Ventilation-Perfusion Relationships PDF

V/Q relationships-1 MOHD 1 November 6th, 2024 Ventilation-Perfusion Relationships Brian K. Gehlbach, MD...

V/Q relationships-1 MOHD 1 November 6th, 2024 Ventilation-Perfusion Relationships Brian K. Gehlbach, MD Department of Internal Medicine/Pulmonary & Critical Care Recommended reading Boron & Boulpaep’s Medical Physiology, Chapter 31 Key terms V/Q ratio West zones Pulmonary vascular recruitment and distension Hypoxic pulmonary vasoconstriction Pulmonary Vascular Resistance (PRV) Pulmonary Capillary Wedge Pressure (PCWP) Shunt I. Overview Imagine a hypothetical scenario in which all of the inspired air is directed to one lung whereas all of the pulmonary blood flow is directed toward the other. Even if the substance of each lung was entirely normal, this arrangement would obviously be lethal. The air and the blood are not exposed to each other! Normal gas exchange requires that ventilation and perfusion be closely matched. In an ideal lung, all of the alveoli behave the same way and exhibit precise matching of ventilation and perfusion. All alveoli are not the same, however, particularly when the lung is affected by disease. In this lecture, we will explore what happens when alveoli are subjected to mismatching of ventilation and perfusion. We will also discuss how the anatomy and regulation of the pulmonary vasculature, and how it serves to preserve normal arterial PO2 via oxygen sensing and hypoxic vasoconstriction. II. The V/Q ratio in a single alveolus determines its PAO2 We’ll begin with a brief review, because the rest of this material requires an understanding of the following fundamental concept. Remember our depiction of the alveolus as a mixing bowl? 1  V/Q relationships-2 THE ALVEOLUS AS MIXING BOWL The alveolus as mixing bowl. Figure PAO2 reflects the from Leff & Schumacker’s Respiratory balance between oxygen influx via Physiology: Basics & Applications. ventilation and oxygen uptake by the pulmonary circulation Maximal PAO2: approaching 150 ____mm Hg 40 mm Hg Minimal PAO2: approaching ____ Hyperventilation Hypoventilation In this model, increasing the amount of ventilation would be analogous to increasing the amount of hot water (inspired gas) that enters the tank, thereby increasing PAO2 and decreasing PACO2. Basically, the greater the ventilation, the more the water in the tank resembles the atmosphere. Conversely, the greater the addition of cold water (mixed venous blood), the more the water in the tank resembles mixed venous blood. The ratio of ventilation to perfusion determines the properties of the mixture in the tank, or alveolus. We also discussed how the alveolar gas equation expresses the determinants of PAO2: PAO2 = FIO2 * (760-47) – PCO2/R where R is the respiratory exchange ratio (VCO2/VO2) representing the ratio of carbon dioxide production to oxygen consumption for the body. This ratio changes under certain conditions, like exercise (to be discussed by Professor Kregel). Most of the time, however, R averages 0.8 at rest, reflecting a VCO2 ≈ 200 ml/minute and VO2≈ 250 ml/minute in a normal-sized adult. Plugging in the numbers (look at the last lecture again), we arrived at a normal PAO2 = 100 mm Hg. Now that we’ve discussed an ideal situation, let’s consider two extremes. Imagine a scenario in which ventilation is increased dramatically out of proportion to perfusion. What is the theoretical upper boundary of PAO2 that we can achieve in this alveolus with this maneuver? It’s 150 mm Hg, the partial pressure of inspired air ([760-47)]*0.21). This would require that the ratio of ventilation to perfusion (the V/Q ratio) be extremely high (essentially infinite). Now imagine a scenario in which ventilation is essentially 0, meaning that no fresh air would reach the mixing bowl. What is the theoretical lower boundary of PAO2 in this circumstance? It’s 40 mm Hg, the pO2 of venous blood. V/Q ratio P A O2 0 40 Normal 100 Infinite 150 In an ideal lung, all alveoli would exhibit V/Q ratios of 1, and because of this, the arterial PaO2 would be the same as the PAO2, or nearly so (e.g. A-a gradient < 10 mm Hg). This is really important! In fact, the latter calculation is frequently used clinically to test the hypothesis that the lung is behaving in an ideal fashion. Of 2  V/Q relationships-3 course, in clinical medicine, it frequently isn’t. Even in health, ventilation and perfusion are not perfectly matched throughout the lung. The reasons for this are that: 1) Pulmonary blood flow is not homogeneous 2) Ventilation is not homogeneous THE IDEAL LUNG 1) Ventilation is homogeneous 2) Pulmonary blood flow (perfusion) is homogeneous 3) All alveoli have V/Q ratios of 1 Is the lung ideal? III. The lungs are not ideal A. Pulmonary blood flow is not homogeneous Because the pulmonary blood vessels