Pulmonary Circulation and Ventilation-Perfusion Ratio

Introduction

Pulmonary circulation is a low-resistance vascular system specially adapted to accommodate the entire cardiac output with minimal pressure changes. Efficient gas exchange also depends on optimal matching between alveolar ventilation and pulmonary blood flow, which varies significantly from the apex to the base of the lungs.

Pulmonary Circulation

• Pulmonary circulation receives the entire cardiac output pumped by the right ventricle, which is equal to the blood flow through the systemic circulation.
• Despite its smaller vascular capacity, the pulmonary circulation accommodates this large blood flow efficiently.
• Pulmonary blood vessels are highly distensible and offer relatively low vascular resistance.
• Consequently, pulmonary arterial pressure remains low even when blood flow increases.
• In contrast, the systemic circulation functions as a high-pressure system because systemic vascular resistance is much greater.
• Total pulmonary vascular resistance is normally approximately one-tenth of systemic vascular resistance, making the lungs a low-pressure, low-resistance circulation.

Functional Organization

• The pulmonary arteries branch in parallel with the bronchial tree, ensuring efficient delivery of blood to ventilated lung regions.
• Pulmonary arterioles divide extensively to form a dense capillary network around each alveolus.
• Each alveolus is surrounded by a capillary basket, providing a large surface area for gas exchange.
• Pulmonary capillaries are highly interconnected through numerous anastomoses, facilitating uniform blood distribution.
• Blood from alveolar capillaries drains into pulmonary venules and subsequently into pulmonary veins.
• Blood contained within the pulmonary vasculature contributes approximately 40 percent of the total lung weight.

Functions of Pulmonary Circulation

• The principal function of pulmonary circulation is to transport deoxygenated blood from the right ventricle to the lungs for gas exchange.
• Within pulmonary capillaries, carbon dioxide diffuses from blood into the alveoli, while oxygen diffuses from alveolar air into the blood.
• The pulmonary vasculature also functions as an important biological filter.
• Small thrombi, air bubbles, and embolic particles originating in the venous circulation are trapped within pulmonary vessels, thereby protecting the systemic circulation.
• Pulmonary endothelial cells possess fibrinolytic activity and contribute to the breakdown of intravascular thrombi.
• The lungs perform several metabolic functions by modifying circulating vasoactive substances.
• Angiotensin-converting enzyme located on pulmonary capillary endothelium converts angiotensin I to angiotensin II.
• Pulmonary endothelial cells also inactivate or remove substances such as bradykinin, serotonin, prostaglandins, and norepinephrine from the circulation.
• In addition, the pulmonary circulation serves as a blood reservoir, normally containing approximately 500 milliliters of blood that can be mobilized when required.

