PULMONARY CIRCULATION General Goal: To describe the role of the pulmonary circulation in gas exchange and to describe in turn the influence of the respiratory system on the pulmonary circulation. Specific Objectives: The student should: 1. be able to list several functions of the lung in addition to gas exchange. 2. be able to give typical values for pressures in the pulmonary artery, pulmonary capillaries and pulmonary veins and know typical pulmonary blood flow values. 3. be able to calculate pulmonary vascular resistance from pressure and flow values, and know resistance is influenced by intravascular pressure, lung volume, and hypoxia. 4. be able to calculate either oxygen consumption or pulmonary blood flow from the Fick Equation given appropriate missing values. 5. know how blood flow distribution changes from apex to base. 6. understand the conditions determining Zone 1, Zone 2 and Zone 3 lung, and know what pressure gradient determines flow in each case. 7. be able to list the three principle causes of right to left shunt, know how shunt affects arterial oxygenation, and how it can be calculated clinically. Resources Lecture: Dr. Baer Reading: West, JB. Respiratory Physiology—The Essentials (4th Ed.) Williams & Wilkins. Chapter 4. Guyton, AC. Medical Physiology (7th Ed.). Chapter 24. Page 38 Respiratory Physiology I. INTRODUCTION A. Anatomy 1. Lung is only organ to receive entire cardiac output. 2. Extra-alveolar vessels vs. alveolar vessels. Pulmonary artery branches run parallel to airways to the level of the terminal bronchioles where they break off to form the capillaries in the alveolar walls. 3. Sheet flow. Pulmonary capillaries are so dense within the alveolar walls that flow can be thought of as capillary lumen interrupted by occasional supporting walls. B. Physiological functions of pulmonary circulation 1. Gas exchange. Add oxygen and remove carbon dioxide from mixed venous blood ( v) . 2. Filter. The pulmonary capillaries trap thrombi and other sources of emboli and prevent them from entering the systemic circulation. 3. Blood reservoir for left ventricle. A portion of the 900 ml of pulmonary blood volume (contained mostly in the veins) can be used to sustain left ventricle output transient during decreases in right heart output. 4. Supply nutrients to lung itself. a) Pulmonary circulation supplies nutrients for the alveolar ducts and alveoli. b) Bronchial vessels from the systemic circulation supply nutrition to the rest of the lung (<3% cardiac output). c) Anatomical shunt. There is usually no separate venous system draining bronchial vessels. Deoxygenated bronchial venous blood mixes with oxygenated pulmonary venous blood in pulmonary veins. 5. Fluid exchange a) Water movement between the alveoli and pulmonary capillaries depends on the difference between hydrostatic forces and oncotic forces. b) Pulmonary capillary hydrostatic pressure is normally 8-10 mmHg. c) Colloid osmotic pressure is normally 28 mmHg. d) Interstitial osmotic pressure is probably 20 mmHg. e) Slight fluid filtration is thought to occur. 6. Angiotensin converting enzyme. Converts angiotensin I to angiotensin II. Pulmonary Circulation Page 39 II. PRESSURES IN THE PULMONARY CIRCULATION A. Pressures in the pulmonary circulation are much lower than pressures in the systemic circulation. Figure 1 B. Normal values 1. Right atrial pressure. Mean value near 0 mmHg. 2. Right ventricle. Systolic = 25 mmHg. Diastolic = 0 mmHg. 3. Pulmonary artery. Mean value about 15 mmHg. Systolic about 25 mmHg. Diastolic about 8 mmHg. 4. Capillary hydrostatic pressure. Mean about 8-10 mmHg. 5. Left atrial pressure. Mean about 5 mmHg. C. Site of major pressure drop 1. Major pressure drop in pulmonary circulation occurs across the capillaries. 2. Major pressure drop in systemic circulation occurs across the arterioles. D. Swan-Ganz catheter is used to measure right sided pressures clinically. 1. Threaded from peripheral vein into vena cava right atrium, right ventricle, pulmonary artery, and finally “wedged” with a balloon in a branch of the pulmonary artery. 2. Can be used to sample mixed venous blood for blood gases, saturations, and pH. 3. Can be used to measure pressures and obtain a wedge pressure. Page 40 Respiratory Physiology E. Pulmonary artery wedge pressure. (Sometimes also called “pulmonary capillary wedge pressure”) 1. Because the catheter blocks flow the pressure looks at the venous end of pulmonary circulation. 2. PAWP estimates left atrial pressure. This can be used to calculate pulmonary vascular resistance and assess left heart function. 3. PAWP is a guide to pulmonary capillary hydrostatic pressure and is used to assess causes of pulmonary edema. III. PULMONARY VASCULAR PVR ( PPA PLA ) / CO A. = (15 mmHg - 5 mmHg) / (6 L / min) = 1.7 mmHg / L / min B. The site of greatest pulmonary vascular resistance is the site of greatest pressure drop, i.e., the pulmonary capillaries. C. Alveolar (capillaries) and extra-alveolar vessels (arteries and veins) have different surrounding pressures. 