Control of Pulmonary Blood Flow

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Control of Pulmonary Blood Flow; Pulmonary metabolism.


Reading assignment: Chapter 4 of West, Respiratory Physiology-the essentials, 7th ed.

Figure 1. Overview of the pulmonary circulation system


I.Key points about the pulmonary circulation system


  • The lungs are in series with the right and left heart. One important consequence of this arrangement is that blood flow through the lungs must equal the blood flow through the rest of the body. This makes the lungs an effective organ for gas exchange, filtering and metabolism. This arrangement also permits the pressures of the pulmonary and the systemic circulation systems to differ.
  • The pulmonary arteries carry de-oxygenated blood.
  • The pulmonary veins carry oxygenated blood.
  • The pulmonary arteries “travel” with the airways.
  • The pulmonary capillaries lie in the alveolar septa.
  • The pulmonary veins drain into the left atrium.
  • Pressures in the pulmonary circulatory system are much lower than those in the systemic circulatory system. The pressures in the pulmonary and systemic circulatory are compared in Figure 2.

Figure 2. Comparison of pressures (mm Hg) in the pulmonary and systemic circulations. Hydrostatic differences modify these. From JB West, Pulmonary Physiology The essentials, 7th ed.


II.Pulmonary vascular resistance - a measure of resistance to flow in the pulmonary vasculature system

The mean pressure in the pulmonary artery is about 15 mm Hg, the systolic and diastolic pressures are about 25 mm Hg and 8 mm Hg, respectively. Typically, mean pressure in the left atrium is about 5 mm Hg. This means that the entire cardiac output (5 liters/minute) moves across the pulmonary circuit with a net change in pressure (ΔP) of only about 10 mm Hg. The pulmonary vascular resistance (PVR) = 10 mm Hg/5L/min = 2 mm Hg/L/min. Comparable calculations for the systemic circuit show its resistance to be about 10 times greater.


What factors effect the pulmonary resistance?


The high distensibility, the small amount of vascular smooth muscle and the low intravascular pressures lead to a greater importance of “passive” extravascular effects on pulmonary resistance. These factors include lung volume, alveolar and intrapleural pressures, intravascular pressure, gravity and cardiac output.


  • Pressure-flow relationships – The relationship between pressure and flow is nonlinear. The pulmonary vascular resistance depends upon flow rate so unlike in a simple, rigid tube, there is no there is no single, characteristic resistance of the pulmonary vasculature.

A. Simple rigid tube B. Pulmonary vasculature

Figure 3. Pressure-flow relationships

Indeed, a paradoxical characteristic of the pulmonary vasculature is that higher flows are generally associated with lower resistances. Thus as cardiac output increases, pulmonary vascular resistance falls.


Why does PVR fall as flow increases? Two phenomena:


  1. Capillaries that were already open, now distend further.
  2. Capillaries that were formerly closed, now open (recruitment)

Figure 4. Recruitment (opening of previously closed vessels) and distension (increase in caliber of vessels). These are the two mechanisms for the decrease in pulmonary vascular resistance that occurs as vascular pressures are raised. From JB West, Pulmonary Physiology-The Essentials, 7th ed.


  • Alveolar and intrapleural pressure – Pulmonary vascular resistance depends on the transmural pressure gradient. As the transmural pressure gradient (pressure inside – pressure outside) decreases the diameter of the vessel decreases and vascular resistance increases.


  • Lung volume – Because the pulmonary vasculature is found largely within the lung, changes in lung volume have the potential to profoundly alter pulmonary vascular resistance. The interaction is complex, however, as different phenomena are important at lung volumes above and below FRC. The effects of changes in lung volume on pulmonary vascular resistance are shown in Figure 5.

Figure 5. The effects of lung volume on pulmonary vascular resistance. PVR is lowest near the FRC and increases at both high and low lung volumes because of the combined effects on the alveolar vessels. To achieve low lung volumes, one must generate positive intrapleural pressures so that the extraalveolar vessels are compressed, as see at left in the figure. From JB West, Pulmonary Physiology-The Essentials, 7th ed.


    • Above FRC


As lung volume increases above the FRC, the pulmonary vessels outside the alveoli are distended and their resistance falls. On the other hand, the septal capillaries in the alveolar walls are stretched so that their diameters are reduced. The net effect is an increase in overall pulmonary vascular resistance since the narrowing of septal capillaries is the dominant effect.


