Ventilation/perfusion inequality


  • Gas exchange is optimized when pulmonary perfusion (Q) and alveolar ventilation (V A ) are tightly matched. The fractal design of the lung and gravitational effects on the flow of air and blood affect V A /Q matching.

  • Gravity increases pulmonary blood flow and ventilation to the base of the lung. Perfusion is affected more by gravitational forces than ventilation but is of secondary importance in Q and V A .

  • The primary V A /Q abnormality in pediatric acute respiratory distress syndrome (PARDS) is intrapulmonary shunt.

  • Ventilation/perfusion ratios less than 1 are responsible for hypoxemia in asthmatics, but no correlation exists between V A /Q mismatch and the degree of small airway obstruction.

  • During mechanical ventilation, positive end-expiratory pressure decreases the proportion of shunt in PARDS. However, at high levels, it increases dead space ventilation and hypercarbia.

  • Prone position improves V A /Q matching by more evenly distributing V A and Q. It also produces more uniform distribution of stress and strain of lung tissue.

The lung functions primarily to exchange oxygen (O 2 ) and carbon dioxide between inspired air and blood. Efficient gas exchange requires close matching of regional ventilation and perfusion. The lung is influenced by internal and external factors that affect ventilation/perfusion (V A /Q) relationships, including gravity and the fractal design of the pulmonary blood vessels and airways. Ventilation is also affected by the frequency, duration, and rate of breathing. Early studies supported the concept that vertical gradients increased ventilation and perfusion in the lung, yielding close V A /Q matching. Newer studies demonstrated much greater heterogeneity in perfusion and ventilation in isogravitational planes, indicating that lung structure also contributes to matching perfusion and ventilation. Under normal conditions, ventilation and perfusion are closely matched. Ventilation/perfusion mismatch denotes a wide spectrum of conditions in which V A /Q deviates from a ratio of 1. At one extreme, intrapulmonary shunt refers to lung regions that receive blood flow but no ventilation (V A /Q = 0) and may be due to many pathologic conditions (e.g., complete atelectasis, consolidated lobar pneumonia). At the other extreme, dead space is where ventilation is matched by no blood flow (e.g., complete occlusion behind a pulmonary embolism). Hypoxemia is caused by areas of lung with V A /Q ratios greater than 1. Intrapulmonary shunt has been separated from areas of low V A /Q as a category because of the lack of response to increasing fractional inspired oxygen concentration (F io 2 ).

Lung diseases commonly produce abnormalities in functional residual capacity (FRC) and closing capacity, which distort normal V A /Q matching ( Table 45.1 ). Lung units that are poorly ventilated in relation to blood flow (V A /Q < 1) produce desaturated blood with low oxygen content. Units with high V A /Q ratios are unable to compensate because the blood leaving these areas has only a slightly higher oxygen content compared with normal V A /Q regions due to the sigmoid shape of the hemoglobin oxygen dissociation curve ( Fig. 45.1 ).

TABLE 45.1

Causes of Hypoxemia

Intrapulmonary Factors Extrapulmonary Factors
Primary Primary
Ventilation/perfusion mismatch (low V/Q)
Alveolar-end capillary diffusion limitation
Decreased minute ventilation
Decreased F io 2
Decreased cardiac output
Secondary Decreased P 50
Decreased hemoglobin concentration

P , pressure; F io 2, fractional inspired oxygen concentration.

• Fig. 45.1

Gas exchange in a single lung unit. Changes in P o 2 , P co 2 , and end-capillary O 2 content in a lung unit as its ventilation/perfusion ratio is increased from shunt (V/Q = 0) to dead space (V/Q = ∞). Hemoglobin concentration is 14.8 g/dL.

The alveolar gas equation helps to explain the pathophysiology of abnormal gas exchange by providing information on alveolar oxygen tension. According to the Fick equation, under steady-state conditions, the quantity of O 2 taken up by the lungs equals the amount of O 2 removed from inhaled air:

O 2 = V A (F io 2 – F ao 2 )

where O 2 is oxygen consumption, F io 2 is the fraction of inspired O 2 , and F ao 2 is the fraction of alveolar O 2 . This equation can be rearranged to read:

F ao 2 = F io 2 – O 2 /V A

Then, by changing the fraction of gases to their partial pressures, the equation takes the following form:

P ao 2 = P io 2 – (O 2 /V A )(P B – 47 mm Hg)

where P io 2 is the inspired P o 2 and P B is barometric pressure.

