Homeostatic Regulation of the Vascular System

Homeostatic Regulation of the Vascular System Homeostatic Regulation of the Vascular System Bởi: OpenStaxCollege In order to maintain homeostasis in the cardiovascular system and provide adequate blood to the tissues, blood flow must be redirected continually to the tissues as they become more active In a very real sense, the cardiovascular system engages in resource allocation, because there is not enough blood flow to distribute blood equally to all tissues simultaneously For example, when an individual is exercising, more blood will be directed to skeletal muscles, the heart, and the lungs Following a meal, more blood is directed to the digestive system Only the brain receives a more or less constant supply of blood whether you are active, resting, thinking, or engaged in any other activity [link] provides the distribution of systemic blood at rest and during exercise Although most of the data appears logical, the values for the distribution of blood to the integument may seem surprising During exercise, the body distributes more blood to the body surface where it can dissipate the excess heat generated by increased activity into the environment Systemic Blood Flow During Rest, Mild Exercise, and Maximal Exercise in a Healthy Young Individual Organ Mild Maximal Resting exercise exercise (mL/ (mL/ (mL/ min) min) min) Skeletal muscle 1200 4500 12,500 Heart 250 350 750 Brain 750 750 750 Integument 500 1500 1900 Kidney 1100 900 600 Gastrointestinal 1400 1100 600 1/17 Homeostatic Regulation of the Vascular System Systemic Blood Flow During Rest, Mild Exercise, and Maximal Exercise in a Healthy Young Individual Organ Mild Maximal Resting exercise exercise (mL/ (mL/ (mL/ min) min) min) Others (i.e., liver, spleen) 600 400 400 Total 5800 9500 17,500 Three homeostatic mechanisms ensure adequate blood flow, blood pressure, distribution, and ultimately perfusion: neural, endocrine, and autoregulatory mechanisms They are summarized in [link] 2/17 Homeostatic Regulation of the Vascular System Summary of Factors Maintaining Vascular Homeostasis Adequate blood flow, blood pressure, distribution, and perfusion involve autoregulatory, neural, and endocrine mechanisms Neural Regulation The nervous system plays a critical role in the regulation of vascular homeostasis The primary regulatory sites include the cardiovascular centers in the brain that control both 3/17 Homeostatic Regulation of the Vascular System cardiac and vascular functions In addition, more generalized neural responses from the limbic system and the autonomic nervous system are factors The Cardiovascular Centers in the Brain Neurological regulation of blood pressure and flow depends on the cardiovascular centers located in the medulla oblongata This cluster of neurons responds to changes in blood pressure as well as blood concentrations of oxygen, carbon dioxide, and hydrogen ions The cardiovascular center contains three distinct paired components: • The cardioaccelerator centers stimulate cardiac function by regulating heart rate and stroke volume via sympathetic stimulation from the cardiac accelerator nerve • The cardioinhibitor centers slow cardiac function by decreasing heart rate and stroke volume via parasympathetic stimulation from the vagus nerve • The vasomotor centers control vessel tone or contraction of the smooth muscle in the tunica media Changes in diameter affect peripheral resistance, pressure, and flow, which affect cardiac output The majority of these neurons act via the release of the neurotransmitter norepinephrine from sympathetic neurons Although each center functions independently, they are not anatomically distinct There is also a small population of neurons that control vasodilation in the vessels of the brain and skeletal muscles by relaxing the smooth muscle fibers in the vessel tunics Many of these are cholinergic neurons, that is, they release acetylcholine, which in turn stimulates the vessels’ endothelial cells to release nitric oxide (NO), which causes vasodilation Others release norepinephrine that binds to β2 receptors A few neurons release NO directly as a neurotransmitter Recall that mild stimulation of the skeletal muscles maintains muscle tone A similar phenomenon occurs with vascular tone in vessels As noted earlier, arterioles are normally partially constricted: With maximal stimulation, their radius may be reduced to one-half of the resting state Full dilation of most arterioles requires that this sympathetic stimulation be suppressed When it is, an arteriole can expand by as much as 150 percent Such a significant increase can dramatically affect resistance, pressure, and flow Baroreceptor Reflexes Baroreceptors are specialized stretch receptors located within thin areas of blood vessels and heart chambers that respond to the degree