are not made of iron but are flexible, the distribution of blood flow is affected by gravity. Transmural pressure (the pressure inside the vessel minus the pressure outside the vessel) increases with gravity from apex to base in an erect individual. Blood vessels dilate in response to this increase in distending pressure. It also turns out that the geometric arrangement of blood vessels contributes to this phenomenon, although this has not made it into many textbooks. As a result, blood flow to the base of the lung is greater than to the apex (see panel on the left below). THE DISTRIBUTION OF BLOOD FLOW IS AFFECTED BY GRAVITY* Blood flow per alveolus according to The base of the region of lung (bottom, middle, or lung is better top) for the upright position. Rhoades perfused than the apex & Bell. Medical Physiology: principles for clinical medicine * and by geometric factors In contrast to the pressures in the pulmonary circulation, the alveolar pressure is essentially the same from top to bottom. When alveolar and vascular pressures are considered together, it is apparent that three zones of pulmonary blood flow exist. These are commonly referred to as West zones, after the physiologist John West, who first described them. In the bottommost zone (zone III), pulmonary capillary pressure > alveolar pressure. The driving gradient for flow is thus the pressure in the pulmonary artery minus the pressure in the pulmonary vein. 3  V/Q relationships-4 In the middle zone (zone II), alveolar pressure lies between pulmonary arterial and pulmonary venous pressures. Capillaries in this zone will flutter between the open and closed states. The driving pressure for pulmonary blood flow in this zone is the difference between the pulmonary arterial and the alveolar pressure. In the topmost zone (zone I), alveolar pressure >intravascular pressures. Capillaries are not perfused in this region. West zones. Pulmonary arteries are depicted on the left side of the figure, while pulmonary veins are shown on the right. From top to bottom are zones I, II, and III. Alveolar pressure is the same in all 3 zones. See text for details. B. Ventilation is not homogeneous Remember from our earlier lecture that the lung has weight, causing the lung to be pulled away from the chest wall at the apex and toward the chest wall at the base. This means that the pleural pressure is not the same at the top of the lung (where it is more negative) as at the bottom of the lung (where it is more positive). Because the pressure in the alveoli is equal to atmosphere pressure and therefore the same everywhere, the transpulmonary pressure (alveolar pressure – pleural pressure) is greater at the apex than at the base. Said another way, different parts of the lung sit at different portions of the pressure-volume curve. As a result, not all alveoli are the same size. VENTILATION IS NOT HOMOGENEOUS The lung has weight Pleural pressure is more negative at the apex than at the base Effects of gravity on the lung. Leff Transpulmonary & Schumacker, Respiratory pressure is greatest at the apex Physiology: Basics & Applications. Not all alveoli are the same size Alveoli at the bases are better ventilated 4  V/Q relationships-5 As a result, the alveoli at the bases are better (more) ventilated than the alveoli at the apices because they are more compliant. Because blood flow is also greater at the base than at the apex, this helps to match ventilation with perfusion and make gas exchange more efficient. This is a good thing! However, there are still imbalances throughout the lung, because the impact of gravity (& the geometric arrangement of the blood vessels) on perfusion is greater than the impact of gravity on ventilation. This means that alveoli at the top of the lung tend to have higher than average V/Q ratios while the reverse is true for alveoli at the bottom of the lung. The impact of this heterogeneity tends to be mitigated by hypoxic pulmonary vasoconstriction (see below), but is not altogether eliminated. NET RESULT Ventilation is greater at the base Blood flow is greater at the base They’re a team!! Still, there are inhomogeneities Apical alveoli have higher avg V/Q ratios than alveoli at bases Effect of inhomogeneities is mitigated somewhat by hypoxic vasoconstriction C. Mismatching of ventilation and perfusion is bad for gas exchange and leads to hypoxemia Imagine now that we expand our concept of the lung from a single alveolus to a 2-alveolus model. 