Ventilation-Perfusion Relationships

September 26, 2016 Cardiology, Mechanical Ventilation, Pulmonary Medicine, Respirology No comments , , , , , , , , , , , , , , ,

Gas exchange between the alveoli and the pulmonary capillary blood occurs by diffusion. Diffusion of oxygen and carbon dioxide occurs passively, according to their concentration differences across the alveolar-capillary barrier. These concentration differences must be maintained by ventilation of the alveoli and persusion of the pulmonary capillaries.

Alveolar ventilation brings oxygen into the lung and removes carbon dioxide fro it. Similarly, the mixed venous blood brings carbon dioxide into the lung and takes up alveolar oxygen. The alveolar PO2 and PCO2 are thus determined by the relationship between alveolar ventilation and pulmonary capillary perfusion. Alterations in the ratio of ventilation to perfusion, called the (VA/QC), will result in changes in the alveolar PO2 and PCO2, as well as in gas delivery to or removal from the lung.

Alveolar ventilation is normally about 4 to 6 L/min and pulmonary blood flow (which is equal to cardiac output) has a similar range, and so the V/Q for the whole lung is in the range of 0.8 to 1.2. However, ventilation and perfusion must be matched on the alveolar-capillary level, and the V/Q for the whole lung is really of interest only as an approximation of the situation in all the alveolar-capillary units of the lung. For instance, suppose that all 5 L/min of the cardiac output went to the left lung and all 5 L/min of alveolar ventilation went to the right lung. The whole lung V/Q would be 1.0, but there would be no gas exchange because there could be no gas diffusion between the ventilated alveoli and the perfused pulmonary capillaries.

Consequences of High and Low V/Q

Oxygen is delivered to the alveolus by alveolar ventilation, is removed from the alveolus as it diffuses into the pulmonary capillary blood, and is carried away by blood flow. Similarly, carbon dioxide is delivered to the alveolus in the mixed venous blood and diffuses into the alveolus in the pulmonary capillary. The carbon dioxide is removed from the alveolus by alveolar ventilation. At resting cardiac outputs the diffusion of both oxygen and carbon dioxide is normally limited by pulmonary perfusion. Thus, the alveolar partial pressures of both oxygen and carbon dioxide are determined by the V/Q. If the V/Q in an alveolar-capillary unit increases, the delivery of oxygen relative to its removal will increase, as will the removal of carbon dioxide relative to its delivery. Alveolar PO2 will therefore rise, and alveolar PCO2 will fall. If the V/Q in an alveolar-capillary unit decreases, the removal of oxygen relative to its delivery will increase and the delivery of carbon dioxide relative to its removal will increase. Alveolar PO2 will therefore fall, and alveolar PCO2 will rise.

Consider these three conditions: 1) A normal V/Q ratio; 2) a V/Q ratio equals to 0; and 3) a V/Q ratio of infinite. With a normal V/Q ratio, inspired air enters the alveolus with a PO2 of about 150 mm Hg and a PCO2 of nearly 0 mm Hg. Mixed venous blood enters the pulmonary capillary with a PO2 of about 40 mm Hg (SvO2 of 75%) and a PCO2 of about 45 mm Hg. This results in an alveolar PO2 of about 100 mm Hg and an alveolar PCO2 of about 45 mm Hg. The partial pressure difference for oxygen diffusion from alveolus to pulmonary capillary is thus about 100 to 40 mm Hg, or 60 mm Hg; the partial pressure gradient for CO2 diffusion from pulmonary capillary to alveolus is only about 45 to 40, or 5 mm Hg.

With a V/Q ratio of 0, the airway supplying has become completely occluded. Its V/Q ratio is zero. As time goes on, the air trapped in the alveolus equilibrates by diffusion with the gas dissolved in the mixed venous blood entering the alveolar-capillary unit (If the occlusion persists, the alveolus is likely to collapse). No gas exchange can occur, and any blood perfusion this alveolus will leave it exactly as it entered it.

