Hypoxia refers specifically to the situation in which tissues are unable to undergo aerobic metabolism. Hypoxaemia refers specifically to reduced PaO2. This can result from either a failure of O2 delivery or a failure of O2 utilisation. The following conditions must be fulfilled for cells to utilise O2 for aerobic metabolism.
Hypoxia refers specifically to the situation in which tissues are unable to undergo aerobic metabolism. Hypoxaemia refers specifically to reduced PaO2. This can result from either a failure of O2 delivery or a failure of O2 utilisation. The following conditions must be fulfilled for cells to utilise O2 for aerobic metabolism:
Adequate arterial O2 tension (PaO2) – blood leaving the lungs must be adequately oxygenated.
Adequate O2-carrying capacity – blood must have an adequate haemoglobin (Hb) concentration.
Adequate cardiac output (CO) and arterial flow ensures that the O2 carried by Hb reaches the tissues.
Adequate mitochondrial function – the cells must be able to use O2 effectively for aerobic metabolism.
Hypoxia is therefore classified in terms of failure of one or more of the processes above:
Hypoxaemic hypoxia – caused by low PaO2. When PaO2 falls below 8 kPa, there is a steep fall in the saturation of Hb (see Chapter 8, Figure 8.2), which reduces O2-carrying capacity.
Anaemic hypoxia – PaO2 is normal but O2-carrying capacity is reduced. This is exemplified by severe anaemia and carbon monoxide poisoning (see Chapter 8).
Stagnant hypoxia – PaO2 and Hb concentration are normal, but circulatory failure means that tissue O2 delivery is reduced. This is exemplified by cardiogenic shock and acute limb ischaemia following an arterial embolus.
What are the causes of hypoxaemic hypoxia?
Hypoxaemia can be classified according to aetiology:
Hypoxaemia resulting from hypoventilation is described in detail in Chapter 18. In brief:
Alveolar diffusion is discussed in detail in Chapter 10, but in summary:
Diffusion limitation is rarely a cause of hypoxaemia.
PAO2 and pulmonary capillary O2 tension have normally reached equilibrium before the red blood cell has travelled a third of the way along the pulmonary capillary.
Diffusion limitation can cause hypoxaemia when:
– The alveolar–capillary barrier is thickened, as occurs in pulmonary fibrosis or severe pulmonary oedema.
– Inspired O2 tension is low, as occurs at high altitude (altitude may also cause pulmonary oedema – see Chapter 87).
Shunting is said to occur when blood passes from the right side to the left side of the heart without taking part in gas exchange. Deoxygenated venous blood consequently passes directly into the arterial system and mixes with arterial blood, decreasing PaO2.
A shunt can either be physiological or pathological:
Physiological shunt, subclassified as either anatomical or functional:
– Anatomical shunt. Deoxygenated blood enters the left side of the heart for anatomical reasons, such as:
▪ Bronchial circulation. Most of the venous blood from the large airways drains directly into the pulmonary veins, returning to the left side of the heart.
▪ Thebesian veins. A small amount of coronary venous blood drains directly into the four chambers of the heart via the Thebesian veins. The blood that drains into the left atrium and the left ventricle (LV) contributes to the anatomical shunt.
– Functional shunt. A proportion of the pulmonary blood passes through poorly ventilated alveoli in the lung base. Blood leaving these alveolar capillaries will therefore not be fully oxygenated (i.e. there is a local V̇/Q̇ mismatch; see Chapter 15).
Pathological shunt, classified on the basis of its location:
– Intra-cardiac; for example, as the result of a ventricular septal defect (VSD). Normally, the pressure in the LV is higher than that in the right ventricle. Accordingly, blood flows through a VSD in a left-to-right direction. However, if there were an increase in right ventricular pressure (such as in Eisenmenger’s syndrome or when there is right ventricular outflow tract obstruction such as in tetralogy of Fallot), blood flow may change to a right-to-left direction, resulting in a pathological shunt.
– Through large communicating vessels, exemplified by a direct communication between the pulmonary artery and either the pulmonary vein (pulmonary arteriovenous malformation, AVM) or the aorta (patent ductus arteriosus, PDA). Shunts may also be iatrogenically created, such as in the Blalock–Taussig shunt used to palliate tetralogy of Fallot. In common with a VSD, the direction of blood flow depends on the pressure in each vessel:
▪ A pulmonary AVM has right-to-left blood flow and therefore results in a pathological shunt because pulmonary arterial pressure is greater than pulmonary venous pressure. Pulmonary AVMs are classified as congenital or acquired. The latter is exemplified by the multiple pulmonary AVMs that occur in hepatic cirrhosis, resulting in hepatopulmonary syndrome.
▪ A PDA usually has left-to-right blood flow because aortic pressure is normally higher than pulmonary arterial pressure. However, the direction of blood flow may change if pulmonary arterial hypertension develops, as can occur with hypoxic pulmonary vasoconstriction in a neonate, resulting in pathological shunt.
– Intra-pulmonary shunts. These constitute by far the commonest cause of pathological shunts. Shunting occurs when alveoli are perfused but are unable to participate in gas exchange. This may occur when alveoli are completely filled with fluid (e.g. as occurs in pulmonary oedema or pneumonia) or as a result of a proximal airway occlusion (e.g. with bronchial obstruction or one-lung ventilation).