of stretch caused by the presence of blood They send impulses to the cardiovascular center to regulate blood pressure Vascular baroreceptors are found primarily in sinuses (small ... Development of the Microfinance system in Russia Anna Kaganova National Business Incubation Association Russian Federation anna_kaganova@mail.ru Small business development in Russia  SMEs have been existing for 12 years;  >5.6 millions (including 4.5 millions of individual entrepreneurs);  90 % of the total number of establishments;  44 % of GDP;  45 % of employment. Sources of financing Commercial banks Regional (State) Funds for Support of Small Entrepreneurship Business partners, relatives or other people Microfinancial Institutes • convinient and especially attractive for entrepreneurs • represent a flexible form of a classical banking credit • permit to set up the business without start-up capital and credit history Basic conditions of Microfinance  IInterest rate is approximately 6-8 % per month in the first borrowing month with its further reduction to 3-4 % per month  TTotal first credit sum fluctuates between $ 500 – 1000 USD  TTerm of payment is till 3 months More advantageous for small size borrowers than classical bank loans Main objective of Microfinance creation of a high dynamic and an effective financial system for SMEs for an additional stimulation of goods and services production and distribution, and also for a mutuality of start-up enterprises in the acquisition of getting profits and a capital accumulation experience Main tasks of Microfinance  to stimulate efficiency access to the financial resources;  to create work places;  to grow of tax proceeds;  to create a credit history for the further development of SMEs through the bank sector;  to barrier SMEs for their transition to the shady sector of economics. Why not a bank? • lack of guarantees; • lack of credit history; • necessity in operating with a small sum of money ($ 500 – 1000 USD); • necessity in quick credit operating (for several days – week); • necessity in other forms of support and consulting; • existent distrust to banks. Microfinancing Programs Position, summary (on Jan, 2003)  Average monthly microloans interest credit rate – 6%  Average loan size – $400 USD  Average volume of credit on one client – $650 USD  Average percentage of a loan repayment – 95%  Loans distribution: • trade – 55%, • rendering of personal services – 24%, • farming – 11%.  63% of all loans are given to beginner entrepreneurs  Demand for Microloans is evaluated on $ 4.5 bln USA Total quantity of MFIs in Russia - approx. 300 MFIs Social Effect of MFIs MFIs create new work places MFIs give an opportunity for economic development for a lot of people in different Russian regions MFIs usually work with economically unprotected entrepreneurs in regions and give them opportunities for economic development More than 70% of program’s clients are women Example: “Credits for Small Enterprises” microfinance program  Credit sum is from $30 till $1000 USD  Term for accepting the decision 1 day  Interest rate is 4 % per month  Guarantee conditions are 2 warranties (husband/wife, business partner or relative) [...]... clients using given them loans  Nowadays: Microfinance activity has become more mature The models of successful operation of MFIs have been worked out, leading to the mature creation MFIs Development Perspectives SMEs meet depositors directly attracting resources from financial institutions reinvestments the National Business Incubator Association of Russia Founded in 1997 by 22 Russian business incubators... Our Projects   APEC Cooperation Center – New Channel for the NBIA of Russia International Networking; The ACC foundation initiated in 2002;  Aims at facilitating Russian businesses’ development through international cooperation and promotion, in the APEC region especially;  Building Cooperative Networks P1: SBT 9780521662161c04 CUNY946/Thomas 978 0 521 66216 1 July 11, 2007 12:28 4 The Critique of the Morality System ROBERT B. LOUDEN Underneath many of Bernard Williams’ sceptical attitudes and arguments in ethics is his flat-out rejection of what he calls “the morality system.” On his view, “we would be better off without it.” 1 But before we can assess this claim, we need to get a better sense of what exactly it is. 1. WHAT IS THE MORALITY SYSTEM? To begin with, it is fundamentally important to keep in mind that for Williams the words ethics and morality are not at all synonymous. Rather, he treats the latter as an unfortunate modern offshoot of the former. As he notes in Chapter 1 of Ethics and the Limits of Philosophy: Iamgoing to suggest that morality should be understood as a particular development of the ethical, one that has a special significance in modern Western culture. It particularly emphasizes certain ethical notions rather than others, developing in particular a special notion of obligation, and it has some peculiar presuppositions. In view of these features it is also, I believe, something we should treat with a special scepticism. 