With a V/Q ratio of infinite (dead space), the blood flow is blocked by a pulmonary embolus, and the alveolar-capillary unit is therefore completely unperfused. Because no oxygen can diffuse from the alveolus into pulmonary capillary blood and because no carbon dioxide can enter the alveolus is approximately 150 mm Hg and its PCO2 is approximately zero. That is, the gas composition of this unperfused alveolus is the same as that of inspired air. If this condition is due to the fact that the alveolar pressure exceeds its precapillary pressure (pulmonary arterial pressure, Pa), then it would aslo correspond to part of zone 1.

screen-shot-2016-09-21-at-9-11-53-amConditions 2 and 3 represent the 2 extremes of a continuum of ventilation-perfusion ratios. The V/Q ratio of a particular alveolar-capillary unit can fall anywhere along this continuum. The alveolar PO2 and PCO2 of such units will therefore fall between the two extremes shown in the figure: Units wtih low V/Q ratios will have relatively low PO2s and high PCO2s; units with high V/Q ratios will have relatively high PO2s and low PCO2s. This is demonstrated graphically in an O2-CO2 diagram such as that seen in Figure 5-2. The diagram shows the results of mathematical calculations of alveolar PO2s and PCO2s for V/Q ratios between zero and infinity (for inspired air). The resulting curve is known as the ventilation-perfusion ratio line. This simple O2-CO2 diagram can be modified to include correction lines for other factors, such as the respiratory exchange ratios of the alveoli and the blood or the dead space. The position of the V/Q ratio line is altered if the partial pressures of the inspired gas or mixed venous blood are altered.

Evaluation of the Ventilation-Perfusion Mismatch

Physiologic Shunts

Physiologic shunt = Anatomic Shunt + Intrapulmonary shut (absolute + shuntlike)

Anatomic shunts

Anatomic shunts consist of systemic venous blood entering the left ventricle without having entered the pulmonary vasculature. In a normal healthy adult, about 2% to 5% of the cardiac output, including venous blood from the bronchial veins, the besian veins, and the pleural veins, enters the left side of the circulation directly without passing through the pulmonary capillaries. Therefore, the output of the left venticle is normally greater than that of the right venticle in adults.

Absolute intrapulmonary shunts

Mixed venous blood perfusing pulmonary capillaries assocaited with totally unventilation or collapsed alveoli constitutes an absolute shunt (like the anatomic shunts) because no gas exchange occurs as the blood passes through the lung. Absolute shunts are sometimes also referred to as true shunts.

Shuntlike states

Alveolar-capillary units with low V/Q also act to lower the arterial oxygen content because blood draining these units has a lower PO2 than blood from units with well-matched ventilation and perfusion.

The Shunt Equation

The shunt equation conceptually divides all alveolar-capillary units into two groups: those with well-matched ventilation and perfusion and those with ventilation-perfusion ratios of zero. Thus, the shunt equation combines the areas of absolute shunt and the shuntlike areas into a single conceptual group. The resulting ratio of shunt flow to the cardiac output, often referred to as the venous admixture, is the part of the cardiac output that would have to be perfusing absolutely unventilated alveoli to cause the systemic arterial oxygen content obtained from a patient. A much larger portion of the cardiac output could be overperfusion poorly ventilated alveoli and yield the same ratio.

The shunt equation can be derived as follows: Let Qt represent the total pulmonary blood flow per minute (i.e., the cardiac output), and let Qs represent the amount of blood flow per minute entering the systemic arterial blood without receiving any oxygen (the "shunt flow"). The volume of blood per minute that perfuses alveolar-capillary units with well-matched ventilation and perfusion then equals Qt – Qs.

