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Comprehensive Physiology Mar 2016The circulation of the lung is unique both in volume and function. For example, it is the only organ with two circulations: the pulmonary circulation, the main function... (Review)
Review
The circulation of the lung is unique both in volume and function. For example, it is the only organ with two circulations: the pulmonary circulation, the main function of which is gas exchange, and the bronchial circulation, a systemic vascular supply that provides oxygenated blood to the walls of the conducting airways, pulmonary arteries and veins. The pulmonary circulation accommodates the entire cardiac output, maintaining high blood flow at low intravascular arterial pressure. As compared with the systemic circulation, pulmonary arteries have thinner walls with much less vascular smooth muscle and a relative lack of basal tone. Factors controlling pulmonary blood flow include vascular structure, gravity, mechanical effects of breathing, and the influence of neural and humoral factors. Pulmonary vascular tone is also altered by hypoxia, which causes pulmonary vasoconstriction. If the hypoxic stimulus persists for a prolonged period, contraction is accompanied by remodeling of the vasculature, resulting in pulmonary hypertension. In addition, genetic and environmental factors can also confer susceptibility to development of pulmonary hypertension. Under normal conditions, the endothelium forms a tight barrier, actively regulating interstitial fluid homeostasis. Infection and inflammation compromise normal barrier homeostasis, resulting in increased permeability and edema formation. This article focuses on reviewing the basics of the lung circulation (pulmonary and bronchial), normal development and transition at birth and vasoregulation. Mechanisms contributing to pathological conditions in the pulmonary circulation, in particular when barrier function is disrupted and during development of pulmonary hypertension, will also be discussed.
Topics: Animals; Humans; Hypertension, Pulmonary; Lung; Morphogenesis; Pulmonary Circulation; Pulmonary Edema
PubMed: 27065170
DOI: 10.1002/cphy.c140049 -
Chest Jan 2017Hypoxic pulmonary vasoconstriction (HPV) is a homeostatic mechanism that is intrinsic to the pulmonary vasculature. Intrapulmonary arteries constrict in response to... (Review)
Review
Hypoxic pulmonary vasoconstriction (HPV) is a homeostatic mechanism that is intrinsic to the pulmonary vasculature. Intrapulmonary arteries constrict in response to alveolar hypoxia, diverting blood to better-oxygenated lung segments, thereby optimizing ventilation/perfusion matching and systemic oxygen delivery. In response to alveolar hypoxia, a mitochondrial sensor dynamically changes reactive oxygen species and redox couples in pulmonary artery smooth muscle cells (PASMC). This inhibits potassium channels, depolarizes PASMC, activates voltage-gated calcium channels, and increases cytosolic calcium, causing vasoconstriction. Sustained hypoxia activates rho kinase, reinforcing vasoconstriction, and hypoxia-inducible factor (HIF)-1α, leading to adverse pulmonary vascular remodeling and pulmonary hypertension (PH). In the nonventilated fetal lung, HPV diverts blood to the systemic vasculature. After birth, HPV commonly occurs as a localized homeostatic response to focal pneumonia or atelectasis, which optimizes systemic Po without altering pulmonary artery pressure (PAP). In single-lung anesthesia, HPV reduces blood flow to the nonventilated lung, thereby facilitating thoracic surgery. At altitude, global hypoxia causes diffuse HPV, increases PAP, and initiates PH. Exaggerated or heterogeneous HPV contributes to high-altitude pulmonary edema. Conversely, impaired HPV, whether due to disease (eg, COPD, sepsis) or vasodilator drugs, promotes systemic hypoxemia. Genetic and epigenetic abnormalities of this oxygen-sensing pathway can trigger normoxic activation of HIF-1α and can promote abnormal metabolism and cell proliferation. The resulting pseudohypoxic state underlies the Warburg metabolic shift and contributes to the neoplasia-like phenotype of PH. HPV and oxygen sensing are important in human health and disease.
