Pulmonary Circulation Physiology PDF - Feb 2021

Pulmonary circulation physiology Membrane Transport & Membrane Potentials (1) Violetta Raffay, MD, PhD Asst. Professor - School of Medicine EUC Feb 2021 The slides were adapted from Dr Raffay’s slides. Dr Elina Psara...

Pulmonary circulation physiology Membrane Transport & Membrane Potentials (1) Violetta Raffay, MD, PhD Asst. Professor - School of Medicine EUC Feb 2021 The slides were adapted from Dr Raffay’s slides. Dr Elina Psara [email protected]  Learning objectives Understand the bronchial circulation and the pulmonary circulation Describe the anatomy and physiology of the pulmonary circulation Compare and contrast the pulmonary circulation and the systemic circulation Describe and explain the effects of lung volume on pulmonary vascular resistance Describe and explain the effects of elevated intravascular pressures on pulmonary vascular resistance List the neural and humoral factors that influence pulmonary vascular resistance Describe the interrelationships of alveolar pressure, pulmonary arterial pressure, and pulmonary venous pressure, as well as their effects on the regional distribution of pulmonary blood flow Describe hypoxic pulmonary vasoconstriction and discuss its role in localised and widespread alveolar hypoxia  Pulmonary circulation physiology Function of pulmonary system: facilitate gas exchange from environmental air into the circulatory system We breathe in O2, which diffuses into the blood for systemic circulation and ultimately produces ATP for use as energy on a cellular level We breathe out CO2 along with other metabolic byproducts from the body  Pulmonary circulation physiology Each lobe is made up of small sacks of air called alveoli There are approximately 300 million alveoli in healthy lungs It is at the surface of alveoli where diffusion from air into pulmonary arterioles occurs  Diffusion (part 1/4) Diffusion: passive movement from an area of higher concentration into an area of lower concentration Ventilation refers to movement of air into and out of lungs Function of ventilation: to create an environment where O2 is in high concentration in the lung and CO2 is in lower concentration in the lung, relative to pulmonary capillaries Diffusion rate also depends on the solubility of a gas in liquid, gas density, and available surface area for diffusion to occur within the lung  Diffusion (part 2/4) CO2 is highly soluble in physiologic conditions; therefore, O2 is the limiting factor of concern here Total available surface area is a very important variable in pulmonary pathology As total alveolar surface area ↓ relative to available arteriolar perfusion, the available potential space to diffuse O2 into blood ↓. A malformation in any of these parameters may lead to hypoxia  Diffusion (part 3/4) Diffusion limitation exists when movement of O2 from alveoli to pulmonary vasculature is impaired Due to fibrosis of the lung and parenchymal destruction of alveoli leading to a ↓ surface area of alveoli tissue Perfusion: flow of blood through the lungs Ventilation/perfusion ratio (V/Q): measure of the efficiency of gas exchange in the lungs Often diffusion abnormalities are coexistant with V/Q (ventillation/perfusion) mismatching and are most prevalent under exercise conditions  Diffusion (part 4/4) During rest, blood flow through the lung arterioles is slow enough to allow for proper diffusion Under exercise conditions, cardiac output ↑, and there is less time for oxygenation to occur in the lung → transient hypoxia Examples of limited diffusion disease include lung fibrosis and chronic obstructive pulmonary disease (COPD)  Pulmonary circulation The lung receives blood flow via both the bronchial circulation and the pulmonary circulation: Bronchial blood flow: part of systemic circulation that supplies oxygenated blood to the lungs Pulmonary blood flow: carries deoxygenated blood to the lungs for oxygenation and then returns oxygenated blood to the heart  Bronchial circulation The bronchial circulation is important in the “air-conditioning” of inspired air The bronchial arteries arise variably, either directly from the aorta or from the intercostal arteries They supply arterial blood to the tracheobronchial tree and to other structures of the lung down to the level of the terminal bronchioles They also provide blood flow to the hilar lymph nodes, visceral pleura, pulmonary arteries and veins, vagus, and oesophagus  Bronchial circulation Lung structures distal to the terminal bronchioles receive O2 directly by diffusion from the alveolar air and nutrients from the mixed venous blood in the pulmonary circulation The blood flow in the bronchial circulation constitutes about 2% of the output of the left ventricle Blood pressure in the bronchial arteries is the same as that in the other systemic arteries Much higher than the blood pressure in the pulmonary arteries Illustration of the main anatomic features of the bronchial circulation A bronchopulmonary anastomosis is shown at right and is enlarged in the inset Venous drainage is to both the right side of the circulation via the azygos (and hemiazygos) vein and the left side of the circulation via the pulmonary veins Reproduced with permission from Deffebach, Charan, Lakshminarayan, and Butler, 1987  Blood flow to the lung Histologists have identified anastomoses between some bronchial capillaries and pulmonary capillaries and between bronchial arteries and branches of the pulmonary artery These connections probably play little role in a healthy person but may open in pathologic states When either bronchial or pulmonary blood flow to a portion of lung is occluded For example, if pulmonary blood flow to an area of the lung is blocked by a pulmonary embolus, bronchial blood flow to that area ↑)  Pulmonary circulation Pulmonary blood flow undergoes gas exchange with the alveolar air in the pulmonary capillaries Pulmonary blood flow is equal to 100% of the output of the left ventricle Pulmonary blood flow is equal to the cardiac output which