    • Below FRC


As lung volume decreases below FRC, the pulmonary vessels outside the alveoli tend to collapse as their walls are no longer being stretched by the surrounding lung tissue, leading to an increase in their resistance. The reduction in alveolar size leads to a reduction in the stretch of their walls. Although the resistance of the capillaries decreases, the overall effect is an increase in pulmonary vascular resistance since the increase in the extra-alveolar vessels is the dominant effect.


  • Gravity – In general, flow is greatest in the dependent portions of the lung (e.g. the bottom of the lung when the subject is seated) and least in the non-dependent regions (e.g. at the top of the lung in a seated subject).

Figure 6. Blood increases from top to bottom of lung.

Why should blood flow vary across the lung?


Need to consider regional (local) flow.


Note: The terms upstream and downstream refer to the direction of flow. Flow is from upstream to downstream during cardiac systole in the pulmonary vasculature.


Upstream – the inflow

Downstream- the outflow

Regional upstream pressure:


It has been observed that the gravitational gradient and other factors lead the local pulmonary arterial pressure to vary across the lung. Pressure is greatest in the most dependent regions of the lung. Pressure must be greater than local alveolar pressure in order for flow to occur.


Local downstream pressure:


While upstream pressure can easily be understood as local pulmonary arterial pressure, the analysis of the applicable downstream pressure is more complicated. Essentially, the downstream pressure can be either the pulmonary venous pressure OR the alveolar pressure, depending on local conditions.


The zones of the lung:


One way of modeling this arrangement is to conceive of the lung as being divided into 3 zones according to the applicable upstream and downstream pressures:

Figure 7. Zones of the lung.

Zone I

  • Alveolar pressure is greater than BOTH local pulmonary arterial and venous pressures.
  • Vessels are compressed and there is no flow.
  • Palv > Pa > Pv

Zone II

  • Pulmonary arterial pressure is greater than alveolar pressure.
  • The alveolar pressure is greater than the venous pressure, however, so that the downstream pressure is alveolar pressure.
  • This situation is termed a “vascular waterfall”; the flow is independent of the eventual venous pressure and depends only on the difference between pulmonary arterial pressure and alveolar pressure.
  • Pa > Palv > Pv

Zone III

  • Pulmonary artery pressure is greater than venous pressure and alveolar pressure.
  • The venous pressure is greater than the alveolar pressure so that flow depends on the arterio-venous pressure difference.
  • Pa > Pv > Palv


Under normal conditions, zone 1 does not occur. However, a patient on a positive-pressure ventilator with positive end-expiratory pressure may have substantial amounts of zone 1 because alveolar pressure is always positive. Similarly, after a hemorrhage, pulmonary blood flow is low and zone 1 makes a larger contribution.


  • Chemical factors that control the resistance of blood flow in the pulmonary circuit:


Hypoxic vasoconstriction: By far the most important modulator of the smooth muscle tone in the pulmonary arterioles is the partial pressure of O2 in the alveolus (PAO2). Interestingly, the smooth muscle of the pulmonary arterioles responds in an opposite manner than does smooth muscle of systemic arterioles, i.e., low PO2 produces constriction in pulmonary vessels. Also, the receptors that initiate this local (nerves not involved) vasoconstrictor response respond to PAO2 rather than the PO2 in the capillary blood. The mechanism for this response is not known, but may involve a hypoxia sensitive K+ channel. Note below that hypoxic vasoconstriction becomes more potent in a non-linear fashion with an inflection below 100 mm Hg (Figure 8).

    • Utility of hypoxic vasoconstriction in the pulmonary circuit


It limits blood flow through the lung of the fetus. Elevation of

PAO2 with the first breath greatly reduces resistance to blood flow through the lung.


It improves the matching of blood flow with ventilation: If a region of the lung is poorly ventilated, PAO2 in that region decreases. The resulting constriction decreases blood flow to that region. Blood that doesn’t go there will go to alveoli that are more adequately ventilated. (This topic will be covered again in the lecture on ventilation/perfusion ratios.)