1) Low V/Q units have low PAO2 and therefore the blood leaving them has low PaO2 2) High V/Q units have high PAO2 and therefore the blood leaving them has high PaO2 3) The blood that results from mixing blood from #1 and blood from #2 is not the average of the two PaO2’s, but rather a PaO2 that is closer to the low PaO2 blood. This is because of the sigmoidal shape of the oxyhemoglobin dissociation curve. V/Q MISMATCH: A 2-ALVEOLUS V/Q mismatch. Note that in this example, the MODEL O2 content of mixed arterial blood (at the 1) Low V/Q unit = low PAO2 right of the figure) is not simply the average 2) High V/Q unit = high PAO2 of the two streams of blood, but is actually 3) Mixing #1 and #2 does not = closer in O2 content to the blood leaving the average PAO2 because of shape alveolus with V/Q = 1.2. This is because of oxyhemoglobin hypoxic pulmonary vasoconstriction has dissociation curve 4) Mitigating effects diverted blood flow away from the alveolus of hypoxic vasoconstriction with low PAO2. While we have focused on the effects of V/Q mismatch on oxygenation, V/Q mismatch can also cause problems with CO2 elimination. This occurs when there are high V/Q units, representing areas that are ventilated but not well perfused. At the extreme of this state, when Q=0, the area represents physiologic dead space (e.g. lung that is ventilated but not perfused, as may occur with a pulmonary embolism to this area). The 5  V/Q relationships-6 fall in PACO2 that occurs triggers a compensatory bronchiolar constriction that diverts ventilation away from this area. CONSEQUENCES OF V/Q A PULMONARY PHYSIOLOGIC MISMATCH By ↑ing CO 2 load PEARL on other alveoli 1) Low V/Q units cause hypoxemia 2) High V/Q units cause hypercapnia, especially High V/Q units when Q=0 (physiologic dead space) cannot undo the Generally less of a problem than #1 damage caused Usually overcome by increased ventilation Fall in PACO2 that occurs triggers a by low V/Q compensatory bronchiolar constriction that units! diverts ventilation away from this area IV. Pulmonary hemodynamics A. Overview of the pulmonary circulation DUAL BLOOD SUPPLY TO THE LUNG 20/10 Bronchial circulation 2% of cardiac output Pulmonary circulation 5 liters/min Systemic pressure Supplies non-gas exchanging regions of lung 120/60 Pulmonary circulation Virtually entire cardiac output Systemic circulation 5 liters/min Principal role: expose blood to air Additional functions: delivers substrates, neurohormonal activation, filters blood, serves as reservoir for left heart The lung’s blood supply arises from two distinct circulations: the bronchial circulation and the pulmonary circulation. The bronchial circulation receives approximately 2% of the entire cardiac output and supplies blood to the non-gas exchanging regions of the lung. Bronchial arteries arise from the aorta and thus are under systemic pressure. The pulmonary circulation functions as a high-flow, low-resistance circuit that accommodates the entire cardiac output at a pressure 1/7th that of the systemic circulation. Why the difference between the two circulations? Whereas high systemic pressures are necessary for supplying blood to diverse sites at different flow rates, the pulmonary circulation is not required to adjust its blood flow to suit the needs of a variety of different microcirculations. Low pulmonary artery pressures also ensure that transudation of fluid from the capillary bed into the lung is minimized, thereby preserving gas exchange. The resistance of the pulmonary circulation to blood flow is called Pulmonary Vascular Resistance (PVR). The PVR can be calculated clinically through the use of a pulmonary artery catheter. This long, slender catheter is typically inserted into a large central vein, such as the internal jugular vein. A small balloon on the tip of the catheter is inflated with air and the catheter tip is passed sequentially through the right atrium, right ventricle, and pulmonary artery, its passage guided by pulmonary blood flow like a boat on a stream. Eventually, the tip of the catheter wedges into a small pulmonary artery: 6  V/Q relationships-7 PULMONARY VASCULAR RESISTANCE (PVR) Leff AR, Schumacker PT. Respiratory Physiology: Basics and Applications. Analogy with Ohm’s law again (V=IR) PVR = (MPAP – PCWP)/CO* Multiplication by the constant 80 produces units in dyne x s x cm-5 Leff AR, Schumacker PT. Respiratory Physiology: Basics and Applications. Because the balloon effectively blocks further pulmonary arterial blood flow in the small vessel within which it is lodged, the pressure transducer at the tip of the catheter measures the pressure of the static column of blood that lies between the tip of the catheter and the left atrium. This pressure is called the pulmonary capillary wedge pressure (PCWP), and usually serves as a reasonably accurate approximation of left atrial pressure and, in the absence of mitral valve disease, left ventricular end-diastolic pressure. The PCWP is the outflow pressure of the pulmonary circulation, and therefore can be used to calculate pulmonary vascular resistance, utilizing two additional measurements obtained through this procedure, the