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Nature Reviews. Gastroenterology &... Apr 2019The liver microcirculatory milieu, mainly composed of liver sinusoidal endothelial cells (LSECs), hepatic stellate cells (HSCs) and hepatic macrophages, has an essential... (Review)
Review
The liver microcirculatory milieu, mainly composed of liver sinusoidal endothelial cells (LSECs), hepatic stellate cells (HSCs) and hepatic macrophages, has an essential role in liver homeostasis, including in preserving hepatocyte function, regulating the vascular tone and controlling inflammation. Liver microcirculatory dysfunction is one of the key mechanisms that promotes the progression of chronic liver disease (also termed cirrhosis) and the development of its major clinical complication, portal hypertension. In the present Review, we describe the current knowledge of liver microcirculatory dysfunction in cirrhotic portal hypertension and appraise the preclinical models used to study the liver circulation. We also provide a comprehensive summary of the promising therapeutic options to target the liver microvasculature in cirrhosis.
Topics: Combined Modality Therapy; Humans; Hypertension, Portal; Liver Circulation; Microcirculation; Vascular Resistance
PubMed: 30568278
DOI: 10.1038/s41575-018-0097-3 -
WIREs Mechanisms of Disease Mar 2023The function of the liver depends critically on its blood supply. Numerous in silico models have been developed to study various aspects of the hepatic circulation,... (Review)
Review
The function of the liver depends critically on its blood supply. Numerous in silico models have been developed to study various aspects of the hepatic circulation, including not only the macro-hemodynamics at the organ level, but also the microcirculation at the lobular level. In addition, computational models of blood flow and bile flow have been used to study the transport, metabolism, and clearance of drugs in pharmacokinetic studies. These in silico models aim to provide insights into the liver organ function under both healthy and diseased states, and to assist quantitative analysis for surgical planning and postsurgery treatment. The purpose of this review is to provide an update on state-of-the-art in silico models of the hepatic circulation and transport processes. We introduce the numerical methods and the physiological background of these models. We also discuss multiscale frameworks that have been proposed for the liver, and their linkage with the large context of systems biology, systems pharmacology, and the Physiome project. This article is categorized under: Metabolic Diseases > Computational Models Metabolic Diseases > Biomedical Engineering Cardiovascular Diseases > Computational Models.
Topics: Liver Circulation; Liver; Computer Simulation; Bile; Hemodynamics
PubMed: 36131627
DOI: 10.1002/wsbm.1586 -
Seminars in Pediatric Surgery Nov 2013In the neonate, the liver is relatively immature and undergoes several changes in its functional capacity during the early postnatal period. The essential liver... (Review)
Review
In the neonate, the liver is relatively immature and undergoes several changes in its functional capacity during the early postnatal period. The essential liver functions can be classified into three categories: metabolism, detoxification, and bile synthesis. In general, the immature liver function has limited consequences on the healthy term neonate. However, preterm neonates are particularly susceptible to the effects of the immature liver function placing them at risk of hypoglycemia, hyperbilirubinemia, cholestasis, bleeding, and impaired drug metabolism. An appreciation of the dynamic changes in liver function during the neonatal period is essential for successful management of neonates who require medical and surgical interventions. This review will focus on the neonatal liver function as well as the changes that the liver undergoes as it matures.
Topics: Biotransformation; Humans; Infant, Newborn; Liver; Liver Circulation; Organogenesis
PubMed: 24331092
DOI: 10.1053/j.sempedsurg.2013.10.006 -
Pharmacology & Therapeutics 1990In recent years, knowledge of the physiology and pharmacology of hepatic circulation has grown rapidly. Liver microcirculation has a unique design that allows very... (Review)
Review
In recent years, knowledge of the physiology and pharmacology of hepatic circulation has grown rapidly. Liver microcirculation has a unique design that allows very efficient exchange processes between plasma and liver cells, even when severe constraints are imposed upon the system, i.e. in stressful situations. Furthermore, it has been recognized recently that sinusoids and their associated cells can no longer be considered only as passive structures ensuring the dispersion of molecules in the liver, but represent a very sophisticated network that protects and regulates parenchymal cells through a variety of mediators. Finally, vascular abnormalities are a prominent feature of a number of liver pathological processes, including cirrhosis and liver cell necrosis whether induced by alcohol, ischemia, endotoxins, virus or chemicals. Although it is not clear whether vascular lesions can be the primary events that lead to hepatocyte injury, the main interest of these findings is that liver microcirculation could represent a potential target for drug action in these conditions.
