O2 is carried within the circulation from the lungs to the tissues in two forms.
O2 is carried within the circulation from the lungs to the tissues in two forms:
Bound to haemoglobin (Hb), accounting for 98% of O2 carried by the blood. Each gram of fully saturated Hb can bind 1.34 mL of O2 (this is called Hüfner’s constant).
Dissolved in plasma, accounting for 2% of O2 carried by the blood. The volume of O2 dissolved in blood is proportional to the partial pressure of O2 (this is Henry’s law).
The total volume of O2 carried by the blood is the sum of the two:
O2 content per 100 mL of blood = (1.34 × [Hb] × SaO2/100%) + 0.023 × PO2, where 1.34 mL/g is Hüfner’s constant at 37°C for typical adult blood, [Hb] is the Hb concentration (g/dL), SaO2 is the percentage Hb O2 saturation, 0.023 is the solubility coefficient for O2 in water (mLO2.dL–1.kPa–1) and PO2 is the blood O2 tension (kPa).
For typical arterial blood ([Hb] = 15 g/dL, SaO2 = 97% and PO2 = 13.0 kPa):
O2 content per 100 mL arterial blood (CaO2) = (1.34 × 15 × 0.97) + 0.023 × 13 = 19.50 + 0.30 = 19.8 mL
whereas venous blood (Hb O2 saturation of 75%, PO2 = 5.3 kPa) contains
O2 content per 100 mL venous blood (CvO2) = (1.34 × 15 × 0.75) + 0.023 × 5.3 = 15.08 + 0.12 = 15.2 mL
The above worked example demonstrates that Hb is a much more efficient means of O2 carriage than O2 dissolved in plasma. However, it would be wrong to think that dissolved O2 is unimportant. The O2 tension of blood is determined from the amount of O2 dissolved in plasma – the PO2 within a red blood cell (RBC) is low because all the O2 is bound to Hb. Fick’s law of diffusion states that diffusion occurs along a pressure gradient, so O2 diffuses to the tissues from the dissolved portion in the plasma, not from Hb itself. O2 then dissociates from Hb as plasma PO2 falls, replenishing the O2 dissolved in the plasma.
Very little O2 is stored in the body, which means that periods of apnoea can rapidly lead to hypoxia. In addition to O2 in the lungs (within the functional residual capacity), O2 is stored in the blood (dissolved in plasma and bound to Hb) and in the muscles (bound to myoglobin).
As described above, approximately 20 mL of O2 is carried in each 100 mL of arterial blood and 15 mL of O2 per 100 mL of venous blood. At sea level, a 70‑kg man has approximately:
5 L of blood, containing approximately 850 mL of O2;
A further 250 mL of O2 bound to myoglobin;
450 mL of O2 in the lungs when breathing air.
This gives a total of 1550 mL of O2.
An adult’s resting O2 consumption is approximately 250 mL/min, which means that apnoea need only occur for a few minutes before the onset of significant cellular hypoxia. Hypoxic damage occurs even more quickly when there is reduced O2-carrying capacity (e.g. anaemia or carbon monoxide poisoning) or an increased rate of O2 consumption (e.g. in children).
Low-flow and minimal-flow anaesthesia are anaesthetic re-breathing techniques used to reduce the cost and environmental impact of general anaesthesia. Fresh gas flow rates are set below alveolar ventilation, and the exhaled gases are reused once CO2 has been removed. Either low (<1000 mL/min) or minimal (<500 mL/min) fresh gas flow rates are used. The other requirements for this technique are a closed (or semi-closed) anaesthetic circuit (usually a circle system), a CO2 absorber, an out-of-circle vaporiser and a gas analyser.
When using low fresh gas flows, the anaesthetist must ensure that the gases absorbed by the patient (i.e. O2 and volatile anaesthetic agents) are replaced. The resting adult O2 consumption is 250 mL/min; therefore, the minimum required O2 delivery rate is 250 mL/min. However, most anaesthetists would deliver a slightly greater rate of O2 than this (300–500 mL/min) to ensure that the patient never becomes hypoxaemic.
RBCs are small, flexible, biconcave discs (diameter 6–8 µm) that are able to deform to squeeze through the smallest of capillaries (around 3 µm in diameter). The cell membrane exterior has a number of antigens that are important in blood transfusion medicine: the ABO blood group system is composed of cell surface carbohydrate-based antigens, while the rhesus blood group system is formed by transmembrane proteins (see Chapter 73).
RBCs are unique as they have no nucleus and their cytoplasm has no mitochondria – effectively, RBCs can be considered to be ‘bags of Hb’. By the time blast cells have become reticulocytes – the final cell stage of erythropoiesis – their nuclear DNA has been lost. Reticulocytes instead have a network of ribosomal RNA (hence the name: reticular, meaning net-like). Reticulocytes normally make up 1% of circulating RBCs, but this proportion may be increased if erythropoiesis in the bone marrow is highly active, such as in haemolytic anaemia or following haemorrhage.
As the RBC cytoplasm does not contain mitochondria, aerobic metabolism is not possible. RBCs are unique, as they constitute the only cell type that is entirely dependent on glucose and the glycolytic pathway (see Chapter 77) to provide energy for metabolic processes – even the brain can adapt to use ketone bodies in times of starvation.
What is Hb?
Hb is a large iron-containing protein contained within RBCs. The most common form of adult Hb is HbA, accounting for over 95% of the circulating Hb in the adult. It has a quaternary structure comprising four polypeptide globin subunits (two α-chains and two β-chains) in an approximately tetrahedral arrangement. The four globin chains are held together with weak electrostatic forces. Each globin chain has its own haem group, an iron-containing porphyrin ring with iron in the ferrous state (Fe2+). O2 molecules are reversibly bound to each haem group through a weak coordinate bond to the Fe2+ ion. In total, four O2 molecules can be bound to each Hb molecule, one for each haem group (Figure 8.1).
What is cooperative binding?
Hb is essentially either fully saturated with O2 (oxyhaemoglobin) or fully desaturated (deoxyhaemoglobin) due to cooperativity.
Cooperative binding is the increase in O2 affinity of Hb with each successive O2 binding:
The first O2 molecule binds with relative difficulty – strong electrostatic charges must be overcome to achieve the required conformational changes in the Hb molecule. This conformation is referred to as the ‘tense’ conformation, where the β-chains are far apart.
Once the first O2 molecule has bound, the conformation of Hb changes and the β-chains come closer together.1 This new conformation results in a second O2 molecule having a higher binding affinity, thus requiring less energy to bind.
Once the second O2 molecule has bound, the third is easier to bind, and so on. In fact, the fourth O2 molecule binds 300 times more easily than the first.
What is the oxyhaemoglobin dissociation curve?
The oxyhaemoglobin dissociation curve describes the relationship between SaO2 and blood O2 tension (Figure 8.2). As discussed above, the cooperative binding of Hb is responsible for the curve’s sigmoid shape, which has important clinical consequences:
The upper portion of the curve is flat. At this point, even if PaO2 falls a little, SaO2 hardly changes. However, when a patient’s PaO2 is pathologically low (e.g. in patients with respiratory disease), the patient is at a much steeper part of the curve; here, a small decrease in PaO2 results in a large desaturation.
The steep part of the curve is very important in the peripheral tissues, where PO2 is low: a large quantity of O2 is offloaded for only a small decrease in PO2.