Topics: Humans; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Oxygen Consumption; Pulmonary Circulation; Pulmonary Gas Exchange; Vasoconstriction
PubMed: 27645688
DOI: 10.1016/j.chest.2016.09.001 -
European Journal of Heart Failure Mar 2016Acute right ventricular (RV) failure is a complex clinical syndrome that results from many causes. Research efforts have disproportionately focused on the failing left... (Review)
Review
Contemporary management of acute right ventricular failure: a statement from the Heart Failure Association and the Working Group on Pulmonary Circulation and Right Ventricular Function of the European Society of Cardiology.
Acute right ventricular (RV) failure is a complex clinical syndrome that results from many causes. Research efforts have disproportionately focused on the failing left ventricle, but recently the need has been recognized to achieve a more comprehensive understanding of RV anatomy, physiology, and pathophysiology, and of management approaches. Right ventricular mechanics and function are altered in the setting of either pressure overload or volume overload. Failure may also result from a primary reduction of myocardial contractility owing to ischaemia, cardiomyopathy, or arrhythmia. Dysfunction leads to impaired RV filling and increased right atrial pressures. As dysfunction progresses to overt RV failure, the RV chamber becomes more spherical and tricuspid regurgitation is aggravated, a cascade leading to increasing venous congestion. Ventricular interdependence results in impaired left ventricular filling, a decrease in left ventricular stroke volume, and ultimately low cardiac output and cardiogenic shock. Identification and treatment of the underlying cause of RV failure, such as acute pulmonary embolism, acute respiratory distress syndrome, acute decompensation of chronic pulmonary hypertension, RV infarction, or arrhythmia, is the primary management strategy. Judicious fluid management, use of inotropes and vasopressors, assist devices, and a strategy focusing on RV protection for mechanical ventilation if required all play a role in the clinical care of these patients. Future research should aim to address the remaining areas of uncertainty which result from the complexity of RV haemodynamics and lack of conclusive evidence regarding RV-specific treatment approaches.
Topics: Echocardiography; Heart Failure; Humans; Pulmonary Circulation; Ventricular Dysfunction, Right
PubMed: 26995592
DOI: 10.1002/ejhf.478 -
Clinics in Perinatology Sep 2016The physiology of the fetus is fundamentally different from the neonate, with both structural and functional distinctions. The fetus is well-adapted to the relatively... (Review)
Review
The physiology of the fetus is fundamentally different from the neonate, with both structural and functional distinctions. The fetus is well-adapted to the relatively hypoxemic intrauterine environment. The transition from intrauterine to extrauterine life requires rapid, complex, and well-orchestrated steps to ensure neonatal survival. This article explains the intrauterine physiology that allows the fetus to survive and then reviews the physiologic changes that occur during the transition to extrauterine life. Asphyxia fundamentally alters the physiology of transition and necessitates a thoughtful approach in the management of affected neonates.
Topics: Adaptation, Physiological; Ductus Arteriosus; Female; Fetus; Foramen Ovale; Heart; Humans; Infant, Newborn; Lung; Parturition; Pregnancy; Pulmonary Circulation
PubMed: 27524443
DOI: 10.1016/j.clp.2016.04.001 -
European Heart Journal Mar 2016In patients with left ventricular heart failure (HF), the development of pulmonary hypertension (PH) and right ventricular (RV) dysfunction are frequent and have... (Review)
Review
In patients with left ventricular heart failure (HF), the development of pulmonary hypertension (PH) and right ventricular (RV) dysfunction are frequent and have important impact on disease progression, morbidity, and mortality, and therefore warrant clinical attention. Pulmonary hypertension related to left heart disease (LHD) by far represents the most common form of PH, accounting for 65-80% of cases. The proper distinction between pulmonary arterial hypertension and PH-LHD may be challenging, yet it has direct therapeutic consequences. Despite recent advances in the pathophysiological understanding and clinical assessment, and adjustments in the haemodynamic definitions and classification of PH-LHD, the haemodynamic interrelations in combined post- and pre-capillary PH are complex, definitions and prognostic significance of haemodynamic variables characterizing the degree of pre-capillary PH in LHD remain suboptimal, and there are currently no evidence-based recommendations for the management of PH-LHD. Here, we highlight the prevalence and significance of PH and RV dysfunction in patients with both HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF), and provide insights into the complex pathophysiology of cardiopulmonary interaction in LHD, which may lead to the evolution from a 'left ventricular phenotype' to a 'right ventricular phenotype' across the natural history of HF. Furthermore, we propose to better define the individual phenotype of PH by integrating the clinical context, non-invasive assessment, and invasive haemodynamic variables in a structured diagnostic work-up. Finally, we challenge current definitions and diagnostic short falls, and discuss gaps in evidence, therapeutic options and the necessity for future developments in this context.
