The normal pulmonary circulation distributes deoxygenated blood at low pressure and high flow to the pulmonary capillaries for the purposes of gas exchange. The structure of pulmonary blood vessels varies with their function—from large elastic conductance arteries, to small muscular arteries, to thin-walled vessels involved in gas exchange.
Pulmonary vascular resistance (PVR) is about one-tenth of systemic vascular resistance, with the small muscular and partially muscular arteries of 50 to 150 µm diameter being the site of the greatest contribution to resistance. The gas-exchanging capillary surface area (c.125 m2) contains a blood volume of about 150 ml at any one time, with the blood–gas barrier being only 0.2 to 0.3 µm thick at its thinnest part. In the normal pulmonary circulation, a large increase in cardiac output causes only a small rise in mean pulmonary arterial pressure because PVR falls on exercise: this is accomplished by a combination of vascular distensibility and recruitment. Pulmonary blood flow is heterogeneous: gravity causes increased blood flow in the more dependent parts of the lung; within a horizontal region—or within an acinus—blood-flow heterogeneity is imposed by the branching pattern of the vessels.
Many neural and humoral mediators can influence pulmonary vascular tone, including nitric oxide and prostacyclin. Alveolar hypoxia causes constriction of the small pulmonary arteries, whereas systemic arteries dilate when hypoxic: this hypoxic pulmonary vascoconstriction can reduce venous admixture and improve arterial oxygenation in the presence of bronchial obstruction. Despite large regional differences in the matching of ventilation and perfusion within the normal lung, the overall lung ventilation–perfusion ratio is maintained remarkably steady at around 0.85.
The main function of the pulmonary circulation is respiratory gas exchange, a vital function that the lungs take over from the placenta at birth. The structure of the pulmonary circulation is highly adapted to fulfil this role. It receives the entire cardiac output from the right ventricle during each cardiac cycle, and this mixed venous blood is delivered at high flow but low pressure to the delicate alveolar structures where gas exchange occurs. Blood flow is matched closely to the regional ventilation within the lung to optimize and maintain systemic arterial oxygenation. This chapter discusses the anatomy and physiology of the pulmonary circulation.
Structure of the pulmonary circulation
The pulmonary arteries and bronchi, together with lymphatics, run in a single connective tissue sheath in the centre of pulmonary segments and lobules, the so-called bronchovascular bundle. The ‘conventional’ pulmonary arteries branch dichotomously and symmetrically, along with the airways, and they also give off extra branches between the conventional branching points, called ‘supernumerary’ or short branches. The intrapulmonary veins pursue a different course along the edges of lobules and segments, in the interlobular septa. The branching pattern of veins is similar to that of the pulmonary arteries.
The branching pattern of the pulmonary arteries can be described by a ‘divergent’ approach, where the main pulmonary artery is called generation 1, with each division giving rise to generation 2, 3, etc. An alternative is the ‘convergent’ approach where the most peripheral branch is numbered ‘order 1’, and the orders increase until the main pulmonary artery (order 17) is reached. Fig. 126.96.36.199 shows this arrangement going from the precapillary arteriole of order 1, whose diameter is about 13 μm, to the main pulmonary artery (order 17) with a diameter of 30 000 μm. Note the ninefold expansion in cross-sectional area of the pulmonary vascular bed from order 2 to order 1: it is these precapillary vessels that are often involved in disease processes that affect the pulmonary circulation. In the normal lung, the site of the greatest pulmonary vascular resistance (PVR) is in the small partially muscular and muscular pulmonary arteries (orders 4 to 6; 50–150 μm diameter).
The wall structure of the pulmonary arteries changes along their length depending on the function of the vessel (Fig. 188.8.131.52). All preacinar arteries have a complete muscular coat, but the muscle layer may be incomplete or absent in smaller intra-acinar vessels.
• Elastic arteries (orders 17–13)—these larger arteries have adventitial, muscular, and intimal layers. The media, or muscular layer, is bounded by internal and external elastic laminae, with three or more elastic laminae within the muscle coat. Medial thickness is about 1 to 2% of external diameter.
• Muscular arteries (orders 13–3)—these small arteries have a thicker muscle layer in relation to their external diameter (2–5%), and they possess only internal and external elastic laminae; in the smallest arteries, the internal elastic lamina disappears.
• Partially muscular arteries (orders 5–3)—the smooth muscle fibres investing the smallest pulmonary arteries taper off in a spiral, leading to an incomplete muscular coat (Fig. 184.108.40.206). Most arteries of 50 to 100 μm external diameter are partially muscular.