The concept underlying this equation is that alveolar oxygen level (P ao 2 ) is the difference between inspired oxygen (P io 2 ) and the amount taken up by the pulmonary capillaries [(O 2 /V A )(P B – 47 mm Hg)]. The ratio O 2 /V A can be estimated from a surrogate for the ratio between O 2 and V A . By using P co 2 in arterial blood as an estimate of alveolar CO 2 , CO 2 /V A as an estimator of F aco 2 , and the respiratory quotient R = CO 2 /O 2 , the second term of Eq. 45.3 can be estimated by P aco 2 /R. The alveolar gas equation can then be derived as follows:

P ao 2 = F io 2 × (P B – 47 mm Hg) – (CO 2 /R/V A ) × (P B – 47 mm Hg)

P ao 2 = F io 2 × (P B – 47 mm Hg) – (F aco 2 /R) × (P B – 47 mm Hg)

P ao 2 = F io 2 × (P B – 47 mm Hg) – (P aco 2 /R)

According to this equation, P ao 2 may be decreased by increases in the P aco 2 or by decreases in the atmospheric pressure and R.

Distribution of ventilation

Regional lung ventilation is influenced by many factors—gravity, posture, pathology, and experimental technique. Gravity has been considered paramount because it creates variation in pleural pressure from the lung apex to the base, imposing a globular shape on the lung. Pleural pressure is more negative at the apex of the lung compared with the base, increasing approximately 0.25 cm H 2 O per centimeter of vertical distance toward the base. Consequently, transpulmonary pressure is greater at the apex, and apical alveoli are large at the upper end of the normal pressure-volume curve and distend less for a given pressure change (lower compliance). In the upright, spontaneously breathing human, maximal gas distribution occurs at the base, progressively diminishing toward the lung apex. , This gradient also exists when inhalation occurs in the supine position, although to a lesser degree.

Ventilation heterogeneity does not depend solely on gravitational influences; it also depends on the variable compliance and resistance to airflow found across the lung. The time constant (the product of resistance and compliance) is the time required for inflation to 63% of final lung volume. A lung unit with a slow time constant fills and empties more slowly than one with a fast time constant. In lung disease, resistance and compliance are often altered, producing lung segments with different time constants, such that gas distribution will be determined in part by the rate, duration, and frequency of breathing.

Distribution of perfusion

The pulmonary circulation is a low-pressure circuit with a mean pulmonary artery pressure (P PA ) of approximately 15 mm Hg, compared with mean systemic pressure on the order of 100 mm Hg. According to the classical model of lung perfusion, gravity affects pulmonary blood flow (PBF) in a similar fashion to ventilation but to a greater extent. The P PA decreases by 1 cm H 2 O per centimeter of vertical distance up the lung; thus, the driving pressure rapidly drops with minimal blood flow to the apices. In the erect human, PBF progressively increases from apex to base.

The three-zone model of PBF has been widely used to explain the heterogeneity of perfusion within the lung ( Fig. 45.2 ). Three variables comprise the components of this model: pulmonary arterial (P PA ), alveolar (P A ), and pulmonary venous (P V ) pressures. PBF within the lung zones depends on the relative magnitudes of these pressures within each zone. In the upright subject, zone 1 is the most cephalad and zone 3 the most caudad. In zone 1, P A > P PA > Pv, and the region has negligible blood flow, as high alveolar pressure is believed to compress collapsible capillaries. This region is one of high V A /Q ratios or dead space ventilation. Zone 1 conditions are rare except in cases of diminished PBF (e.g., hypotension or cardiac failure) or increased P A encountered during positive-pressure ventilation. Zone 2 is found in the middle of the lung, where P PA > P A > P V . PBF is determined by the difference between P PA and P A . Venous pressure does not influence the flow rate. Blood flow progressively increases with descent through this zone as P PA increases, whereas P A remains relatively constant. The V A /Q ratio decreases when moving from the rostral to caudal lung. The most caudal lung region is zone 3, where P PA > P V > P A . Here, the arteriovenous pressure gradient (P PA – P V ) determines PBF. V A /Q ratios are the lowest in this region, where perfusion is generally greater than ventilation.