Special Features of Pulmonary Circulation

• Pulmonary circulation is a low-pressure, low-resistance vascular system specialized for efficient gas exchange.
• The normal mean pulmonary arterial pressure is approximately 15 millimeters of mercury, which is considerably lower than systemic arterial pressure.
• Pulmonary arteries possess thin walls and contain relatively little smooth muscle.
• These structural features make pulmonary arteries highly compliant, allowing them to accommodate large changes in blood volume with minimal increases in pressure.
• Pulmonary arteries are generally shorter and wider than systemic arteries of comparable size, further reducing vascular resistance.
• Owing to their high compliance, pulmonary vessels can accommodate transient increases in venous return, such as when a person moves from standing to the recumbent position.
• Pulmonary arterioles are also thin walled and contain less smooth muscle than systemic arterioles.
• Consequently, their vasoconstrictor capacity is relatively limited.
• Pulmonary veins are highly compliant and serve as an important blood reservoir within the lungs.
• The pulmonary capillary arrangement differs from that in systemic tissues.
• Pulmonary capillaries form an extensive sheet-like network within the alveolar walls, creating a large surface area for gas exchange.
• Blood therefore flows as a thin film adjacent to alveolar air, facilitating rapid diffusion of respiratory gases.
• The walls of pulmonary capillaries are extremely thin and may collapse if alveolar pressure exceeds capillary pressure.
• Changes in pulmonary venous and left atrial pressures strongly influence pulmonary fluid balance and gas exchange.
• Pulmonary capillary wedge pressure provides an indirect estimate of left atrial pressure.
• This pressure is measured using a balloon-tipped catheter advanced through the right side of the heart into a small pulmonary artery.
• When the catheter balloon occludes the vessel, the measured pressure closely reflects left atrial pressure under normal conditions.
• Pulmonary vascular resistance is approximately one-tenth of systemic vascular resistance.
• The low resistance results primarily from the short, wide, and highly compliant pulmonary resistance vessels.
• In addition, resting sympathetic vasoconstrictor tone in pulmonary arterioles is minimal, so most vessels remain relatively dilated.
• A distinctive feature of pulmonary circulation is that pulmonary vascular resistance decreases when pulmonary blood flow increases.
• This response enables the lungs to accommodate large increases in cardiac output during exercise without marked elevation of pulmonary arterial pressure.
• The principal mechanism responsible is capillary recruitment, in which previously underperfused or collapsed capillaries open as pulmonary arterial pressure rises.
• Recruitment increases the number of parallel vascular channels, thereby reducing overall vascular resistance.
• A second mechanism is capillary distension, in which existing vessels enlarge in response to increased intravascular pressure.
• Capillary recruitment and distension together ensure efficient perfusion and maintain optimal conditions for pulmonary gas exchange during increased circulatory demand.

Physiological Significance of Low PVR

• A decrease in pulmonary vascular resistance during increased cardiac output facilitates efficient pulmonary gas exchange.
• Reduced resistance allows blood to traverse a larger number of pulmonary capillaries, maintaining adequate transit time for oxygen uptake and carbon dioxide elimination.
• Capillary distension and recruitment increase the effective surface area available for diffusion across the alveolar-capillary membrane.
• These adaptations enhance the transfer of respiratory gases, particularly during exercise.
• Lower pulmonary vascular resistance also limits excessive rises in pulmonary capillary pressure.
• By preventing marked elevations in capillary hydrostatic pressure, the lungs are protected from pulmonary edema during periods of increased blood flow.

Pulmonary Blood Flow

• Approximately 500 milliliters of blood are present within the pulmonary circulation at any given time, representing nearly 10 percent of the total blood volume.
• Of this volume, about 150 milliliters are contained in pulmonary arteries, 80 milliliters in pulmonary capillaries, and 270 milliliters in pulmonary veins.

Distribution of Pulmonary Blood Flow

• In the upright position, pulmonary blood flow is not uniformly distributed throughout the lungs.
• Blood flow is lowest at the lung apex and progressively increases toward the base because of gravity.

H4: Factors Affecting Pulmonary Blood Flow

Major factors influencing pulmonary blood flow include pulmonary vascular resistance, gravity, alveolar pressure, and the pressure gradient between pulmonary arteries and veins.

Pulmonary Vascular Resistance

Pulmonary vascular resistance is influenced by lung volume, vasoactive substances, and alveolar oxygen tension.

1. Lung Volumes

• Pulmonary blood vessels are functionally classified into alveolar vessels and extra-alveolar vessels.
• Alveolar vessels include pulmonary capillaries and small vessels located within alveolar walls.
• Extra-alveolar vessels comprise larger pulmonary arteries and veins situated outside the alveoli.
• Extra-alveolar vessels are primarily influenced by pleural pressure, whereas alveolar vessels are affected mainly by alveolar pressure.

High Lung Volumes

• At high lung volumes, pleural pressure becomes more negative, increasing the transmural pressure across extra-alveolar vessels and causing their distension.
• Simultaneously, expansion of the alveoli compresses alveolar vessels, increasing their resistance.

