons. Normal physiological function occurs over only a small part of this curve, and a large reserve is available in the event of a fall in arterial partial pressure of oxygen, such as during exercise, at altitude or in lung disease. Even when PaO2 is only 8 kPa, 90% saturation of haemoglobin with oxygen will be achieved in blood leaving the lungs (point x in Fig 3). During strenuous exercise it is possible to achieve a PaO2 at the tissues of as little as 2 kPa, and this will allow 80% of the bound oxygen to be released (point y in Fig 3). The greater the demand for oxygen at the tissues, the more is released from haemoglobin. Conclusion
The body works very efficiently to extract oxygen from the air we breathe and to deliver it in sufficient amounts to meet the constant and changing demands of the tissues. Arterial blood gas and pulse oximetry estimations allow us to assess and monitor this efficiency so that therapy can be instigated if necessary.