Gas Exchange (Part I) Notes PDF

WSUSOM Medical Physiology – Respiratory Physiology Page | 1 of 8 Pulmonary Blood Flow. GAS EXCHANGE – PART I Learning Objectives 1. Contrast the systemic and pulmonary circulations with respect to pressures, resist...

WSUSOM Medical Physiology – Respiratory Physiology Page | 1 of 8 Pulmonary Blood Flow. GAS EXCHANGE – PART I Learning Objectives 1. Contrast the systemic and pulmonary circulations with respect to pressures, resistance to blood flow, and response to hypoxia. 2. Describe how pulmonary vascular resistance changes with alterations in cardiac output or pulmonary arterial pressure. Explain in terms of distention and recruitment of pulmonary vessels. 3. Describe how pulmonary vascular resistance changes with lung volume. Explain in terms of alterations in alveolar and extra-alveolar blood vessels. 4. Describe the consequence of hypoxic pulmonary vasoconstriction on the distribution of pulmonary blood flow. Lecture Outline I. Pulmonary and bronchial circulation  Pressure in the pulmonary and bronchial blood vessels  Compliance of pulmonary and bronchial blood vessels  Partial pressure of oxygen and carbon dioxide in pulmonary and bronchial blood vessels II. Functions of pulmonary blood flow  Gas exchange  Blood Filter  Blood Reservoir  Metabolism of circulating substances III. Factors that regulate pulmonary blood flow  Hypoxia  Motor Innervation  Vasoactive substances  Recruitment and distension  Hematocrit  Lung volume  Gravity WSUSOM Medical Physiology – Respiratory Physiology Page | 2 of 8 Pulmonary Blood Flow Pulmonary Blood Flow  Once the diaphragm contracts negative pressure is generated and a given volume of air is inspired into the lungs.  At the level of the alveoli, gas exchange occurs in order to replenish depleted oxygen supplies and to rid the body of excess carbon dioxide.  For gas exchange to occur pulmonary blood flow must be in contact with the alveoli for a sufficient period of time to allow equilibration of oxygen and carbon dioxide between the alveoli and pulmonary blood.  All venous return goes through pulmonary circulation (see diagram on left). In comparison to systemic circulation note that the pulmonary artery carries blood that is characterized by a depleted level of oxygen and an elevated level of carbon dioxide (systemic arteries carry blood that have a higher oxygen level and lower levels of carbon dioxide).  The pulmonary veins carry blood that is characterized by elevated oxygen levels and reduced levels of carbon dioxide (systemic veins carry blood that have lower oxygen levels and higher levels of carbon dioxide).  The pulmonary system also differs from systemic circulation in that the blood pressure is lower (see diagram on the right), resistance is lower and compliance is higher. WSUSOM Medical Physiology – Respiratory Physiology Page | 3 of 8 Pulmonary Blood Flow Pulmonary Blood Flow – Bronchial Circulation  The lung has two circulations, the pulmonary circulation that perfuses alveoli and the bronchial circulation that provides nutrients and gas exchange for the conducting airways.  The bronchial circulation is part of the systemic circulation and receives approximately 2 % of the cardiac output from the left heart. Bronchial arteries arise from branches of the aorta, intercostal, subclavian, or internal mammary arteries.  The bronchial arteries supply the tracheobronchial tree with both nutrients and oxygen. Vascular pressures in the bronchial circulation are like those in other systemic vascular beds. About a third of the venous drainage from the bronchial circulation is via the azygos, hemiazygos and intercostal veins which return bronchial venous blood to the right atrium.  About 2/3 of bronchial capillary blood is thought to drain into anastomoses or communicating blood vessels that empty into the pulmonary veins.  This vascular connection between the bronchial and pulmonary circulation is called the bronchopulmonary circulation. This communicating circulation adds a small volume of poorly oxygenated bronchial venous blood to the freshly oxygenated blood in the pulmonary vein. WSUSOM Medical Physiology – Respiratory Physiology Page | 4 of 8 Pulmonary Blood Flow Functions of Pulmonary Blood Flow  In addition to its contribution to pulmonary gas exchange (see section on Gas Exchange), pulmonary circulation is also ideally suited for other functions because of the large blood volume that passes through the lung each minute and the immense capillary surface area available for metabolism.  Functions that are not directly related to gas exchange are referred to as non-respiratory functions. Some non-respiratory functions of the lung vasculature include its role as a blood filter, blood reservoir and metabolizer of circulating substances.  Because pulmonary microvessels are so numerous, some can effectively serve as filters to trap foreign material that are present in blood. If such material is not trapped by pulmonary vessels, they might occlude or impede flow in systemic vessels with a lower tolerance to blood flow interruption.  