The total volume of oxygen per time entering the systemic arteries is therefore

Qt x CaO2

where CaO2 equals oxygen content of arterial blood in milliliters of oxygen per 100 mL of blood. This total amount of oxygen per 100 mL of blood. This total amount of oxygen per time entering the systemic arteries is composed of the oxygen coming from the well-ventilated and well-perfused alveolar-capillary units:

(Qt – Qs) x CcO2

where CcO2 equals the oxygen content of the blood at the end of the ventilated and perfused pulmonary capillaries, plus the oxygen in the unaltered mixed venous blood coming from the shunt, Qs x CvO2 (where CvO2 is equal to the oxygen content of the mixed venous blood). There is normally a substantial amount of oxygen in the mixed venous blood. That is,

Qt x CaO2 = (Qt – Qs) x CcO2 + Qs x CvO2

After some mathematical rearranagement, the Qs/Qt is expressed as,

Qs/Qt = (CcO2 – CaO2) / (CcO2 – CvO2) [Equation 1]

The shunt fraction Qs/Qt is usually multiplied by 100% so that the shunt flow is expressed as a percentage of the cardiac output.

The arterial and mixed venous oxygen contents can be determined if blood samples are obtained from a systemic artery and from the pulmonary artery (for mixed venous blood), but the oxygen content of the blood at the end of the pulmonary capillaries with well-matched ventialtion and perfusion is, of course, impossible to measure directly. This must be calculated from the alveolar air equation and the patient's hemoglobin concentration.

Physiologic Dead Space

The use of the Bohr equation to determine the physiologic dead space was discussed in detail in thread "Mechanics of Breathing – Alveolar Ventilation" at http://www.tomhsiung.com/wordpress/2015/11/mechanics-of-breathing-alveolar-ventilation/. If the anatomic dead space is subtracted from the physiologic dead space, the result (if there is a difference) is alveolar dead space, or areas of infinite V/Qs. Alveolar dead space also results in an arterial-alveolar CO2 difference; that is, the end-tidal PCO2 is normally equal to the arterial PCO2. End-tidal PCO2 is used as an estimate of the mean PCO2 of all ventilated alveoli. An arterial PCO2 greater than the end-tidal PCO2 usually indicates the presence of alveolar dead space.

Alveolar-Arterial Oxygen Difference

The alveolar and arterial PO2s are treated as though they are equal. However, the aterial PO2 is normally a few mm Hg less than that alveolar PO2. This is normal alveolar-arterial oxygen difference, the (A-a)DO2, is caused by the normal anatomic shunt, some degree of ventilation-perfusion mismatch, and diffusion limitation in some parts of the lung. Of these, V/Q mismatch is usually the most important, with a small contribution from shunts and very little from diffusion limitation. Larger-than-normal differences between the alveolar and arterial PO2 may indicate significant ventilation-perfusion mismatch; however, increased alveolar-arterial oxygen differences also can be caused by anatomic intrapulmonary shunts, diffusion block, low mixed venous PO2s, breathing higher than normal oxygen concentrations, of shifts of the oxy-hemoglobin dissociation curve.

The alveolar-arterial PO2 difference is normally about 5 to 15 mm Hg in a young healthy person breathing room air at sea level. It increases with age because of the progressive decrease in arterial PO2 that occurs with aging. The normal alveolar-arterial PO2 difference increases by about 20 mm Hg between the ages of 20 and 70. A person's age/4 + 4 mm Hg is a good clinical estimate of the normal alveolar-arterial PO2 difference.

Another useful clinical index in addition to the alveolar-arterial oxygen difference is the ratio of arterial PO2 to the fractional concentration of oxygen in the inspired air. The PaO2/FiO2 should be greater than or equal to 200; a PaO2/FiO2 less than 200 is seen in acute respiratory distress syndrome.

Single-Breath Carbon Dioxide Test

The expired concentration of carbon dioxide can be monitored by a rapid-response carbon dioxide meter in a manner similar to that used in the single-breath tests utilizing a nitrogen meter. The alveolar plateau phase of the expired carbon dioxide concentration may show signs of poorly matched ventilation and perfusion if such regions empty asynchronously with other regions of the lung.

Lung Scans After Inhaled and Infused Markers

Lung scans after both inhaled and injected markers can be used to inspect the location and amount of ventilation and perfusion to the various regions of the lung.

