Oxygen Transport

From an atmospheric level of 21kPa (21%), the partial pressure of oxygen falls in 3 stages before the arterial blood is reached. Firstly the inspired air is humidified by the upper respiratory tract, the saturated vapour pressure of water (6.2kPa or 47mmHg) reducing the PO2 to around 19.7kPa (148mmHg) - ( The Physiology of Oxygen Delivery, Update in Anaesthesia 1999;10:3). In the alveoli the continuous exchange of carbon dioxide for oxygen reduces the PO2 to about 14.4kPa (108mmHg) and finally the small physiological shunt normally present reduces it to approximately 13.3kPa (100mmHg).

Oxygen carriage

After transfer of oxygen across the alveolar capillary membrane, an efficient carriage system is needed to transport it to the tissues for use in cellular respiration. The oxygen content in the blood is the sum of that bound to haemoglobin (Hb) and that dissolved in plasma, which is normally a minor contribution in patients breathing air. Hb is a large protein containing 4 subunits, each containing a ferrous (Fe2+) ion within a haem group. Up to 4 oxygen molecules can bind reversibly to each Hb molecule, one to each of the Fe2+ sites. The main factor that determines the extent of oxygen binding to Hb is the PO2, the relationship between which is shown in figure 8. The initial flat part of the curve occurs because the binding of the first oxygen molecule causes a small structural change to Hb facilitating the binding of subsequent oxygen molecules. The shape of the curve means that a fall in PO2 from the normal arterial value will have little effect on the Hb saturation (and therefore oxygen content) until the steep part of the curve is reached, normally around 8kPa (60mmHg). Once the PO2 has reached this level, however, a further decrease in PO2 will result in a dramatic fall in the Hb saturation.

Several factors can change the affinity of Hb for oxygen, resulting in the curve moving to the right (acidosis, temperature or 2,3-DPG (2,3 diphosphoglycerate) or to the left (foetal Hb, alkalosis, temperature or 2,3-DPG ). An index of the position of the Hb-O2 dissociation curve is given by the P50, the PO2 at which Hb is 50% saturated.

Movement of the curve to the right decreases the affinity of Hb for oxygen. This is physiologically useful in the tissues, where the slightly acidic environment serves to improve oxygen unloading from the blood - the Bohr Effect. A left shift of the curve increases the affinity of Hb for oxygen, producing a higher saturation at a given PO2. This acts to improve oxygen loading in the pulmonary capillary (slightly alkaline) and is greatly advantageous in the foetus, where the PO2 is low (see later).

1g of Hb can carry 1.34ml of oxygen if fully saturated. At a PO2 of 13.3kPa (100mmHg), Hb is normally about 97% saturated with oxygen. If the Hb concentration is 150gm/litre (15gm/100ml), arterial blood will therefore hold approximately 200ml/litre. With a cardiac output of 5 litre/min, the amount of oxygen available in the circulation is 1,000ml/min. Of this, approximately 250ml/min is used at rest, the Hb in venous blood being about 75% saturated.

The amount of oxygen dissolved in plasma is 0.23ml/litre/kPa (0.03ml/litre/mmHg). Whilst this is only about 3ml/litre when breathing air, it can be raised substantially by the use of hyperbaric pressure, reaching a level adequate to supply tissue requirements by breathing 100% oxygen at 3 atmospheres pressure. This can be used to sustain oxygenation if the patient's Hb is either insufficient or ineffective.

Special circumstances

It is useful to study the various specific physiological responses and adaptations which occur in response to changes in circumstances, in order to understand more clearly the different physiological mechanisms already described and the effects of anaesthesia and disease. These include:

Exercise

During exercise oxygen consumption can rise from 250 to over 3,000ml/min. Changes in response to this increased oxygen demand include:

• cardiac output
• ventilation
• extraction of oxygen from the blood

Above a certain level, oxygen delivery cannot meet tissue demands, and anaerobic metabolism occurs, leading to lactic acid production.