inflow pressure (mean pulmonary artery pressure, MPAP) and pulmonary blood flow (cardiac output, CO). By analogy with Ohm’s law: PVR= (MPAP – PCWP)/CO X 80* *Multiplication by the constant 80 produces units in dyne x s x cm-5 Following are normal values for illustration. We will consider what happens during exercise shortly; for now, concentrate on the resting hemodynamics: Hemodynamics of a healthy young man Rest Exercise Pulmonary artery pressure (mm Hg) 20/10 30/11 Mean pulmonary artery pressure (mm Hg) 14 20 Pulmonary capillary wedge pressure (mm Hg) 5 10 Cardiac output (liters/min) 6 16 Pulmonary vascular resistance (dyne x s x cm-5) 120 50 Adapted from Murray JF. Disorders of the Pulmonary Circulation: General principles and diagnostic approach. In: Textbook of Respiratory Medicine. 7  V/Q relationships-8 PULMONARY VASCULAR RESISTANCE (PVR) MPAP = 14 mm Hg PCWP = 5 mm Hg CO = 6 liters/min PVR = (MPAP – PCWP)/CO * 80 PVR = (14-5)/6 * 80 PVR = 120 dyne x s x cm-5 Normal PVR = 80-150 dyne x s x cm-5 at rest Most of the pulmonary vascular resistance resides in the small arterioles and capillaries. The mechanisms regulating pulmonary blood flow are considered below. B. Regulation of pulmonary blood flow is both passive & active Regulation of blood flow in the pulmonary circulation is both passive and active. An example of passive regulation is provided by the response to exercise. During exercise, healthy young individuals may increase their cardiac output up to four-fold. Despite this, pulmonary artery pressure does not increase significantly. For this to be so, PVR must decrease. This occurs through the distension and recruitment (e.g. opening) of small arterioles and capillaries, particularly those in the apices. The volume of blood contained in the lung may double during exercise, reflecting a significant increase in the capacitance of the pulmonary blood vessels. PASSIVE REGULATION OF PVR (AS DURING EXERCISE…) 4 hypothetical blood vessels (2 collapsed, 2 modestly filled) Hicks GH. Cardiopulmonary Distension anatomy and physiology. Recruitment The graphs below show how a small increase in pulmonary arterial pressure is associated with a sizable reduction in PVR and increase in pulmonary blood flow via this mechanism: IN HEALTH, SMALL INCREASES IN PULMONARY ARTERIAL PRESSURE CAUSE LARGE INCREASES IN BLOOD FLOW 8  V/Q relationships-9 Changes in lung volume also affect pulmonary vascular resistance. Pulmonary blood vessels are very compliant. As a result, changes in transmural pressure cause them to be deformed rather easily. Vessels that are surrounded by alveoli—so-called “alveolar vessels”—tend to be crushed when you take a deep breath, as the expanding alveoli compress the vessels coursing between them (see figures below). On the other hand, vessels that are not surrounded by alveoli—“extra-alveolar vessels”—dilate as you take a deep breath, as pleural pressure and the pressure in the interstitial space surrounding these vessels becomes more negative, pulling them open. These effects on pulmonary vascular resistance oppose each other. Total resistance is lowest at functional residual capacity (FRC), or the lung volume present at the end of a normal expiration. LUNG VOLUME ACTIVE REGULATION OF PVR: O2 ALSO AFFECTS PVR Hypoxic pulmonary vasoconstriction -Present in isolated lung tissue Dependence of -Precise mechanism still unclear… vascular resistance -Low pO2 inhibits K+ channels in on lung volume. pulm vasc smooth muscle cells -Depolarization, Ca2+ influx, & Differential effect of contraction inspiration on alveolar and extra-alveolar vessels. -Low pO2: systemic vs pulmonary effects Total resistance -Debate re: evolutionary basis is lowest at FRC Active regulation of PVR, achieved by the active contraction or relaxation of smooth muscle, occurs in response to a number of diverse influences. The most important of these factors is the alveolar oxygen tension. Alveolar hypoxia is a potent pulmonary artery vasoconstrictor. This mechanism of hypoxic pulmonary vasoconstriction has been shown to be present in isolated lung tissue, demonstrating that it requires neither systemic circulating mediators nor an intact nervous system for its expression. The precise mechanism for sensing and effecting this response is still unclear. It appears that hypoxia acts directly on pulmonary vascular smooth muscle cells, probably by inhibiting K+ channels, leading to smooth muscle cell depolarization, Ca2+ influx via voltage-gated Ca2+ channels, and smooth-muscle contraction. This mechanism is critically important for matching ventilation with perfusion, serving to redirect blood flow away from poorly ventilated areas to areas with higher oxygen tensions. Whereas hypoxia causes systemic vessels to dilate, it causes pulmonary vessels to constrict. Unfortunately, this mechanism can also lead to disease. A number of other substances have been identified as important regulators of pulmonary vascular tone. In fact, this resting tone appears to reflect a balance between vasodilating substances like prostacyclin and nitric oxide, and vasoconstrictor substances such as angiotensin II and endothelin-1. Of note, while the pulmonary blood vessels are innervated by the autonomic nervous system it does not appear that neural regulation of pulmonary vascular tone is very important clinically. 