Multiple Inert Gas Elimination Technique

A more specific graphic method for assessing ventilation-perfusion relationships in human subjects is called the multiple inert gas elimination technique. This technique uses the concept that the elimination via the lungs of different gases dissolved in the mixed venous blood is affected differently by variations in the ventilation-perfusion ratios of alveolar-capillary units, according to the solubility of each gas in the blood. At a ventilation-perfusion ratio of 1.0, a greater volume of a relatively soluble gas would be the case with a relatively insoluble gas. Thus, the retention of any particular gas by a single alveolar-capillary unit is dependent on the blood-gas partition coefficient of the gas and the ventilation-perfusion ratio of the unit. Gases with very low solubilities in the blood would be retained in the blood only by units with very low (or zero) V/Qs. Gases with very high solubilities in the blood would be eliminated mainly in the expired air of units with very high V/Qs.

Regional V/Q Differences and Their Consequences in the Lung

screen-shot-2016-09-26-at-8-27-08-pmThe regional variations in ventilation in the normal upright lung were discussed in thread "Mechanics of Breathing – Alveolar Ventilation" at http://www.tomhsiung.com/wordpress/2015/11/mechanics-of-breathing-alveolar-ventilation/. Gravity-dependent regions of the lung receive more ventilation per unit volume than do upper regions of the lung when one is breathing near the FRC. The reason for this is that there is a gradient of pleural surface pressure, which is probably caused by gravity and the mechanical interaction of the lung and the chest wall. The pleural surface pressure is more negative in nondependent regions of the lung, and so the alveoli in these areas are subjected to greater transpulmonary pressures. As a result, these alveoli have larger volumes than do alveoli in more dependent regions of the lung and are therefore on a less steep portion of their pressure-volume curves. These less-compliant alveoli change their volume less with each breath than do those in more dependent regions.

The right side of Figure 5-6 shows that the more gravity-dependent regions of the lung also receive more blood flow per unit volume than do the upper regions of the lung, as discussed in thread "Blood flow to the lung – general and pulmonary vascular resistance" at http://www.tomhsiung.com/wordpress/2016/09/blood-flow-to-the-lung-general-and-pulmonary-vascular-resistance/. The reason for this is that the intravascular pressure in the lower regions of the lung is greater because of hydrostatic effects. Blood vessels in more dependent regions of the lung are therefore more distended, or more vessels are perfused because of recruitment so there is less resistance to blood flow in lower regions of the lung.

Regional Differences in the Ventilation-Perfusion Ratios in the Upright Lung

screen-shot-2016-09-26-at-8-39-33-pmSimplified graphs of the differences of ventilation and perfusion from the bottom to the top of normal upright dog lungs are shown plotted on the same axis in Figure 5-7. The ventilation-perfusion ratio was then calculated for several locations.

Figure 5-7 shows that the difference of perfusion from the bottom of the lung to the top is greater than the difference of ventialtion. Because of this, the ventilation-perfusion ratio is relatively low in more gravity-dependent regions of the lung and greater in upper regions of the lung. If pulmonary perfusion pressure is low, for example, because of hemorrhage, or if alveolar pressure is high because of positive-pressure ventilation with positive end-expiratory pressure (PEEP), or if both factors are present, then there may be areas of zone 1 with infinite ventilation-perfusion ratios in the upper parts of the lung.

The Consequences of Regional Ventilation-Perfusion Differences in the Normal Upright Lung

The effects of the regional differences in V/Q on the alveolar PO2 and PCO2 can be seen in Figure 5-8. The lung was arbitrarily divided into 9 imaginary horizontal sections, and the V/Q was calculated for each section. These sections were then positioned on the ventilation-perfusion line of the O2-CO2 diagram, and the PO2 and PCO2 of the alveoli in each section could be estimated. Under normal circumstances the blood in the pulmonary capillaries equilibrates with the alveolar PO2 and PCO2 as it travels through the lung, and so the effects of regional differences in V/Q on the regional gas exchange could be predicted. As can be seen from the figure, the upper sections have relatively high PO2 and low PCO2; the lower sections have relatively low PO2 and high CO2.