For example, if fibrin blood clots, gas bubbles, fat cells or other emboli were to enter the arterial side of systemic circulation they could occlude vascular beds with little blood flow reserve. Emboli blocking vessels of the brain or heart could have disastrous consequences such as a stroke or heart attack. However, the pulmonary circulation contains more capillaries than are normally required for gas exchange at rest. Because of this large anatomical and functional reserve, some lung microvessels can be used to trap particles without seriously affecting gas exchange.  Emboli trapped by pulmonary vessels can later be removed by enzymatic processes, macrophage ingestion, or absorption into the lymphatic system. Thus, the blood filter function of the lung microvessels prevents entry of potentially harmful particles into the systemic vessels. Pulmonary circulation can also act as a blood reservoir for the left ventricle. The vessels of pulmonary circulation are very compliant (easily distended) and thus they can typically accommodate about 500 ml of blood in an adult male. This large blood volume can serve as a reservoir for the left ventricle, particularly during periods when left ventricular output momentarily exceeds venous return. Thus, cardiac output can be increased rapidly by drawing on pulmonary blood volume without depending on an instantaneous increase in venous return. Because of this function the lung is sometimes referred to as an accessory heart.  Pulmonary circulation can also act to metabolize circulating substances. Cells that comprise the lung vasculature, particularly endothelial cells that line the vessels lumen, are involved in the uptake or metabolic conversion of several vasoactive substances in the circulation. Lung vascular cells also release biologically active compounds into the circulation that act either locally or in other organs. Some of the substances metabolized by the lung from mixed venous blood are listed in the table to the left. The lung may also synthesize and/or release substances such as histamine, prostaglandins, leukotrienes, platelet activating factor, serotonin and nitric oxide in response to certain conditions such as pulmonary emboli or shock.  WSUSOM Medical Physiology – Respiratory Physiology Page | 5 of 8 Pulmonary Blood Flow Factors that Regulate Pulmonary Blood Flow  Stimuli that evoke contraction or relaxation of vascular smooth muscle actively influence pulmonary vascular resistance, which ultimately impacts pulmonary blood flow.  Alveolar hypoxia has a significant impact on pulmonary vascular resistance. When alveolar partial pressure of oxygen is lower than normal it can elicit constriction of arterial vessels that surround the airway. This phenomenon is known as hypoxic pulmonary vasoconstriction.  The precise factors responsible for hypoxic pulmonary vasoconstriction are not known for certain. However, the vasoconstriction that occurs is thought to redirect blood flow from poorly oxygenated alveoli towards alveoli that have higher levels of oxygen. Thus, hypoxic pulmonary vasoconstriction typically functions to optimize gas exchange.  There are some drawbacks to this response. For example, at high altitude all alveoli are hypoxic. Thus, this could lead to generalized pulmonary vasoconstriction.  The result of this vasoconstriction is an increase in pulmonary arterial pressure and increase in the work of the right heart.  Generalized pulmonary vasoconstriction may be advantageous in some circumstances. For example, during fetal life the general hypoxic environment plays a role in keeping pulmonary vascular resistance high (only approximately 15 % of cardiac output goes through the fetal lung). However, with the first breath the alveoli become oxygenated and resistance falls resulting in an increase in pulmonary blood flow.  In addition to hypoxia, motor innervation of the pulmonary vasculature impact on pulmonary blood flow. The pulmonary veins and arteries of most species are innervated with cholinergic and adrenergic nerve fibers. Although the extent and distribution of motor innervation varies widely between species, cholinergic and adrenergic innervation appears to be more prevalent for pulmonary arteries than for veins. In addition, larger vessels (70-200 μ) appear to be more extensively innervated than smaller vessels.  Various vasoactive substances also impact on pulmonary blood flow. Humoral substances that are in the circulation or are formed by lung endothelial cells are capable or causing pulmonary vascular smooth muscle to contract or relax thereby altering pulmonary vascular resistance and ultimately blood flow. Some of the more common substances are listed in the table.  The importance of all these substances in the regulation of pulmonary vascular resistance is not completely understood. Moreover, these substances may vary depending on pre- existing hypertension or lung injury. WSUSOM Medical Physiology – Respiratory Physiology Page | 6 of 8 Pulmonary Blood Flow Factors that Regulate Pulmonary Blood Flow – Recruitment and Distention  In addition to active factors that regulate pulmonary blood flow there are some passive factors that also influence flow.  