Low Lung Volumes

• At low lung volumes, pleural pressure becomes less negative, reducing radial traction on extra-alveolar vessels and promoting their narrowing or collapse.
• Consequently, pulmonary vascular resistance increases at both very high and very low lung volumes.
• Pulmonary vascular resistance is lowest near the functional residual capacity, where the opposing effects on alveolar and extra-alveolar vessels are balanced.

2. Hormones

• Several hormones and mediators regulate pulmonary vascular tone.
• Serotonin, norepinephrine, histamine, thromboxane A₂, and leukotrienes produce pulmonary vasoconstriction and increase vascular resistance.
• Acetylcholine, adenosine, prostacyclin, and β₂-adrenergic agonists cause vasodilation and reduce resistance.

3. Oxygen tension

Hypoxia is a unique stimulus in pulmonary circulation, causing vasoconstriction and thereby increasing pulmonary vascular resistance.

Effects of Gravity

• Gravity has a major influence on the distribution of pulmonary blood flow in the upright position.
• Because the lung apex lies above the level of the heart and the base lies below it, hydrostatic pressure varies throughout the lung.
• Pulmonary arterial and venous pressures progressively decrease from the base toward the apex.
• For every centimeter above the heart, vascular hydrostatic pressure decreases by approximately 0.74 millimeters of mercury.
• Conversely, pressure increases by approximately 0.74 millimeters of mercury for every centimeter below the heart.
• Consequently, pulmonary perfusion is lowest at the apex and greatest at the base of the lungs.
• These gravity-dependent differences in perfusion significantly influence the ventilation-perfusion ratio.
• Based on the relationship between alveolar pressure and vascular pressures, the upright lung is functionally divided into three zones.

Upper Zone

• In the uppermost lung regions, alveolar pressure may equal or exceed capillary pressure.
• Capillary perfusion is therefore minimal, and some capillaries may collapse.
• Ventilation exceeds perfusion in this region, resulting in a high ventilation-perfusion ratio.
• The upper zone behaves physiologically as an area of increased alveolar dead space.
• In healthy individuals, Zone 1 is usually absent or occupies only a very small portion of the lung.
• Zone 1 enlarges when pulmonary arterial pressure decreases or alveolar pressure rises excessively.
• Conditions such as severe hemorrhage, hypovolemia, or positive-pressure ventilation may increase the extent of Zone 1.

Middle Zone

• In the middle region, pulmonary arterial pressure exceeds alveolar pressure, but alveolar pressure may exceed pulmonary venous pressure.
• Blood flow occurs only when arterial pressure is greater than alveolar pressure.
• Consequently, perfusion depends primarily on the difference between pulmonary arterial pressure and alveolar pressure.
• Blood flow in this region demonstrates the waterfall effect, in which downstream venous pressure has little influence on flow.
• Zone 2 occupies a substantial portion of the normal upright lung.

Lower Zone

• In the lower lung regions, pulmonary arterial and venous pressures both exceed alveolar pressure throughout the cardiac cycle.
• Blood flow is therefore determined mainly by the arteriovenous pressure gradient.
• Because vascular pressures are highest in this region, pulmonary capillaries become distended and numerous capillaries are recruited.
• As a result, perfusion is maximal at the lung base.
• Although ventilation also increases toward the base, the increase in perfusion is proportionally greater, producing a relatively lower ventilation-perfusion ratio in this region.

Effects of Alveolar Pressure

• Alveolar pressure varies with changes in lung volume and influences pulmonary vascular caliber.
• Increased alveolar pressure can compress alveolar capillaries and reduce pulmonary blood flow.

Arterio-venous Pressure Gradient

• Pulmonary perfusion is also determined by the arteriovenous pressure gradient.
• Changes in alveolar pressure alter this pressure gradient and thereby modify pulmonary blood flow.

Regulation of Pulmonary Blood Flow

Pulmonary blood flow is regulated by both active and passive mechanisms.

Active Factors

Active regulatory factors include neural, hormonal, and chemical influences on pulmonary vascular tone.