2 We can see already that Williams’ thesis about the morality system is in no small part historical.Hebelieves that human beings’ thinking about how they should live and act has changed drastically between ancient and modern times. 3 At the same time, in so far as he is particularly concerned with the 1 Williams (1985), p. 174. 2 Williams (1985), p. 6. Williams’ distinction between ethics and morality is analogous in several respects to Hegel’s famous contrast between Sittlichkeit (ethical life) and Moralit¨at (abstract morality). In both cases, a more concrete “world-guided” (or, to put it closer to Hegel’s language, a social-role-and-community-guided) conception of ethics is being contrasted to an abstract, universal one, and in both cases the villain defending the latter is Kant. See, e.g., Hegel (1991), §135. 3 Ancient here effectively means pre-Socratic. In Williams (1993), it is argued that “the basic ethical ideas possessed by the Greeks were different from ours, and also in better condition,” p. 4. But the Greeks he has in mind are not the philosophically familiar Plato and Aristotle. 104 P1: SBT 9780521662161c04 CUNY946/Thomas 978 0 521 66216 1 July 11, 2007 12:28 The Critique of the Morality System 105 concepts, presuppositions, and justifications (or lack thereof) employed by people past and present in their thinking on these matters, his position is also plainly philosophical. Needless to say, some readers may disagree with the historical facets of his position, some with the philosophical, and some with both. 4 What are the defining features of the morality system? At the end of Chapter 10 of Ethics and the Limits of Philosophy (in a chapter entitled, “Morality, the Peculiar Institution”), Williams summarizes his discussion as follows: Many philosophical mistakes are woven into morality. It misunderstands obligations, not seeing how they form just one type of ethical considera- tion. It misunderstands practical necessity, thinking it peculiar to the ethical. It misunderstands ethical practical necessity, thinking it peculiar to obliga- tions. Beyond all this, morality makes people think that, without its very special obligation, there is only inclination; without its utter voluntariness, there is only force; without its ultimately pure justice, there is no justice. Its philosophical errors are only the most abstract expressions of a deeply rooted and Presence and regulation of the endocannabinoid system in human dendritic cells Isabel Matias 1 , Pierre Pochard 2 , Pierangelo Orlando 3 , Michel Salzet 4 , Joel Pestel 2 and Vincenzo Di Marzo 1 1 Endocannabinoid Research Group, 1 Istituto di Chimica Biomolecolare, Consiglio Nazionale delle Ricerche, Comprensorio Olivetti, Pozzuoli (Napoli), Italy; 2 Inflammatory Reaction and Allergic diseases Department, INSERM unit, Pasteur Institute, Lille, France; 3 Istituto di Biochimica delle Proteine ed Enzimologia, Consiglio Nazionale delle Ricerche, Comprensorio Olivetti, Pozzuoli (Napoli), Italy; 4 Laboratoire de Neuroimmunite ´ des Anne ´ lides, UMR 8017 CNRS, Universite ´ des Sciences et Technologies de Lille, Villeneuve d’Ascq, France Cannabinoid receptors and their endogenous ligands, the endocannabinoids, have been detected in several blood immune cells, including monocytes/macrophages, basophils and lymphocytes. However, their presence in dendritic cells, which play a key role in the initiation and development of the immune response, has never been in- vestigated. Here we have analyzed human dendritic cells for the presence of the endocannabinoids, anandamide and 2-arachidonoylglycerol (2-AG), the cannabinoid CB 1 and CB 2 receptors, and one of the enzymes mostly responsible for endocannabinoid hydrolysis, the fatty acid amide hydrolase (FAAH). By using a very sensitive liquid chromatography-atmospheric pressure chemical ioniza- tion-mass spectrometric (LC-APCI-MS) method, lipids extracted from immature dendritic cells were shown to contain 2-AG, anandamide and the anti-inflammatory anandamide congener, N-palmitoylethanolamine (PalEtn) (2.1 ± 1.0, 0.14 ± 0.02 and 8.2 ± 3.9 pmolÆ10 )7 cells, respectively). The amounts of 2-AG, but not anandamide or PalEtn, were significantly increased following cell maturation induced by bacterial lipopolysaccharide (LPS) or the allergen Der p 1 (2.8- and 1.9-fold, respectively). By using both RT-PCR and Western immunoblotting, den- dritic cells were also found to express measurable amounts of CB 1 and CB 2 receptors and of FAAH. Cell maturation did not consistently modify the expression of these pro- teins, although in some cell preparations a decrease of the levels