Topics: Heart Failure; Hemodynamics; Humans; Hypertension, Pulmonary; Mitral Valve Insufficiency; Phenotype; Pulmonary Circulation; Ventricular Dysfunction, Left
PubMed: 26508169
DOI: 10.1093/eurheartj/ehv512 -
Critical Care (London, England) Sep 2016The primary role of the right ventricle (RV) is to deliver all the blood it receives per beat into the pulmonary circulation without causing right atrial pressure to... (Review)
Review
The primary role of the right ventricle (RV) is to deliver all the blood it receives per beat into the pulmonary circulation without causing right atrial pressure to rise. To the extent that it also does not impede left ventricular (LV) filling, cardiac output responsiveness to increased metabolic demand is optimized. Since cardiac output is a function of metabolic demand of the body, during stress and exercise states the flow to the RV can vary widely. Also, instantaneous venous return varies widely for a constant cardiac output as ventilatory efforts alter the dynamic pressure gradient for venous return. Normally, blood flow varies with minimal changes in pulmonary arterial pressure. Similarly, RV filling normally occurs with minimal increases in right atrial pressure. When pulmonary vascular reserve is compromised RV ejection may also be compromised, increasing right atrial pressure and limiting maximal cardiac output. Acute increases in RV outflow resistance, as may occur with acute pulmonary embolism, will cause acute RV dilation and, by ventricular interdependence, markedly decreased LV diastolic compliance, rapidly spiraling to acute cardiogenic shock and death. Treatments include reversing the causes of pulmonary hypertension and sustaining mean arterial pressure higher than pulmonary artery pressure to maximal RV coronary blood flow. Chronic pulmonary hypertension induces progressive RV hypertrophy to match RV contractility to the increased pulmonary arterial elastance. Once fully developed, RV hypertrophy is associated with a sustained increase in right atrial pressure, impaired LV filling, and decreased exercise tolerance. Treatment focuses on pharmacologic therapies to selectively reduce pulmonary vasomotor tone and diuretics to minimize excessive RV dilation. Owning to the irreversible nature of most forms of pulmonary hypertension, when the pulmonary arterial elastance greatly exceeds the adaptive increase in RV systolic elastance, due to RV dilation, progressive pulmonary vascular obliteration, or both, end stage cor pulmonale ensues. If associated with cardiogenic shock, it can effectively be treated only by artificial ventricular support or lung transplantation. Knowing how the RV adapts to these stresses, its sign posts, and treatment options will greatly improve the bedside clinician's ability to diagnose and treat RV dysfunction.
Topics: Cardiac Output; Heart Ventricles; Humans; Hypertension, Pulmonary; Pulmonary Circulation; Ventricular Dysfunction, Right
PubMed: 27613549
DOI: 10.1186/s13054-016-1440-0 -
Journal of the American College of... Jan 2017In pulmonary hypertension, the right ventricle adapts to the increasing vascular load by enhancing contractility ("coupling") to maintain flow. Ventriculoarterial... (Review)
Review
In pulmonary hypertension, the right ventricle adapts to the increasing vascular load by enhancing contractility ("coupling") to maintain flow. Ventriculoarterial coupling implies that stroke volume changes little while preserving ventricular efficiency. Ultimately, a phase develops where ventricular dilation occurs in an attempt to limit the reduction in stroke volume, with uncoupling and increased wall stress as a consequence. With pressure-volume analysis, we separately describe the changing properties of the pulmonary vascular system and the right ventricle, as well as their coupling, as important concepts for understanding the changes that occur in pulmonary hypertension. On the basis of the unique properties of the pulmonary circulation, we show how all relevant physiological parameters can be derived using an integrative approach. Because coupling is maintained by hypertrophy until the end stage of the disease, when progressive dilation begins, right ventricular volume is the essential parameter to measure in follow-up of patients with pulmonary hypertension.