1. Alveolar vessels are surrounded by alveolar pressure (measured relative to pleural pressure). Transmural pressure is capillary pressure minus alveolar pressure. 2. Extra-alveolar vessels are approximately surrounded by intrapleural pressure. They can be thought of as being tethered to the lung parenchyma. D. Lung inflation tends to expand extra-alveolar and collapse alveolar vessels. 1. Extra-alveolar vessels are expanded by radial traction. 2. Alveolar vessels are collapsed in 2 ways. a) Expansion of extravascular vessels causes capillary hydrostatic pressure and thus capillary transmural pressure to fall. b) Stretching of alveolar walls tends to decrease the radius (increase the resistance) of capillaries. 3. Above FRC, the net effect of alveolar and extra-alveolar changes is that pulmonary vascular resistance increases with lung inflation. Pulmonary Circulation Page 41 Figure 2 The effects of lung volume on pulmonary vascular resistant. PVR is lowest near the FRC and increases at both high and low lung volumes because of the combined effects on the alveolar and extraalveolar vessels. To achieve low lung volumes, one must generate “positive” intrapleural pressures and the extraalveolar vessels are compressed, as seen above in the figure. (Graph after Murray, 1976. Reproduced with permission.) E. Hypoxic vasoconstriction. If alveolar PO2 falls to a region of the lung, the pulmonary arterioles in that region constrict. 1. Vasoconstriction begins when PA O falls below about 70 mmHg. Blood flow 2 will stop almost completely at very low PA O . 2 2. Mechanism is unknown but may involve the release of chemical mediators. It does not involve nerves since it occurs in isolated lungs. 3. Hypoxic vasoconstriction is beneficial in that blood flow goes to ventilated areas where gas exchange can occur. 4. High altitude. Hypoxic vasoconstriction increases right heart works by increasing pulmonary vascular resistance. 5. Transition from fetal to neonatal circulation. First breath increases PA O and 2 is partially responsible for the decreased pulmonary vascular resistance at birth. F. Pulmonary vascular resistance falls as intravascular pressure is increased. Two mechanisms are responsible. 1. Recruitment. Closed vessels or vessels with no flow begin to conduct blood. This is probably the most important mechanism. 2. Distension. Individual capillaries expand. Large radius equates with lower resistance. G. Other substances known to increase pulmonary vascular resistance include serotonin, histamine and norepinephrine. H. Substances known to relax pulmonary vascular smooth muscle include isoproterenol and acetylcholine. Page 42 Respiratory Physiology IV. FICK METHOD OF MEASURING PULMONARY BLOOD FLOW A. Oxygen enters the pulmonary capillary blood by 2 routes. 1. Oxygen consumption ( VO2 ) . This is the oxygen taken up by pulmonary blood per minute across the alveolar walls. 2. Venous blood. Venous blood from the systemic circulation gets pumped into the pulmonary artery and contains some “left-over oxygen”. The amount entering per minute is the product of blood flow (ml/min) and the oxygen content (ml O2/ml venous blood). O2 of venous blood = CvO2 Q B. Oxygen leaves pulmonary capillaries by pulmonary veins. The amount leaving per minute is the product of blood flow (ml/min) and the oxygen content of arterial blood (ml O2/ml arterial blood). O2 of arterial blood = CaO2 Q C. Conservation of mass requires that the amount of O2 entering the capillaries equal the amount of O2 leaving the capillaries in steady state. VO2 (Cv O2 Q) CaO2 Q D. Rearrangement leads to the two commonly used forms of the Fick Equation: VO2 Q(CaO2 CvO2 ) VO2 Q C a O2 C v O2 E. Warning about units. Arterial O2 content C a O and venous O2 content ( C vO ) are 2 2 usually expressed by the laboratory as ml O2/dl blood (i.e., ml O2/100 ml blood). Before carrying out the equations above they should be converted to ml O2/ml blood by dividing them by 100. F. O2 content can be calculated by multiplying fractional O2 saturation by 1.36 [Hb]. Hemoglobin concentration is expressed in g/dl and 1.36 ml O2 can be bound by each g of Hb. V. DISTRIBUTION OF PULMONARY BLOOD FLOW A. Heterogeneity. Not all alveoli receive the same blood flow. The vast majority of this blood flow heterogeneity is not dependent on gravity effects, but exists even between alveoli with similar vertical position, superimposed on this heterogeneity are gravity dependent differences in blood flow. Pulmonary Circulation Page 43 B. Gravitational Effects. Pulmonary blood flow is greatest in dependent portions of the lung. Thus, pulmonary blood flow is greatest at the base (bottom) and least at the apex (top) of the lung in upright individuals. C. Distribution of blood flow can be measured by injecting radioactive xenon intravenously and measuring its distribution with scintillation detectors over the chest. Figure 3 D. Zones of the lung. The lung can be divided into 3 zones depending on the relationship between pulmonary artery pressure (PPA), alveolar pressure (PALV), and pulmonary venous pressure (PPV). 