• Fig. 45.2

Normal distribution of pulmonary blood flow: gravitational model. According to the model, the gravitational driving force for pulmonary blood flow increases down the lung. At the apex (zone 1), flow is absent as alveolar pressure (P A ) exceeds pulmonary artery (P PA ) and pulmonary venous (P V ) pressures. In zone 2, flow is determined by the driving pressure (P PA – P A ). Flow is constant and maximal in zone 3 because both P PA and P V exceed P A where the driving pressure is P PA – P V .

The lung can be considered to have a zone 4 region in the most dependent areas of lung when transudated pulmonary interstitial fluid increases interstitial pressures, thereby reducing blood flow. Zone 4 can be considered a Starling resistor, where P PA > P interstitial > P V > P A and blood flow is determined by the difference between pulmonary artery and interstitial pressures. This effect is exaggerated as lung volume diminishes from total lung capacity to residual volume.

PBF in immature animals differs in several important ways from that of adult animals. The immature pulmonary vascular bed appears to be fully recruited, with no contribution of Starling resistors in the pulmonary circulation during exposure to acute or chronic hypoxia. , Furthermore, neonatal piglets show a relative hypoxemia with an increased dispersion of PBF.

Fractal model of pulmonary blood flow and ventilation

PBF possesses greater heterogeneity than described in the gravitational model alone. Isogravitational PBF was shown to be nearly as heterogeneous as that of the entire lung ( Fig. 45.3 ). Rather than being randomly distributed, PBF was similar within neighboring regions. High-flow regions bordered other high-flow regions while low-flow regions abutted other low-flow regions. The distribution of PBF was shown to be independent of the scale of measurement, suggesting a fractal nature of PBF.

• Fig. 45.3

Isogravitational heterogeneity of pulmonary blood flow. Reconstruction of transverse and sagittal plane from a single baboon animal during upright posture. Each square depicts location and relative blood flow to a piece of lung in a given plane. Heterogeneity of blood flow is present in isogravitational planes. Flow is not random; rather, neighboring pieces tend to have similar magnitudes of flow. Cephalad-caudad (gravitational) gradient is apparent in the sagittal section.

A fractal structure has a characteristic form that remains constant over a magnitude of scales ( Fig. 45.4 ). Both the bronchial tree and pulmonary vascular beds have a fractal design. , In animal models and in humans under conditions of microgravity, the contribution of gravity to overall perfusion heterogeneity was of secondary importance. Blood flow in the lung shows a gradient from the hilum to the periphery, with increased flow to the dorsal compared to ventral region regardless of position. The asymmetry of flow at pulmonary artery branches accounts for the heterogeneity of flow within isogravitational planes. In other words, regions that share a parent or grandparent branch have more similar flows than do branches that are separated by a greater distance. This fractal pattern extends to the subacinar level.

• Fig. 45.4

Fractal structures. (A) This curve is produced by a simple iterative transformation beginning with a straight line. At each step, the middle third of all lines is replaced with two segments, one-third length of the line, forming part of an equilateral triangle. An infinite number of iterations can be performed. Thus, as increasing magnification reveals more detail, the overall appearance of the new segment remains similar to that of the previous segment. (B) The pulmonary vascular (and bronchial) tree is a repetitive pattern of dichotomous branches that become progressively smaller and fill a predetermined area.

The close correlation between regional ventilation and perfusion suggests that ventilation has spatial characteristics similar to perfusion. Fractals possess a large area-to-volume ratio, ensuring that all alveoli are serviced by capillaries efficiently and that gas and substrate exchange irrespective of an organism’s size. The innate structure of the lung itself appears to underlie the precision of V A /Q matching. There is a close association of the developing bronchial tree and pulmonary arterial tree during organogenesis.

Basal pulmonary vascular tone is minimal, suggesting that vasoregulation is of minor importance for maintaining close V A /Q matching normally. Passive matching of perfusion and ventilation by pulmonary structure suggests an optimally engineered system because it requires no active feedback mechanism function normally ( Fig. 45.5 ). A fractal design has several additional advantages in addition to V A /Q matching on a structural level. Fractals ensure minimal energy expenditure to deliver substrate due to lower hydrodynamic resistance. There is conservation of biological material to construct the vascular and bronchial trees. A fractal design uses a smaller amount of genetic code for pulmonary construction by using a recursive construction mechanism that requires only a handful of proteins.

May 20, 2021 | Posted by in RHEUMATOLOGY | Comments Off on Ventilation/perfusion inequality

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