• Nonmuscular arteries (orders 5–1)—these arteries have no elastic laminae. The smooth muscle cell is replaced by pericytes whose basement membrane fuses with that of the endothelial cell lining the vascular lumen.
• Supernumerary arteries—these are small, relatively thin-walled arteries that branch sharply from the parent vessel between bifurcations of the conventional branching system, starting from orders 11 to 12. They provide a short cut for blood supplying the alveoli adjacent to the conduit arteries and bronchi, which would otherwise require a long and circuitous supply by the axial route.
• Pulmonary veins—the branching pattern and organization of the pulmonary veins is similar to that of the arteries, but with only 15 orders, because the 4 pulmonary veins converge on the left atrium without joining up to form an additional 2 orders. Veins do not have an internal elastic lamina. Their walls contain more elastic tissue and less muscle than arteries of the same size. There are supernumerary veins like the supernumerary arteries.
• Capillary network—the 300 million precapillary vessels lead into a network of alveolar septal capillaries with a blood volume (150 ml) equal to that in the pulmonary arterial or venous systems. The capillary surface area is about 125 m2 (c.86% of the alveolar surface area). Individual capillaries are not much wider than a single erythrocyte, hence the microvascular bed at normal vascular pressures is essentially a sheet of blood one red cell thick, exposed to alveolar gas on both sides. Alveolar capillaries have a thick side and a thin side. The thin side consists of the cytoplasmic extensions of the luminal endothelial cell and the alveolar epithelial cell with their fused basement membrane (0.2–0.3 μm across). The thick side, up to 2 μm across, contains collagen, elastin, and fibroblast processes to give structural support to the alveolus.
Pulmonary vascular resistance
The pulmonary circulation is a high-flow, low-pressure system whose vascular resistance is one-tenth of systemic vascular resistance. PVR is the ratio of the mean pulmonary arterial–venous pressure difference (Ppa − Ppv) to mean pulmonary blood flow (Qp):
The normal PVR is less than 2 mmHg/litre per min at rest.
PVR normally falls on exercise despite the increase in cardiac output, hence Ppa rises only modestly, perhaps from 15 mmHg at rest to 23 mmHg. The fall in PVR during exercise is accomplished by a combination of vascular ‘distensibility’ (vascular compliance) and ‘recruitment’ (number of parallel pathways with flow). Vascular recruitment means that a vessel goes from a state of zero flow to one of finite flow. An increase in pulmonary arterial pressure during exercise can distend pulmonary arteries. The total compliance of the pulmonary circulation is about 20 ml/mmHg, hence on heavy exercise, if all vascular pressures rose by 10 mmHg, pulmonary vascular volume would increase by 200 ml, provided vessels had not reached their limiting size.
The distribution of PVR can be partitioned into a three-segment model, which can be described as having (1) arterial, (2) ‘middle’, and (3) venous segments. In isolated lungs, about 20% of the total PVR lies in the distensible ‘middle’ segment (capillaries and small arteries and veins), with 40% each in the arterial and venous segments. This distribution can be altered by factors, e.g. hypoxia, that increase resistance predominantly in the ‘middle’ segment. Blood viscosity is a further factor that affects PVR, e.g. when polycythaemia increases PVR.
Distribution of pulmonary blood flow
Blood flow within the lung is heterogeneous in distribution. For example, between lung regions of secondary lobule size (c.10 cm3) there is a modest amount of gravity-dependent heterogeneity, with flow increasing with vertical distance (more to the lower zones than the upper zones). Within these lung regions and within the respiratory acinus there is a greater degree of heterogeneity, which is independent of gravity.
The effects of gravity are best illustrated by considering that, in the human erect posture at rest, mean pulmonary artery pressure (Ppa) at the level of the hilum is about 18 cmH2O, whereas the apex of the lung is 20 cmH2O above the hilum. Consequently, the apex of the lung will be perfused only during the systolic pressure peak. In the supine position, the apical blood flow increases, with the result that the distribution from apex to base becomes more uniform. During exercise, with the increase in cardiac output, both upper and lower zone blood flow increases, but the upper increases more than the lower, so that flow becomes more even. The role of gravity in determining pulmonary blood flow was extended by West and encompassed in the three-zone model of pulmonary circulation (Fig. 220.127.116.11). This model relies on the assumption that the site of major flow resistance is in the small vessels whose extravascular pressure is the alveolar pressure (Palv). There is no flow in zone I because Palv is greater than Ppa. Flow increases down zone II because the driving pressure increases by 1 cm of H2O for each 1 cm distance down the lung. Flow increases with distance down zone III, although ΔP (Ppa − Ppv) remains constant, because local PVR decreases due to capillary distension and recruitment. The driving pressure for blood flow is determined by the relationship between Palv, Ppa, and pulmonary venous pressure (Ppv) down the upright lung. A further zone (zone IV) is found at the lung base: in this zone, blood flow is observed to decrease with distance down the lung due to increased perivascular pressure in extra-alveolar vessels.