9  V/Q relationships-10 Vasoconstrictors Vasodilators Thromboxane Endothelin-1 Nitric oxide Prostaglandins (NO) (PGI2) ETA ETB NO and PGI2 Smooth muscle vasoconstriction Smooth muscle vasodilation proliferation antiproliferation V. Matching V and Q Hypoxic pulmonary vasoconstriction serves as the lung’s major mechanism for routing blood away from diseased lung (e.g. those with low V/Q ratios). In addition, however, some redistribution of ventilation may occur. As mentioned above, in alveoli with high V/Q ratios the PCO2 falls, which leads to the constriction of airway smooth muscle cells and the diversion of ventilation to other V/Q units. The graph below shows the distribution of ventilation and perfusion in a healthy lung. MATCHING V & Q + VI. Hypoxemia due to V/Q mismatch, and the special case of shunt (V/Q=0) Shunt is defined as the passage of blood from the right to the left side of the heart without encountering alveolar gas. Shunts may occur outside the lung, as when there is an atrial septal defect, but we will focus on intrapulmonary shunts. Intrapulmonary shunts are an extreme form of V/Q mismatch, in which V=0. This has many causes, but is often due to diseases that fill the alveoli with water (pulmonary edema), pus (pneumonia), or blood (hemorrhage). Shunts have much more profound effects on oxygenation than “simple” V/Q mismatch, however, which is why they are considered to be a special case. Consider what happens when you administer oxygen to a patient with simple V/Q mismatch. As seen in the example below, raising the fraction of inspired oxygen will overcome the reduction in ventilation to the diseased unit, thereby restoring PAO2 and PaO2. 10  V/Q relationships-11 SIMPLE V/Q MISMATCH: ROOM AIR SIMPLE V/Q MISMATCH: RESPONSIVE TO O2 We don’t average pO2’s! In contrast, PaO2 rises very little when oxygen is administered to a patient with a significant intrapulmonary shunt, let’s say due to pulmonary edema. The blood that leaves areas of the lung flooded with water will have the same PaO2, PaCO2, and CaO2 as when it entered the lung in the first place. Raising the inspired oxygen concentration will not change the fact that these alveoli are not participating in gas exchange! And when blood that leaves these diseased units mixes with blood from parts of the lung with more optimal V/Q ratios, it will severely depress oxygenation. SHUNT (V/Q=0): ROOM AIR SHUNT: LACK OF RESPONSE TO 100% O2 But wait, you say: doesn’t raising the inspired oxygen concentration increase CaO2 in the healthy portions of the lung by increasing the amount of dissolved oxygen (.003 x PaO2)? It does a little—by 2.1 ml/dl in the “ideal compartment” shown above if the patient is given 100% oxygen via an endotracheal tube—but the overall clinical impact of this increase in oxygen delivery is probably small overall in most cases. Thus, shunts are characterized by their lack of response to 100% oxygen. This feature is also used as an aid to diagnosis. Finally, it is worth noting again that while hypoxic vasoconstriction helps to defend PaO2 against V/Q mismatch, including that caused by shunt, it can only help to a degree and may be overcome by competing processes (for instance, vasodilation in the setting of inflammation). 11  V/Q relationships-12 SHUNT WITH & WITHOUT COMPENSATION Hypoxic vasoconstriction serves to match V & Q VII. Mechanisms of hypoxemia MECHANISMS OF HYPOXEMIA 1) Low PIO2 (Mt. Everest) or FIO2 (altitude simulation tent) 2) Diffusion impairment (rarely significant, as we discussed) 3) Hypoventilation (try this with the alveolar gas equation; use a PCO2 of 80) 4) V/Q mismatch (↓ V/Q) 5) Shunt (a special form of V/Q mismatch that we will treat as its own mechanism) *In addition, a low mixed venous SpO2 may exacerbate arterial hypoxemia in the presence of lung disease In addition, a low mixed venous pO2 may exacerbate arterial hypoxemia in the presence of lung disease because the blood that comes back to the lung has a low CaO2 to which the lungs cannot add much. This can be really bad when the patient has a shunt! But a low mixed venous pO2 will not, by itself, cause arterial hypoxemia, although it can be bad for other reasons, as we will discuss when we talk about shock. During this lecture we will move on to Control of Breathing. 12