Passive changes in pulmonary vascular resistance are common with change in blood flow or left atrial pressure. Whenever blood flow to the lung or left atrial pressure is increased the pulmonary vascular resistance decreases.  Because pulmonary vascular resistance decreases with increases in blood flow, pulmonary arterial pressure is only slightly increased, and the increase is in proportion to the increase in blood flow.  The decreased pulmonary vascular resistance with increases in blood flow or left atrial pressure occurs because of capillary recruitment and distension.  When blood flow or left atrial pressure is increased, previously closed (collapsed) capillaries or capillaries that were open but not perfused are recruited and patent perfused capillaries are further distended as illustrated above.  Thus, increases in systemic arterial pressure or increases in venous return to the right heart could result in recruitment and distention of pulmonary vessels.  Consequently, with more and wider parallel capillaries available for flow the calculated resistance to flow declines because resistances arranged in parallel are added as the reciprocal of the individual resistances.  Since the total cross-sectional area available for flow increases when parallel capillaries are recruited and distended the calculated pulmonary vascular resistance decreases. However, if passively induced increases in pulmonary vasculature pressures are of sufficient magnitude capillary damage and pulmonary edema may develop. WSUSOM Medical Physiology – Respiratory Physiology Page | 7 of 8 Pulmonary Blood Flow Factors that Regulate Pulmonary Blood Flow – Lung Volumes  Lung volume impacts on pulmonary vascular resistance. The alveolar vessels and pulmonary capillaries are exposed to expanding alveoli during inspiration and consequently are compressed. Thus, the diameter and consequently resistance to blood flow offered by these vessels is affected by alveolar pressure.  Alveolar pressure varies continuously during the breathing cycle. When alveolar pressure is increased, it tends to narrow (squeeze) the lung capillary and may increase resistance to flow. Thus, transmural pressure differences in alveolar vessels can also affect the resistance to blood flow, intravascular pressures, and blood flow distribution.  The extra alveolar vessels are exposed to intrapleural pressure and expand as the pressure becomes more negative and as radial traction increases during inspiration.  During quiet breathing intrathoracic pressure is less than atmospheric pressure and becomes increasingly sub-atmospheric with inspiration. Thus, large vessels and airways tend to passively dilate with inspiration as the outside intrathoracic pressure decreases.  Pulmonary vascular resistance is lowest near functional residual capacity and increases at both high and low lung volumes because of the combined effects on the alveolar and extra alveolar vessels. WSUSOM Medical Physiology – Respiratory Physiology Page | 8 of 8 Pulmonary Blood Flow Factors that Regulate Pulmonary Blood flow – Gravity  Blood flow through the pulmonary circulation is impacted by gravity. In an upright individual blood pressure drops 1 cmH2O for each 1 cm increment above the mid-point of the heart.  As shown in the right-hand figure, the pressure in the pulmonary artery decreases from 10 cmH2O at the mid-point of the heart to 0 cmH2O at the apex of the heart. The pressure in the pulmonary artery at the apex of the heart is accompanied by reductions in pressure across the pulmonary capillaries and veins. The result is that the pressure in the alveoli that are surrounded by the pulmonary vessels is greater. This increased alveolar pressure causes the vessels to collapse.  This collapsing pressure is mitigated or eliminated as we move from the apex to the base of the heart. Four distinct zones related to pressure changes in the pulmonary system have been identified:  Zone 1 – PA > Pa > Pv – no blood flow – Not present under normal conditions at rest but may be induced by hemorrhage, positive pressure ventilation or playing a wind instrument.  Zone 2 – Pa > PA > Pv – blood flow is not determined by A-V pressure difference but rather by the arterial- alveolar difference. Arterial pressure increases down Zone 2 while alveolar pressure remains the same, consequently blood flow increases.  Zone 3 – Pa > Pv > PA arterial and venous pressure exceeds alveolar pressure. These pressures increase due to gravity from the top to the bottom of zone 3. Consequently, the passive pulmonary vessels distend resulting in increased radii and reduced resistance.  Zone 4 – Pa > Pv > PA arterial and venous pressure exceeds alveolar pressure. Zone 4 which is at the very base of the lung where blood flow in the extra-alveolar blood vessels is reduced because intrapleural pressure is least negative in this region. Thus, there is less distending pressure across the vessel.