Topics: Animals; Humans; Liver; Liver Circulation; Liver Diseases
PubMed: 2203072
DOI: 10.1016/0163-7258(90)90091-f -
Hepatology (Baltimore, Md.) Feb 2008Blood circulating from the intestines to the liver is rich in bacterial products, environmental toxins, and food antigens. To effectively and quickly defend against... (Review)
Review
UNLABELLED
Blood circulating from the intestines to the liver is rich in bacterial products, environmental toxins, and food antigens. To effectively and quickly defend against potentially toxic agents without launching harmful immune responses, the liver relies on its strong innate immune system. This comprises enrichment of innate immune cells (such as macrophages, natural killer, natural killer T, and gammadelta T cells) and removal of waste molecules and immunologic elimination of microorganisms by liver endothelial cells and Kupffer cells. In addition, the liver also plays an important role in controlling systemic innate immunity through the biosynthesis of numerous soluble pathogen-recognition receptors and complement components.
CONCLUSION
The liver is an organ with predominant innate immunity, playing an important role not only in host defenses against invading microorganisms and tumor transformation but also in liver injury and repair. Recent evidence suggests that innate immunity is also involved in the pathogenesis of liver fibrosis, providing novel therapeutic targets to treat such a liver disorder.
Topics: Animals; Complement Activation; Complement System Proteins; Hepatocytes; Humans; Immunity, Innate; Killer Cells, Natural; Kupffer Cells; Liver; Liver Circulation; T-Lymphocytes
PubMed: 18167066
DOI: 10.1002/hep.22034 -
Journal of Hepatology Apr 2008Serotonin or 5-hydroxytryptamine (5-HT) is known to regulate several key aspects of liver biology and these functions include hepatic blood flow, innervation and wound... (Review)
Review
Serotonin or 5-hydroxytryptamine (5-HT) is known to regulate several key aspects of liver biology and these functions include hepatic blood flow, innervation and wound healing. Given the importance of these functions it is surprising that relatively little time has been dedicated to studying the precise function and mechanisms of serotonin within the liver. Here we describe what is known about serotonin and the liver and those receptor types that mediate the observed effects with an aim to stimulating new interest in the field of serotonin and liver biology.
Topics: Animals; Humans; Liver; Liver Circulation; Serotonin
PubMed: 18280000
DOI: 10.1016/j.jhep.2008.01.006 -
Clinics in Liver Disease Feb 2011The dual blood supply of the liver, originating from the portal vein and the hepatic artery, makes it relatively resistant to minor circulatory disturbances. However,... (Review)
Review
The dual blood supply of the liver, originating from the portal vein and the hepatic artery, makes it relatively resistant to minor circulatory disturbances. However, hepatic manifestations of common cardiovascular disorders are frequently encountered in both the inpatient and outpatient setting. Beginning with the macro- and microcirculation of the liver, this article reviews the pathophysiology of hepatic blood flow and gives a detailed appraisal of ischemic hepatitis, congestive hepatopathy, and other less common hepatic conditions that arise when cardiovascular function is impaired.
Topics: Cardiovascular Diseases; Female; Hepatic Artery; Humans; Liver; Liver Circulation; Liver Diseases; Male; Portal Vein
PubMed: 21111990
DOI: 10.1016/j.cld.2010.09.010 -
The Veterinary Quarterly Jun 1995This paper presents a review of the literature on hepatic circulation and circulatory disorders of the liver in the dog and cat, and also includes a number of our own... (Review)
Review
This paper presents a review of the literature on hepatic circulation and circulatory disorders of the liver in the dog and cat, and also includes a number of our own not previously published data. Circulatory disorders of the liver are frequently observed in dogs and cats. These disorders can be divided into congenital portosystemic shunts, disorders associated with outflow disturbances, and disorders associated with portal hypertension. Outflow disturbances result in passive congestion of the liver and in both species are mainly due to cardiac failure. Portal hypertension with resultant portosystemic collateral circulation and ascites mainly results from chronic liver disease, particularly cirrhosis. The main vascular disorder resulting in portal hypertension and ascites in the dog is primary hypoplasia of the portal vein.
