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The Hepatic circulation is unique among vascular beds. The most obvious unique features include the dual vascular supply; the mechanism of intrinsic regulation of the hepatic artery (the hepatic arterial buffer response); the fact that portal blood flow, supplying two thirds of liver blood flow, is not controlled directly by the liver; the fact that 20% of the cardiac output rushes through the most vascularized organ in the body, driven by a pressure gradient of only a few millimeters of mercury; the extremely distensible capacitance and venous resistance sites; the unidirectional acinar blood flow that regulates parenchymal cell metabolic specialization; and the high concentration of macrophagic (Kupffer) cells filtering the blood. The liver is the only organ reported to have regional blood flow monitored by the autonomic nervous system. This mechanism, when dysfunctional, accounts for the hepatorenal syndrome and offers a mechanistic therapeutic target to treat this syndrome. The trigger for liver regeneration is dependent on hepatic hemodynamics so that chronic liver blood flow regulates liver cell mass. In severe liver disease, the whole body circulation is reorganized, by forming portacaval shunts, to accommodate the increased intrahepatic venous resistance. These shunts protect the venous drainage of the splanchnic organs but lead to loss of major regulatory roles of the liver. The development of knowledge of the hepatic vasculature is presented from a historical perspective with modern concepts summarized based on the perspective of the author's four decades of devotion to this most marvelous of organs. Table of Contents: Acknowledgements / Historical Perspectives / Overview / Fluid Exchange / Capacitance / Resistance in the Hepatic Artery / Resistance in the Venous System / Fetal and Neonatal Hepatic Circulation / In Vivo Pharmacodynamic Approaches / Nitric Oxide / Adenosine / Hepatic Nerves / Hepatic Circulation and Toxicology / Hepatorenal Syndrome / Integrative Hepatic Response to Hemorrhage / Blood Flow Regulation of Hepatocyte Proliferation / Multiple Mechanisms Maintaining a Constant Hepatic Blood Flow to Liver Mass Ratio / Pathopharmacology and Repurposing Drugs as a Research Strategy / References
The microcirculation of the gastrointestinal tract is under the control of both myogenic and metabolic regulatory systems. The myogenic mechanism contributes to basal vascular tone and the regulation of transmural pressure, while the metabolic mechanism is responsible for maintaining an appropriate balance between O2 demand and O2 delivery. In the postprandial state, hydrolytic products of food digestion elicit a hyperemia, which serves to meet the increased O2 demand of nutrient assimilation. Metabolically linked factors (e.g., tissue pO2, adenosine) are primarily responsible for this functional hyperemia. The fenestrated capillaries of the gastrointestinal mucosa are relatively permeable to small hydrolytic products of food digestion (e.g., glucose), yet restrict the transcapillary movement of larger molecules (e.g., albumin). This allows for the absorption of hydrolytic products of food digestion without compromising the oncotic pressure gradient governing transcapillary fluid movement and edema formation. The gastrointestinal microcirculation is also an important component of the mucosal defense system whose function is to prevent (and rapidly repair) inadvertent epithelial injury by potentially noxious constituents of chyme. Two pathological conditions in which the gastrointestinal circulation plays an important role are ischemia/reperfusion and chronic portal hypertension. Ischemia/reperfusion results in mucosal edema and disruption of the epithelium due, in part, to an inflammatory response (e.g., increase in capillary permeability to macromolecules and neutrophil infiltration). Chronic portal hypertension results in an increase in gastrointestinal blood flow due to an imbalance in vasodilator and vasoconstrictor influences on the microcirculation. Table of Contents: Introduction / Anatomy / Regulation of Vascular Tone and Oxygenation / Extrinsic Vasoregulation: Neural and Humoral / Postprandial Hyperemia / Transcapillary Solute Exchange / Transcapillary Fluid Exchange / Interaction of Capillary and Interstitial Forces / Gastrointestinal Circulation and Mucosal Defense / Gastrointestinal Circulation and Mucosal Pathology I: Ischemia/Reperfusion / Gastrointestinal Circulation and Mucosal Pathology II: Chronic Portal Hypertension / Summary and Conclusions / References / Author Biography
This presentation describes various aspects of the regulation of tissue oxygenation, including the roles of the circulatory system, respiratory system, and blood, the carrier of oxygen within these components of the cardiorespiratory system. The respiratory system takes oxygen from the atmosphere and transports it by diffusion from the air in the alveoli to the blood flowing through the pulmonary capillaries. The cardiovascular system then moves the oxygenated blood from the heart to the microcirculation of the various organs by convection, where oxygen is released from hemoglobin in the red blood cells and moves to the parenchymal cells of each tissue by diffusion. Oxygen that has diffused into cells is then utilized in the mitochondria to produce adenosine triphosphate (ATP), the energy currency of all cells. The mitochondria are able to produce ATP until the oxygen tension or PO2 on the cell surface falls to a critical level of about 4–5 mm Hg. Thus, in order to meet the energetic needs of cells, it is important to maintain a continuous supply of oxygen to the mitochondria at or above the critical PO2 . In order to accomplish this desired outcome, the cardiorespiratory system, including the blood, must be capable of regulation to ensure survival of all tissues under a wide range of circumstances. The purpose of this presentation is to provide basic information about the operation and regulation of the cardiovascular and respiratory systems, as well as the properties of the blood and parenchymal cells, so that a fundamental understanding of the regulation of tissue oxygenation is achieved.