Topics: Cardiac Volume; Follow-Up Studies; Heart Ventricles; Humans; Hypertension, Pulmonary; Hypertrophy, Right Ventricular; Magnetic Resonance Imaging; Myocardial Contraction; Pulmonary Artery; Pulmonary Circulation; Risk Factors; Stroke Volume
PubMed: 28081831
DOI: 10.1016/j.jacc.2016.10.047 -
Comprehensive Physiology Jun 2019The pulmonary circulation carries deoxygenated blood from the systemic veins through the pulmonary arteries to be oxygenated in the capillaries that line the walls of... (Review)
Review
The pulmonary circulation carries deoxygenated blood from the systemic veins through the pulmonary arteries to be oxygenated in the capillaries that line the walls of the pulmonary alveoli. The pulmonary circulation carries the cardiac output with a relatively low driving pressure, and so differs considerably in structure and function from the systemic circulation to maintain a low-resistance vascular system. The pulmonary circulation is often considered to be a quasi-static system in both experimental and computational studies of pulmonary perfusion and its matching to ventilation (air flow) for exchange. However, the system is highly dynamic, with cardiac output and regional perfusion changing with posture, exercise, and over time. Here we review this dynamic system, with a focus on understanding the physiology of pulmonary vascular dynamics across spatial and temporal scales, and the changes to these dynamics that are reflective of disease. © 2019 American Physiological Society. Compr Physiol 9:1081-1100, 2019.
Topics: Animals; Cardiac Output; Gravitation; Humans; Hypertension, Pulmonary; Microcirculation; Pulmonary Artery; Pulmonary Circulation; Pulmonary Gas Exchange; Pulmonary Veins; Vasoconstriction
PubMed: 31187894
DOI: 10.1002/cphy.c180033 -
Seminars in Respiratory and Critical... Oct 2023The pulmonary circulation is a low-pressure, low-resistance circuit whose primary function is to deliver deoxygenated blood to, and oxygenated blood from, the pulmonary... (Review)
Review
The pulmonary circulation is a low-pressure, low-resistance circuit whose primary function is to deliver deoxygenated blood to, and oxygenated blood from, the pulmonary capillary bed enabling gas exchange. The distribution of pulmonary blood flow is regulated by several factors including effects of vascular branching structure, large-scale forces related to gravity, and finer scale factors related to local control. Hypoxic pulmonary vasoconstriction is one such important regulatory mechanism. In the face of local hypoxia, vascular smooth muscle constriction of precapillary arterioles increases local resistance by up to 250%. This has the effect of diverting blood toward better oxygenated regions of the lung and optimizing ventilation-perfusion matching. However, in the face of global hypoxia, the net effect is an increase in pulmonary arterial pressure and vascular resistance. Pulmonary vascular resistance describes the flow-resistive properties of the pulmonary circulation and arises from both precapillary and postcapillary resistances. The pulmonary circulation is also distensible in response to an increase in transmural pressure and this distention, in addition to recruitment, moderates pulmonary arterial pressure and vascular resistance. This article reviews the physiology of the pulmonary vasculature and briefly discusses how this physiology is altered by common circumstances.
Topics: Humans; Vasoconstriction; Vascular Resistance; Lung; Pulmonary Circulation; Hypoxia; Blood Pressure
PubMed: 37816344
DOI: 10.1055/s-0043-1770059 -
Current Topics in Membranes 2018
Topics: Cell Membrane; Endothelium, Vascular; Humans; Lung; Pulmonary Circulation; Vascular Diseases
PubMed: 30360785
DOI: 10.1016/S1063-5823(18)30049-8