The branching pattern of pulmonary arteries imposes changes in perfusion that are independent of gravity. Within any given horizontal level of the upright lung, there is a decrease in blood flow in peripheral lung regions compared to central hilar regions. This is thought to be due to the reduction in Ppa in small acinar arteries with increasing distance from the hilum. This pattern is also seen at the level of the secondary lobule (the group of acini supplied by one terminal bronchiole), with a decreasing gradient of blood flow from the centre to the periphery.
Regulation of pulmonary vasomotor tone
The pulmonary circulation differs from the systemic in that it is under minimal resting tone and is almost fully dilated under normal conditions. Circulating and local production of vasodilators and vasoconstrictors contribute to the resting tone, with the balance tipped in favour of vasodilators. Nitric oxide, produced locally by endothelial cells, and the arachidonic acid metabolite prostacyclin, are important vasodilators that contribute to this low pulmonary vascular tone.
The autonomic nervous system interacts with humoral mediators and haemodynamic forces in the control of pulmonary vascular tone, autonomic innervation of the lung being via parasympathetic (cholinergic: predominantly vasodilator) and sympathetic (adrenergic: predominantly vasoconstrictor) nerves in the periarterial plexus.
Hypoxic pulmonary vasoconstriction
The pulmonary circulation responds to a reduction in the partial pressure of alveolar oxygen by vasoconstriction. This is opposite to the response to hypoxia in the systemic circulation, where tissue hypoxia leads to vasodilatation, hence improving tissue oxygen delivery. Hypoxic pulmonary vasoconstriction (HPV) probably plays little role in the normal distribution of pulmonary blood flow or regulation of ventilation–perfusion relationships in humans. However, in diseases characterized by airway obstruction, such as acute asthma or chronic obstructive lung disease, HPV can divert blood flow away from poorly ventilated lung regions, reducing venous admixture (shunt through poorly ventilated lung regions) and preserving arterial oxygenation. The magnitude of the response varies widely between individuals and is, at best, 50% efficient. It is noteworthy that populations indigenous to high-altitude regions, e.g. Tibetans, lack HPV with no obviously detrimental effect. At high altitude, with low atmospheric partial pressures of oxygen, HPV would lead to generalized vasoconstriction and pulmonary hypertension, which is presumably more detrimental than the lack of HPV.
In the normal lung, it is remarkable that pulmonary blood flow and ventilation are, in general, well matched given the heterogeneity of blood flow described above. Of course, regional ventilation is also under similar constraints and forces as the blood flow. In terms of the structure and function of the airways and alveoli, in brief, the airways run with the arteries in the bronchovascular bundle and the branching patterns are similar. Regional ventilation is under the influence of gravity: the lung sits in the thorax under its own weight, which leads to a gradient of intrapleural pressure, with more negative pressures at the top of the lung than at the bottom in the upright position. This means that the lung is more expanded at the apex than at the base at the end of a normal breath (functional residual capacity). Thus, the upper and lower parts of the lung are operating on different portions of their pressure–volume curves. The result is that, during normal breathing, greater ventilation is delivered to the bottom than to the top of the lung. This gradient of regional ventilation down the lung is reminiscent of the gradient of blood flow described above. In fact, with increasing distance up the lung, the rate of change of ventilation per unit of alveolar volume is somewhat less than the rate of change of perfusion (about one-third). This leads to large regional differences in the ventilation–perfusion ratio up the lung (Fig. 18.104.22.168): alveoli at the bottom of the lung are relatively overperfused, leading to a low ventilation–perfusion ratio (c.0.6); by contrast, alveoli at the apex of the lung are relatively under-perfused, leading to ventilation–perfusion ratios over 3.0. Nevertheless, the overall ventilation–perfusion ratio for the whole lung is approximately 0.85. The regional ventilation–perfusion ratio will determine the partial pressures of oxygen and CO2 found in the alveoli at a given level of the lung, and this will be reflected in the gas tensions found in pulmonary venous blood draining those alveoli. The result is that the Po2 is higher, and the Pco2 lower, in blood draining from the top of the lung, compared with the bottom. The matching of ventilation and perfusion in the normal lung ensures that the overall ventilation–perfusion ratio remains fairly constant with changes in posture or exercise.
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