​Vascular management and care has become a truly multidisciplinary enterprise as the number of specialists involved in the treatment of patients with vascular diseases has steadily increased. While in the past, treatments were delivered by individual specialists, in the twenty-first century a team approach is without doubt the most effective strategy. In order to promote professional excellence in this dynamic and rapidly evolving field, a shared knowledge base and interdisciplinary standards need to be established. Pan Vascular Medicine, 2nd edition has been designed to offer such an interdisciplinary platform, providing vascular specialists with state-of-the art descriptive and procedural knowledge. Basic science, diagnostics, and therapy are all comprehensively covered. In a series of succinct, clearly written chapters, renowned specialists introduce and comment on the current international guidelines and present up-to-date reviews of all aspects of vascular care.
Chronic liver failure is a frequent condition in clinical practice that encompasses all manifestations of patients with end-stage liver diseases. Chronic liver failure is a multiorgan syndrome that affects the liver, kidneys, brain, heart, lungs, adrenal glands, and vascular, coagulation, and immune systems. Chronic Liver Failure: Mechanisms and Management covers for the first time all aspects of chronic liver failure in a single book, from pathogenesis to current management. Each chapter is written by a worldwide known expert in their area and all provide the latest state-of-the-art knowledge. This volume is specifically designed to provide answers to clinical questions to all doctors dealing with patients with liver diseases, not only clinical gastroenterologists and hepatologists, but also to internists, nephrologists, intensive care physicians, and transplant surgeons.
Liver Pathophysiology: Therapies and Antioxidants is a complete volume on morphology, physiology, biochemistry, molecular biology and treatment of liver diseases. It uses an integral approach towards the role of free radicals in the pathogenesis of hepatic injury, and how their deleterious effects may be abrogated by the use of antioxidants. Written by the most prominent authors in the field, this book will be of use to basic and clinical scientists and clinicians working in the biological sciences, especially those dedicated to the study and treatment of liver pathologies. - Presents the most recent advances in hepatology, with a special focus on the role of oxidative stress in liver injury. - Provides in vivo and in vitro models to study human liver pathology. - Explains the beneficial effects of antioxidants on liver diseases. - Contains the most recent and modern treatments of hepatic pathologies, including, but not limited to, stem cells repopulation, gene therapy and liver transplantation.
A new, fully updated edition of the world’s most famous book on liver diseases—with updating of all areas and inclusion of new specific topics, by internationally renowned specialists This brand new edition of the classic book on hepatology provides a concise, clearly presented and well-structured review across the whole spectrum of hepatobiliary diseases by some of the world’s leading hepatologists and hepatobiliary specialists. Where many other hepatology textbooks provide detailed accounts of basic science and clinical management, Sherlock's Diseases of the Liver and Biliary System, 13th Edition takes a different approach. Concentrating on the clinical decisions to be taken and the relevant supporting data, it is written and edited to maintain Sheila Sherlock's unique approach, in particular the clarity and layout of the text, and the explanatory figures and tables. The book is thus concise, highly accessible, and generously illustrated with over 700 attractive color figures. There is a pithy approach to each disease based both on evidence and on the authors’ experience, the hallmark of this book. Based on these elements, the 12th edition was awarded first prize in the 2012 British Medical Association Book Awards in the Internal Medicine category. Sherlock's Diseases of the Liver and Biliary System begins by introducing the anatomy and function of the liver to readers, continuing then with in-depth coverage of liver biopsy techniques and interpretation, and fibrogenesis and its assessment. There are then chapters on all aspects of liver and biliary disease including acute liver failure, cirrhosis, portal hypertension, hepatic encephalopathy, ascites, hepatitis B and C, alcohol and the liver, non-alcoholic fatty liver disease, drug related liver reactions, cholestatic, autoimmune and genetic liver diseases, benign and malignant tumours and not least liver transplantation. There are also chapters on the liver in pregnancy, in the neonate, infancy and childhood, in systemic diseases and in infections. This new edition also features four new individual chapters focusing on coagulation, non-invasive assessment of fibrosis and cirrhosis; vascular diseases of the liver and portal vein thrombosis, and nutrition in liver disease. Digital downloads of the figures from this edition are offered on a companion website. Internationally recognized and loved, world-renowned hepatology book, first published in 1955 Takes a one-of-a-kind, clinical approach maintaining Sheila Sherlock’s clarity and legacy of presentation Full colour throughout with 700 illustrative figures Wide faculty of international contributors Sherlock's Diseases of the Liver and Biliary System, 13th Edition is an ideal primer in hepatology for students and trainees in hepatology and gastroenterology, and a valuable resource for all specialist gastroenterologists and hepatologists, paediatricians, pathologists, radiologists, general physicians and specialist nurses.
Easily understood, up-to-date and clinically relevant, this book provides junior anaesthetists with an essential physiology resource.
Part 3 of the Handbook of Experimental Pharmacology (Concepts in Biochem ical Pharmacology) applies the principles enunciated in Parts 1 and 2 to clinical pharmacology and toxicology. The major objective is to elucidate the many factors that determine the relationships between pharmacokinetic aspects of the disposition and metabolism of drugs and their therapeutic or toxic actions in man. Because of the more restricted information obtainable in human studies, this volume reflects the editors' bias that an understanding of pharmacokinetics is fundamental for assessing pharmacologic or toxicologic effects of drugs in humans. The first chapter is a unique primer on when to apply and how to use pharmaco kinetic tools in human pharmacology. The second chapter explains the general assumptions underlying pharmacokinetic approaches both in simple terms for the novice and in mathematical form for the more sophisticated reader. Several chapters on determinants of drug concentration and activity discuss drug absorption, drug latentiation, drugs acting through metabolites, entero hepatic drug circulation, influence of route of drug administration on response, genetic variations in drug disposition and response, age differences in absorption, distribution and excretion of drugs, and pathologic and physiologic factors affecting absorption, distribution and excretion of drugs and drug response. The focus of these chapters is data obtained in human, rather than animal, studies. Most of the chapters contain new material never summarized previously.