is approximately 3.5 L/min/m2 of body surface area at rest 280 billion pulmonary capillaries supply 300 million alveoli One arteriole and an accompanying venule supply and drain one pulmonary lobule Pulmonary circulation: a low-pressure system  Pulmonary circulation division The pulmonary circulation is divided in 3 parts: 1. Arterial circuit 2. Venous circuit 3. Lymphatics  Arterial circuit It arises from the main pulmonary artery arising from the right ventricle It runs a course of only 5 cm before dividing into right and left main branches and many subsequent branches creating a network of small arteries, arterioles, and capillaries These vessels are thinner (1/3 the thickness of their counterpart systemic vessels) and have a larger diameter The combined effect makes them much more distensible and compliant (7 mL/mmHg)  Venous circuit It begins with the venules that drain the capillaries, joining and forming smaller veins and eventually the main pulmonary veins draining into the left atrium Pulmonary veins are also thinner and more distensible than the counterpart systemic veins Pulmonary veins accommodate more blood because of their larger compliance  Lymphatics Lymphatics play a crucial role in maintaining a dry alveolar membrane and preventing accumulation of tissue fluid around the pulmonary circulation They are close to the terminal bronchioles They drain the mediastinal lymphatics before emptying into the right lymphatic duct Pulmonary circulation https://www.britannica.com/science/pulmonary-circulation Schematic representation of gas exchange between the tissues of the body and the environment  Pulmonary circulation physiology There is  250-300 mL of blood/m2 of body surface area in the pulmonary circulation  60-70 mL/m2 of this blood is located in the pulmonary capillaries It takes a RBC  4-5 seconds to travel through the pulmonary circulation at resting cardiac outputs;  0.75 of a second of this time is spent in pulmonary capillaries Pulmonary circulation physiology Scanning electron micrograph of the surface and cross section of an alveolar septum. Capillaries (C) are seen sectioned in the foreground, with erythrocytes (EC) within them. (A) alveolus; (D) alveolar duct; (PK) pore of Kohn; (AR) alveolar entrance to duct; * connective tissue fibers. The encircled asterisk is at a junction of three septa. (Reproduced with permission from Weibel, 1998). Pulmonary circulation physiology Transmission electron micrograph of a cross section of a pulmonary capillary. An erythrocyte (EC) is seen within the capillary. (C) capillary; (EN) capillary endothelial cell (note its large nucleus); (EP) alveolar epithelial cell; (IN) interstitial space; (BM) basement membrane; (FB) fibroblast processes; 2,3,4: diffusion pathway through the alveolar-capillary barrier, the plasma, and the erythrocyte, respectively. (Reproduced with permission from Weibel, 1970).  Blood flow to the lung Pulmonary capillaries have average diameters of around 6 μm They are slightly smaller than the average RBC RBC diameter = 8 μm RBCs must change shape slightly as they pass through the pulmonary capillaries A RBC passes through a number of pulmonary capillaries as it travels through the lung Gas exchange starts to take place in smaller pulmonary arterial vessels, which are not truly capillaries by histologic standards These arterial segments and successive capillaries may be thought of as functional pulmonary capillaries Control of pulmonary vascular smooth muscle Pulmonary vascular smooth muscle is responsive to both neural and humoral influences; these produce “active” alterations in pulmonary vascular resistance (PVR) “Passive” factors (e.g. gravity)  Regulation of pulmonary circulation Pulmonary blood flow is regulated primarily by altering the resistance of the arterioles (PVR) Such changes in resistance are accomplished by changes in the tone of arteriolar smooth muscle In the pulmonary circulation, these changes are mediated by local vasoactive substances, especially O2  Pulmonary vascular resistance R=P1 –P2 ˙Q P1: pressure at the beginning of the tube (in mmHg) P2: pressure at the end of the tube (in mmHg) ˙Q: flow (in mL/min) R: resistance (in mmHg/mL/min)  Regulation of pulmonary circulation Hypoxic vasoconstriction The major factor regulating pulmonary blood flow is the partial pressure of O2 in alveolar gas, PAO2 The mechanism of hypoxic pulmonary vasoconstriction is not completely understood. The response occurs locally, that is, only in the area of the alveolar hypoxia Decreases in PAO2 produce pulmonary vasoconstriction (i.e. hypoxic vasoconstriction)  Regulation of pulmonary circulation Hypoxic vasoconstriction In the lungs, however, hypoxic vasoconstriction occurs as an adaptive mechanism, reducing pulmonary blood flow to poorly ventilated areas where the blood flow would be "wasted" Thus, pulmonary blood flow is directed away from poorly ventilated regions of the lung, where gas exchange would be inadequate, and toward well-ventilated regions of the lung, where gas exchange will be better  Regulation of pulmonary circulation In certain types of lung disease, hypoxic vasoconstriction serves a protective role because, blood can be redirected to alveoli that are well oxygenated without changing overall pulmonary vascular resistance If the lung disease is widespread the compensatory mechanism fails, e.g., severe pneumonia; if there are insufficient areas of well-ventilated alveoli, hypoxemia will occur  Regulation of pulmonary circulation Mechanism of hypoxic vasoconstriction It involves a direct action of alveolar PO2 on the vascular smooth muscle of pulmonary arterioles (recall the proximity of the alveoli to the pulmonary microcirculation) The arterioles and their capillary are very close to the alveoli O2 is quite permeable across cell membranes due to its high lipid solubility When PAO2 is normal (at 100 mmHg), O2 diffuses from the alveoli into the nearby arteriolar smooth muscle cells, causing vaso-relaxation and dilatation to the arterioles If PAO2 is low,