of both CB 1 and CB 2 mRNA transcripts was observed after LPS stimulation. These findings demon- strate for the first time that the endogenous cannabinoid system is present in human dendritic cells and can be regulated by cell activation. Keywords: anandamide; 2-arachidonoylglycerol; cannabi- noid; receptor; fatty acid amide hydrolase. The D 9 -tetrahydrocannabinol (THC), the major psychoac- tive component of Cannabis sativa, has been reported to have beneficial effects on the treatment of nausea, glauco- ma, hypertension, migraine, neurological disorders (i.e. epilepsy, Huntington’s disease, Tourette’s syndrome, dys- tonia and Parkinson’s disease) and pain [1], and to play a down-regulatory role on the immune system [2]. Indeed, cannabinoids exhibit immunosuppressive properties and in vitro they weaken humoral immunity [3,4], cell-mediated immunity [5,6] and cellular defenses against infectious agents [7,8]. A modulation of the cytokine network and a decrease of T- and B-cell proliferation have been described in vitro [9]. A reduction of the cytolytic activity of natural killer cells and of antigen presentation was also observed, again in vitro [9]. The endocannabinoid system, comprising membrane receptors Cardiac Physiology Page 1 of 23 MECHANICAL PROPERTIES OF THE HEART AND ITS INTERACTION WITH THE VASCULAR SYSTEM Daniel Burkhoff MD PhD, Associate Professor of Medicine, Columbia University November 11, 2002 Cardiac Physiology Page 2 of 23 MECHANICAL PROPERTIES OF THE HEART AND ITS INTERACTION WITH THE VASCULAR SYSTEM Daniel Burkhoff MD PhD, Associate Professor of Medicine, Columbia University Recommended Reading: Guyton, A. Textbook of Medical Physiology, 10 th Edition. Chapters 9, 14, 20. Berne & Levy. Principles of Physiology. 4 th Edition. Chapter 23. Katz, AM. Physiology of the Heart, 3 rd Edition. Chapter 15. Bers, DM. Cardiac excitation-contraction coupling. Nature 2002;415:198 Learning Objectives: 1. To understand the basic structure of the cardiac muscle cell. 2. To understand how the strength of cardiac contraction is regulated with particular emphasis on understanding the impact of intracellular calcium and sarcomere length (i.e., the basic concepts of excitation–contraction coupling) 3. To understand the basic anatomy of the heart and how whole organ ventricular properties relate to the properties of the muscle cells. 4. To understand the hemodynamic events occurring during the different phases of the cardiac cycle and to be able to explain these on the pressure-volume diagram and on curves of pressure and volume versus time. 5. To understand how the end-diastolic pressure volume relationship (EDPVR) and the end- systolic pressure-volume relationship (ESPVR) characterize ventricular diastolic and systolic properties, respectively. 6. To understand the concepts of contractility, preload, afterload, compliance. 7. To understand what Frank-Starling Curves are and how they are influenced by ventricular afterload and contractility. 8. To understand how afterload resistance can be represented on the PV diagram using the Ea concept and to understand how Ea can be used in concert with the ESPVR to predict how cardiac performance varies with contractility, preload and afterload. Cardiac Physiology Page 3 of 23 I. INTRODUCTION The heart is a muscular pump connected to the systemic and pulmonary vascular systems. Working together, the principle job of the heart and vasculature is to maintain an adequate supply of nutrients in the form of oxygenated blood and metabolic substrates to all of the tissues of the body under a wide range of conditions. The goal of this manuscript is to provide a detailed understanding of the heart as a muscular pump and of the interaction between the heart and the vasculature. The concepts of contractility, preload and afterload are paramount to this understanding and will be the focus and repeating theme throughout the text. A sound understanding of cardiac physiology begins with basic understanding of cardiac anatomy and of the physiology of muscular contraction. These aspects will be reviewed in brief and the interested reader is referred to the supplemental reading material for more detail. Readers already having such knowledge can jump to section IV of ... cavities) within the aorta and carotid 4/17 Homeostatic Regulation of the Vascular System arteries: The aortic sinuses are found in the walls of the ascending aorta just superior to the aortic valve,... both 3/17 Homeostatic Regulation of the Vascular System cardiac and vascular functions In addition, more generalized neural responses from the limbic system and the autonomic nervous system are... mechanisms Neural Regulation The nervous system plays a critical role in the regulation of vascular homeostasis The primary regulatory sites include the cardiovascular centers in the brain that