1. Zone 1. PALV > Ppa > PPV. 2. Zone 2. Ppa > PALV > PPV. 3. Zone 3. Ppa > PPV > PALV. E. Due to hydrostatic effects, arterial and venous pressures fall as we move from the bottom to the top of the lung. Since the density of air is small alveolar pressure is the same everywhere. Figure 4 1. Zone 3 conditions exist at the bottom. All blood vessels are fully open. (PPA - PPV) is the pressure gradient driving flow. 2. Zone 2 conditions exist as we move up the lung because PALV > PPV in this region. A state of partial collapse occurs. Flow is driven by the difference between arterial and alveolar pressures (PPA - PALV). Page 44 Respiratory Physiology 3. Zone 1 conditions exist if hydrostatic effects cause both arterial and venous pressures to fall below alveolar pressure. There is no flow because vessels remain completely collapsed. a) Zone 1 conditions are not normally found in man. b) Zone 1 conditions may occur during hemorrhage or during positive pressure ventilation. VI. VENOUS ADMIXTURE (PULMONARY SHUNT) A. Right to left shunt. Said to occur when deoxygenated blood (systemic veins, pulmonary artery) contaminates normally oxygenated blood (pulmonary veins, aorta). 1. Deoxygenated blood draining from the bronchial circulation. 2. Coronary thebesian drainage directly into the left atrium and ventricle. 3. Blood passing through non-ventilated areas of the lung. B. Left to right shunt. Systemic arterial blood (oxygenated) which contaminates pulmonary arterial blood (deoxygenated). C. Two factors determine the effect of right to left shunt. 1. Amount of deoxygenated blood that is added. 2. Saturation and thus the O2 content of the shunted blood. D. Calculating the fraction of blood that is shunted 1. End (pulmonary) capillary PO2 . End-capillary blood is blood before shunt is added. The end capillary PO2 is approximated by alveolar PO2 which in turn comes from alveolar air equation: PA O PI O Pa CO / R 2 2 2 2. End capillary content C c O . Determined from end capillary PO2 and a 2 standard oxygen dissociation curve. 3. Use conservation of mass to determine the fraction of venous admixture (shunt) (QS/QT). The normal value is 6% of pulmonary blood flow. QT x Ca O2 (Qs x CVo (QT Qs ) x CcO2 2 Q s CcO2 Ca O2 Rearranging, this gives Q T CcO2 C vO2 Pulmonary Circulation Page 45 Figure 5 E. Breathing 100% oxygen will not abolish hypoxemia due to shunt because shunted blood is never exposed to the high alveolar PO2 0of ventilated alveoli. PULMONARY CIRCULATION (Study Questions) 1. Name at least 3 important functions of the pulmonary circulation besides gas exchange. 2. Assume a normal value for pulmonary artery pressure a pulmonary capillary wedge pressure of 5 mmHg, and a cardiac output of 5 L/min. What is pulmonary vascular resistance? 3. A patient has a cardiac output of 6 l/min, a pulmonary artery pressure of 30 mmHg, and a pulmonary artery wedge pressure of 20 mmHg. What is the patient’s pulmonary vascular resistance? Is the pulmonary circulation abnormal? What primary type of problem might the patient have? What secondary effects might occur in the lungs? 4. A patient has a cardiac output of 8 L/min, a C a O 2 of 20 ml/dl and a C v O 2 of 14 ml/dl. What is high oxygen consumption ( VO2 ) (include units)? 5. A patient has an oxygen consumption of 500 ml/min. If his arterial-venous oxygen difference is 5 ml/dl, what is his cardiac output (include units)? 6. A portion of lung has a pulmonary artery pressure of 10 mmHg, an alveolar pressure of 5 mmHg and a pulmonary venous pressure of 0 mmHg. Which zone of lung is this? What is the pressure gradient driving flow? What portion of the normal upright lung might be in this condition? 7. Analysis of the alveolar air equation for a patient shows that PA O 2 is 100 mmHg which corresponds on the oxygen dissociation curve to a content of 20 ml/dl. C a O 2 is 19.5 ml/dl and C v O is 13 ml/dl. 2 Right to left shunt represents what percentage of pulmonary blood flow? 8. In which portion of the lung is pulmonary blood flow the greatest when a patient stands on his head? 9. How does pulmonary vascular resistance change if a patient is put on a ventilator with positive end- expiratory pressure (PEEP) to elevate end expiratory lung volume? Under what conditions could this be detrimental? Under what conditions could it be beneficial? 10. True or False. The pulmonary arterioles vasoconstrict in response to an arterial PO2 of below about 70 mmHg. 11. True or False. Diastolic blood pressure is similar in the pulmonary artery and the right ventricle.
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