Figure 5-7 and 5-8 demonstrate that the lower regions of the lung receive both better ventilation and better perfusion than do the upper portions of the lung. However, the perfusion difference is much steeper than the ventilation difference, and so the ventilation-perfusion ratio is higher in the apical regions than it is in the basal regions. As a result, the alveolar PO2 is greater and the alveolar PCO2 is less in upper portions of the lung than they are in lower regions. This means that the oxugen content of the blood draining the upper regions is greater and the carbon dioxide contnet is less than that of the blood draining the lower regions. However, these contents are based on milliliters of blood, and there is much less blood flow to the upper most sections than there is to the bottom sections. Therefore, even though the uppermost sections have the greatest V/Q and PO2 and the lowest PCO2, there is more gas exchange in the more basal sections.

Effects of Pressure Outside the Heart on Cardiac Output

September 9, 2016 Cardiology, Critical Care, Mechanical Ventilation, Physiology and Pathophysiology, Pulmonary Medicine, Respirology No comments , , , ,

screen-shot-2016-09-09-at-9-37-40-pmIn the figure cited and the preceding dicussions in thread "Pathophysiology of the Circulation" at http://www.tomhsiung.com/wordpress/2016/08/pathophysiology-of-the-circulation/, values of Pms and Pra were expressed relative to atmospheric pressure. However, the transmural pressure of the right atrium exceeds the Pra by the subatmospheric value (about -4 mm Hg) of the Ppl surrounding the heart. Consider the effect of opening the thorax, which raises Ppl from -4 to 0 mm Hg: VR decreases from point A to point B in Figure 31-9 because Pra increases. This is indicated by the interrupted cardiac function curve shifted to the right by the increase in pressure outside the heart but parallel to the normal cardiac function curve (continuous line through point A). Normal VR can be restored (point B to point C) by increasing Pms by an amount equal to the increase in Ppl and Pra induced by thoracotomy. Then transmural Pra will be the same as at point A, and Pra will have increased from point A to point C at the same QT.

This mechanism for the decrease in QT with thoracotomy also partly explains the decrease in QT with PEEP. The Ppl within an intact thorax increases with passive positive-pressure ventilation, thereby increasing Pra and decreasing VR. When 8 mm Hg of PEEP (10 cm H2O) is added to the ventilator, the end-expiratory value of Ppl increases by about half that amount, for example, from -4 to 0 mm Hg. Accordingly, VR decreases with PEEP from point A to pint B in Figure 31-9, with no change in cardiac function or Pms. QT is returned to normal volume infusion or vascular reflexes that increase Pms by an amount equal to the increases in Ppl and Pra. Greater PEEP (20 cm H2O, as in the dotted line shown in Figure 31-8) decreases VR further (from point A to point D) and requires greater increases in Pms to return it to normal (from point D to point E). In one canine study, Pms increases as much as Pra when PEEP is added, so the observed decrease in VR must be due to an increase in RVR with PEEP. In either event, VR can be restored on PEEP by increasing Pms.

QT is much less suceptible to the deleterious effects of PEEP and increased mean intrathoracic pressure when Pms is high. In patients with reduced circulatory volume, vascular reflexes are already operating to maintain VR and Pms by reducing unstressed volume or vascular compliance. Such patients have little vascular reflex reserve and poorly tolerate intubation and positive-pressure ventilation without considerable intravenous infusion to increase vascular stressed volume. In contrast, well-hydrated or overhydrated patients may tolerate even large amounts of PEEP or increased mean intrathoracic pressure from elevated mechanical tidal volumes (VT) with no reduction in QT because their previously inactive vascular reflexes can increase Pms in well-filled systemic vessels by the amount that Ppl increases with PEEP. These considerations allow the physician to anticipate and treat the hypotension induced by ventilator therapy; the concept should not be interpreted as an indication for maintaining high circulatory volume in critical ill patients on ventilators because this often increases lung edema and provides even more QT than was already deemed sufficient. Further, pressure outside the heart can be increased by a variety of other concomitant conditions and complications of critical illness; all these actions increase pressure measured in the heart chambers and decrease heart volume and, as a consequence, are often interpreted as diastolic dysfunction.