Altitude

The acute response to the low arterial PO2 resulting from high altitude is driven by the action of peripheral chemoreceptors to produce hyperventilation (as well as an increase in cardiac output). The resulting fall in the alveolar PCO2 leads to an increase in the alveolar PO2 (by the alveolar gas equation) which increases the arterial PO2. The associated decrease in arterial PCO2, however, reduces the drive at the central chemoreceptors, limiting the hyperventilation response. Metabolic compensation occurring over the next 2-3 days, involving an increase in renal HCO3^- excretion and a subsequent fall in plasma and CSF HCO3^-, reduce this unwanted effect.

Later responses that improve oxygen carriage include:

• 2,3 DPG , leading to a right shift of the dissociation curve
• polycythaemia

Foetus

Oxygenation of foetal blood comes from the maternal circulation via the placenta. Blood leaving the placenta in the umbilical vein has a PO2 of only around 4.0kPa (30mmHg) and yet has an oxygen content of approximately 130ml/litre. The mechanisms by which this is achieved are:

• a left shift of the foetal Hb-O2 dissociation curve, with a P50 of 2.5kPa (19mmHg) [compared with a P50 for adult Hb of 4.0kPa (30mmHg)]
• a raised Hb concentration (180gm/litre - 18gm/ 100ml - at term)

The increased Hb concentration increases the oxygen carrying capacity, whilst the left shift of the Hb-O2 dissociation curve results in an increase in Hb affinity for oxygen (see earlier) and therefore a higher saturation at low PO2.

Causes of hypoxia

Hypoxia indicates the situation where tissues are unable to undergo normal oxidative processes because of a failure in the supply or utilisation of oxygen. The causes of hypoxia can be grouped in to 4 categories:

Hypoxic hypoxia

Hypoxic hypoxia is defined as an inadequate PO2 in arterial blood. This can result from an inadequate PO2 in the inspired air (such as at altitude), major hypoventilation (from central or peripheral causes) or from inadequate alveolar-capillary transfer (such as shunt or V/Q mismatch).

Anaemic hypoxia

The oxygen content of arterial blood is almost all bound to Hb. In the presence of severe anaemia, the oxygen content will therefore fall in proportion to the reduction in Hb concentration, even though the PO2 is normal. The normal compensatory mechanism to restore oxygen delivery is an increase in cardiac output, but when this can no longer be sustained tissue hypoxia results. Conditions in which Hb is rendered ineffective in binding oxygen, such as carbon monoxide poisoning, produce a reduction in oxygen carriage similar to anaemia.

Circulatory or stagnant hypoxia

If circulatory failure occurs, even though the oxygen content of arterial blood may be adequate, delivery to the tissues is not. Initially tissue oxygenation is maintained by increasing the degree of oxygen extraction from the blood, but as tissue perfusion worsens this becomes insufficient and tissue hypoxia develops.

Histotoxic hypoxia

This describes the situation where cellular metabolic processes are impaired to prevent oxygen utilisation by the cells, even though oxygen delivery to the tissues is normal. The best-known cause of histotoxic hypoxia is cyanide poisoning, which inhibits cytochrome oxidase. 

Non-Respiratory Lung Functions

Whilst the main function of the lung is for respiratory gas exchange, it has several other important physiological roles.

These include:

• reservoir of blood available for circulatory compensation
• filter for circulation:
  • thrombi, microaggregates etc
• metabolic activity:
  • activation:
    • angiotensin III
  • inactivation:
    • noradrenaline
    • bradykinin
    • 5 H-T
    • some prostaglandins
• immunological:
  • IgA secretion into bronchial mucus

In summary, the article has outlined the many complex processes by which gas exchange in the body is maintained and regulated. With a fuller understanding of how these processes can be disturbed, the anaesthetist is better placed to manage the resulting problems logically and effectively. Readers are recommended to read this article with  The Physiology of Oxygen Delivery, (Update in Anaesthesia 1999;10:3) and  Volatile Anaesthetic Agents, (Update in Anaesthesia 2000;11:15). 

This article contained links to the following additional information:

 Cardiovascular Physiology - Part 1

 The Physiology of Oxygen Delivery

 Volatile Anaesthetic Agents

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