Neural Regulation

• Although pulmonary vessels receive abundant sympathetic innervation, autonomic activity exerts only a limited effect under normal resting conditions.
• This minimal influence is due to the very low resting sympathetic tone in the pulmonary circulation.
• Sympathetic stimulation produces mild vasoconstriction, whereas parasympathetic stimulation causes mild vasodilation of pulmonary vessels.

Table 106.1: Vasoconstrictors and vasodilators of pulmonary circulation.

Agents Increasing Pulmonary Vascular Tone (Vasoconstriction)	Agents Decreasing Pulmonary Vascular Tone (Vasodilation)
Catecholamines acting on α₁ receptors	Catecholamines acting on α₂ and β₂ receptors†
Purinergic stimulation via P2X receptors	Acetylcholine acting on M3 receptors†
Tachykinins acting on NK₂ receptors	Purinergic stimulation via P2Y receptors†
Adenosine acting on A₁ receptors	Adenosine acting on A₂ receptors
Angiotensin II acting on AT₁ receptors	Bradykinin acting on B₁ and B₂ receptors†
Endothelin acting on ETA receptors	Endothelin acting on ETB receptors†
Serotonin acting on 5-HT₁ receptors	Vasoactive intestinal peptide, calcitonin gene-related peptide, and atrial natriuretic peptide
Thromboxane acting on TP receptors	Histamine (H₁, H₂), serotonin (5-HT₁C), and vasopressin (V₁ receptors)†

Endothelium-dependent vasodilator responses.

Hormonal Regulation

• Hormonal regulation plays an important role in controlling pulmonary vascular tone and blood flow.
• Serotonin, norepinephrine, endothelin, angiotensin II, thromboxane A₂, and leukotrienes are major pulmonary vasoconstrictors that increase pulmonary vascular resistance.
• Adenosine, acetylcholine, prostacyclin, bradykinin, and nitric oxide produce pulmonary vasodilation and enhance blood flow.

Chemical Regulation

• A distinctive feature of pulmonary circulation is that alveolar hypoxia causes constriction of small pulmonary arteries.
• This response diverts blood away from poorly ventilated alveoli toward better-ventilated regions, thereby improving ventilation-perfusion matching.
• Hypoxia-induced pulmonary vasoconstriction is believed to involve inhibition of potassium channels, membrane depolarization, opening of voltage-gated calcium channels, and increased intracellular calcium concentration.
• Elevated carbon dioxide levels and decreased blood pH further augment this vasoconstrictor response.

Passive Factors

Passive factors regulating pulmonary blood flow include cardiac output, gravity, and lung volume. Increased cardiac output enhances pulmonary perfusion.

Filtration Across Pulmonary Capillaries

• Movement of fluid across pulmonary capillaries is governed primarily by Starling forces, similar to those operating in systemic capillaries.
• Fluid exchange depends on the balance between hydrostatic pressure and colloid osmotic pressure across the capillary wall.
• In the lungs, alveolar surface tension and alveolar pressure also influence fluid movement.
• Pulmonary capillary hydrostatic pressure is relatively low, averaging approximately 8 to 10 millimeters of mercury.
• Plasma colloid osmotic pressure is approximately 25 millimeters of mercury, favoring reabsorption of fluid into the capillaries.
• The low hydrostatic pressure normally protects the lungs from excessive fluid accumulation.
• Alveolar surface tension tends to pull alveolar walls inward, lowering interstitial pressure and promoting filtration of fluid into the pulmonary interstitium.
• In contrast, alveolar pressure compresses the interstitial space, increasing interstitial pressure and thereby opposing filtration.
• The combined effect of these forces results in the continuous filtration of a small amount of fluid from pulmonary capillaries into the interstitial space.
• Excess interstitial fluid is normally removed efficiently by the pulmonary lymphatic system.
• Pulmonary lymphatic vessels are particularly abundant around bronchi and terminal bronchioles, facilitating drainage of fluid from peribronchial and perivascular tissues.
• Effective lymphatic drainage is essential for maintaining dry alveoli and preserving optimal gas exchange.