The hypoxia that develops at high altitudes produces vasoconstriction throughout the entire pulmonary circuit, thus increasing total resistance to flow in the entire pulmonary circuit. The increased resistance leads to increased pressure in the pulmonary artery. The increased pressure leads to better perfusion of apical regions of the lung, thus improving the ventilation to perfusion ration of these regions and improves their capacity for gas exchange.


    • Consequences of chronic hypoxic vasoconstriction

The increased resistance increases work (afterload) for the right ventricle which in turn causes right ventricular hypertrophy. A hypertrophied right ventricle is more subject to failure than a normal right ventricle.

Over a period of years, the increased tone of the smooth muscle in the pulmonary arterioles leads to irreversible hypertrophy of their smooth muscle. At this point, the pulmonary hypertension is irreversible.


  • Other neurotransmitters and vasoactive substances:


Norepinephrine: although it will constrict pulmonary vessels, it is far less effective here than in the systemic circuit.


Histamine: Unlike the systemic circuit where it acts as a vasodilator, histamine causes vasoconstriction in the pulmonary circuit. Sertonin also causes constriction in the pulmonary circuit.


Nitric oxide (NO), also known as endothelium-derived-relaxing factor (EDRF) can counteract hypoxic-induced vasoconstriction.



  • III Water balance in the lung: In order for gas exchange to occur, it is essential that the alveolar surface be kept dry. Net fluid in the alveoli is determined by a balance between:


  1. Fluid filtration out of vessels
  2. Fluid reabsorption into vessels


Hydrostatic pressure - Pressure in vessels is higher than in interstium. Favors movement of fluid to the interstitum.


Oncotic pressure – Protein content higher in the vessels. Favors movement of fluid inwards toward the vessel.

Figure 9.

Starling Equation

When outwardly directed Starling forces increase sufficiently that lymph flow is no longer able to transport all of the filtered water, edema develops in the lung. For example, this can occur in response to pulmonary embolism, mitral stenosis or left ventricular failure, all of which will raise net filtration pressure in the pulmonary capillaries. Edema initially develops in the lung interstitium; it then develops in the perivascular and peribronchial spaces. If filtration forces exceed reabsorptive forces for long enough, the fluid starts to fill alveoli (Fluid accumulates first in basal alveoli. Why?). Gas diffusion can not occur in fluid-filled alveoli. If still perfused, these unventilated alveoli become right to left shunts, i.e., venous blood moves through them without gaining any O2.


  • IV Other functions of the pulmonary circulation:


    • Reservoir: When you suddenly lie down after standing, quite a bit of venous

formerly in the legs drains to the right atrium. The right ventricle pumps the extra blood into the lung, but not all of it immediately moves to the left ventricle, i.e. some of it is “stored” in the lung. This prevents cardiac output from increasing excessively as one goes from an upright to a lying-down position. On the other hand, when one goes from a lying-down to an upright position (and blood now pools in the legs), the “stored” blood in the lung now flows into the left atrium helping to maintain cardiac output long enough for baroreceptor reflexes to initiate other compensatory mechanisms.

    • Filter: Clots that form in systemic veins in response to injury must go through the lungs before reaching the left heart. The small pulmonary vessels filter out these clots. They are then broken down and absorbed. Were this not the case, small clots would cause coronary or cerebral thrombosus (heart attacks and strokes) much more often.
    • Metabolic functions of the lung:
  1. The type-2 alveolar cells make pulmonary surfactant. Pulmonary surfactant (covered in a later lecture) is essential for normal compliance of the lung.
  2. In the lung, converting enzyme, converts inactive Angiotensin I to active Angiotensin II. Converting enzyme also converts active bradykinin to an inactive metabolite.
  3. The lung makes immunglobulin A, which provides a defense mechansim against pulmonary infections.
  4. The upper airways secrete mucus which is essential for removal of inhaled particles.
  5. The lung removes serotonin from the blood; some of this serotonin may be transferred to platelets.
  6. Prostaglandin E2 is produced by the lung of the fetus, wherein it serves as a smooth muscle relaxant keeping the ductus arteriosus open during fetal life. The elevation of pulmonary and systemic PO2 which occurs when the newborn child begins to breathe causes contraction of the smooth muscle of the ductus arteriosus causing the ductus to close. If the ductus fails to close, inhibitors of prostaglandin synthesis (indomethacin) can be adminstered to facilitate closure of the ductus.

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