Pulmonary Edema

• Pulmonary edema is characterized by excessive accumulation of fluid within the pulmonary interstitium and alveoli, impairing gas exchange.
• The most common cause is an increase in pulmonary capillary hydrostatic pressure.
• Elevated pulmonary venous pressure in conditions such as left ventricular failure or mitral valve stenosis promotes fluid filtration into lung tissues.
• Increased alveolar surface tension, particularly due to surfactant deficiency, favors fluid movement into the interstitial space.
• Surfactant deficiency contributes to pulmonary edema in disorders such as acute respiratory distress syndrome.
• A reduction in plasma colloid osmotic pressure, as seen in severe hypoproteinemia, also promotes pulmonary edema.
• Increased capillary permeability resulting from pulmonary vascular injury permits excessive leakage of fluid and proteins into the lungs.
• Pulmonary vascular injury may occur because of oxidant exposure, severe inflammatory responses, sepsis, or neurogenic injury following head trauma.

Physiological Basis of Treatment of Pulmonary Edema

• The principal goal in treating pulmonary edema is to reduce pulmonary capillary hydrostatic pressure and improve gas exchange.
• Diuretics decrease intravascular volume, thereby reducing pulmonary venous pressure.
• Positive inotropic agents, such as digitalis, improve left ventricular performance in selected patients with heart failure.
• Systemic vasodilators reduce cardiac preload and afterload, lowering pulmonary vascular congestion.

Drowning

Fresh-Water Drowning

• Fresh-water drowning involves aspiration of hypotonic water into the lungs.
• Aspirated fresh water may be absorbed across the alveolar-capillary membrane into the circulation.
• Excessive water absorption can cause hemodilution and hemolysis of erythrocytes.
• Hemolysis may lead to electrolyte disturbances, including hyperkalemia, which can precipitate cardiac arrhythmias.
• Severe hypoxemia resulting from impaired gas exchange is a major contributor to cardiac arrest and death.

Salt-Water Drowning

• In salt-water drowning, hypertonic seawater draws fluid from pulmonary capillaries into the alveoli.
• This process produces pulmonary edema, markedly impairing oxygen exchange.
• Death in salt-water drowning usually results from profound hypoxemia and asphyxia secondary to respiratory failure.

Ventilation-Perfusion Ratio

• The ventilation-perfusion ratio describes the relationship between alveolar ventilation and pulmonary blood flow.
• Efficient pulmonary gas exchange requires close matching between ventilation and perfusion.
• In healthy individuals, minor mismatching normally exists, so a small proportion of blood is not fully oxygenated.
• The ventilation-perfusion ratio is expressed as alveolar ventilation divided by pulmonary perfusion (V̇A/Q̇ ratio).
• At rest, average alveolar ventilation is approximately 4 liters per minute, whereas pulmonary blood flow is about 5 liters per minute.
• Therefore, the normal overall ventilation-perfusion ratio is approximately 0.8.
• Gravity produces regional differences in both ventilation and perfusion within the lungs.
• In the upright position, the lung bases receive greater ventilation and greater blood flow than the apices.
• However, the increase in perfusion toward the lung base is proportionally greater than the increase in ventilation.
• Consequently, the ventilation-perfusion ratio is lower at the base of the lungs.
• At the lung apex, ventilation exceeds perfusion proportionally, resulting in a higher ventilation-perfusion ratio.
• Pulmonary blood flow varies approximately fivefold from apex to base, whereas ventilation varies only about twofold.
• As a result, the V̇A/Q̇ ratio is approximately 0.6 at the lung base and may increase to nearly 3.0 at the apex.
• These regional differences contribute to physiological variations in alveolar and arterial gas composition.

Importance of VA/Q ratio

Physiological Importance

• The ventilation-perfusion ratio is a major determinant of efficient pulmonary gas exchange.
• A high ventilation-perfusion ratio at the lung apex indicates that ventilation exceeds perfusion proportionally.
• Consequently, alveolar oxygen partial pressure is relatively high, whereas alveolar carbon dioxide partial pressure is relatively low in apical regions.
• At the lung base, perfusion increases more than ventilation, resulting in a lower ventilation-perfusion ratio.
• Therefore, blood leaving the basal regions is slightly less oxygenated than blood from the apex.

Clinical Importance

• Regional differences in ventilation-perfusion matching influence the distribution of certain pulmonary diseases.
• Pulmonary tuberculosis commonly affects the lung apex because the higher alveolar oxygen tension in this region favors the growth of Mycobacterium tuberculosis.

Effects of Change in V A/Q·Ratio

Decreased V·A/Q Ratio

• A decreased ventilation-perfusion ratio occurs when alveolar ventilation is reduced relative to pulmonary perfusion.
• In this situation, alveolar oxygen partial pressure decreases, whereas alveolar carbon dioxide partial pressure increases.

Increased V·A/Q· Ratio

• An increased ventilation-perfusion ratio occurs when perfusion decreases relative to ventilation.
• Reduced blood flow delivers less carbon dioxide to the alveoli and extracts less oxygen from alveolar air.
• Consequently, alveolar carbon dioxide partial pressure decreases, while alveolar oxygen partial pressure increases.

Venous Admixture and Physiologic Shunt

• Venous admixture refers to the mixing of deoxygenated blood with oxygenated arterial blood, thereby reducing arterial oxygen content.
• Wasted perfusion occurs when blood passes through the lungs without becoming fully oxygenated.
• Venous admixture may result from a shunt or from regions with a low ventilation-perfusion ratio.

Shunt

A shunt is a pathway through which blood bypasses ventilated alveoli and therefore does not participate in gas exchange.

Anatomical Shunt

• In an anatomical shunt, blood bypasses the lungs because of a structural abnormality.
• Examples include right-to-left intracardiac shunts associated with atrial or ventricular septal defects and abnormal connections between pulmonary arteries and veins.

Physiological Shunt

• A physiological shunt occurs when deoxygenated blood enters the systemic arterial circulation under normal conditions.
• The major physiological shunt arises from bronchial venous blood draining into the pulmonary veins.
• Small physiological shunts are normally present and contribute to the slight difference between alveolar and arterial oxygen partial pressures.

Low Ventilation-Perfusion Ratio

• A low ventilation-perfusion ratio occurs when alveolar ventilation is inadequate relative to pulmonary blood flow.
• Under normal conditions, lower ventilation-perfusion ratios are present at the lung bases.
• Partial airway obstruction may also produce localized hypoventilation.
• Blood passing through poorly ventilated alveoli remains incompletely oxygenated, resulting in venous admixture and a reduction in arterial oxygen tension.

Bronchial Circulation

• Bronchial circulation supplies oxygenated blood to the conducting airways, supporting tissues, visceral pleura, and larger pulmonary blood vessels.
• This circulation nourishes the trachea, bronchi, and bronchioles but does not significantly supply the respiratory bronchioles or alveoli.
• Venous drainage from the bronchial circulation occurs through bronchial veins and bronchopulmonary venous channels.
• Some bronchial venous blood drains into the pulmonary veins, contributing to the normal physiological shunt.
• Bronchial blood flow normally accounts for approximately 1 percent of cardiac output.
• In chronic inflammatory airway diseases, such as chronic bronchitis, bronchial blood flow may increase substantially.

Physiological Importance

• Bronchial arteries arise from the systemic circulation; therefore, their pressure approximates aortic pressure.
• Consequently, bronchial vascular resistance is considerably higher than pulmonary vascular resistance.
• A unique feature of the bronchial circulation is its capacity for angiogenesis, enabling the formation of collateral blood vessels.
• These collateral vessels help maintain the viability of lung tissue when pulmonary arterial blood flow is compromised by embolism or vascular obstruction.