Topics: Animals; Cat Diseases; Cats; Dog Diseases; Dogs; Liver Circulation; Liver Diseases
PubMed: 7571284
DOI: 10.1080/01652176.1995.9694536 -
Clinical Pharmacokinetics Nov 1999Liver disease can modify the kinetics of drugs biotransformed by the liver. This review updates recent developments in this field, with particular emphasis on cytochrome... (Review)
Review
Liver disease can modify the kinetics of drugs biotransformed by the liver. This review updates recent developments in this field, with particular emphasis on cytochrome P450 (CYP). CYP is a rapidly expanding area in clinical pharmacology. The information currently available on specific isoforms involved in drug metabolism has increased tremendously over the latest years, but knowledge remains incomplete. Studies on the effects of liver disease on specific isoenzymes of CYP have shown that some isoforms are more susceptible than others to liver disease. A detailed knowledge of the particular isoenzyme involved in the metabolism of a drug and the impact of liver disease on that enzyme can provide a rational basis for dosage adjustment in patients with hepatic impairment. The capacity of the liver to metabolise drugs depends on hepatic blood flow and liver enzyme activity, both of which can be affected by liver disease. In addition, liver failure can influence the binding of a drug to plasma proteins. These changes can occur alone or in combination; when they coexist their effect on drug kinetics is synergistic, not simply additive. The kinetics of drugs with a low hepatic extraction are sensitive to hepatic failure rather than to liver blood flow changes, but drugs having a significant first-pass effect are sensitive to alterations in hepatic blood flow. The drugs examined in this review are: cardiovascular agents (angiotensin converting enzyme inhibitors, angiotensin II receptor antagonists, calcium antagonists, ketanserin, antiarrhythmics and hypolipidaemics), diuretics (torasemide), psychoactive and anticonvulsant agents (benzodiazepines, flumazenil, antidepressants and tiagabine), antiemetics (metoclopramide and serotonin antagonists), antiulcers (acid pump inhibitors), anti-infectives and antiretroviral agents (grepafloxacin, ornidazole, pefloxacin, stavudine and zidovudine), immunosuppressants (cyclosporin and tacrolimus), naltrexone, tolcapone and toremifene. According to the available data, the kinetics of many drugs are altered by liver disease to an extent that requires dosage adjustment; the problem is to quantify the required changes. Obviously, this requires the evaluation of the degree of hepatic impairment. At present there is no satisfactory test that gives a quantitative measure of liver function and its impairment. A critical evaluation of these methods is provided. Guidelines providing a rational basis for dosage adjustment are illustrated. Finally, it is important to consider that liver disease not only affects pharmacokinetics but also pharmacodynamics. This review also examines drugs with altered pharmacodynamics.
Topics: Animals; Humans; Liver Circulation; Liver Diseases; Liver Function Tests; Pharmaceutical Preparations; Pharmacokinetics
PubMed: 10589374
DOI: 10.2165/00003088-199937050-00004 -
Canadian Journal of Physiology and... Aug 1987This article describes hepatic circulatory disturbances associated with anesthesia and surgical intervention. The material is presented in three parts: part 1 describes... (Review)
Review
This article describes hepatic circulatory disturbances associated with anesthesia and surgical intervention. The material is presented in three parts: part 1 describes the effects of general anesthetics on the hepatic circulation; part 2 deals with different factors related to surgical procedures and anesthesia; and part 3 analyzes the role of hepatic circulatory disturbances and hepatic oxygen deprivation in anesthesia-induced hepatotoxicity. The analysis of available data suggests that general anesthesia affects the splanchnic and hepatic circulation in various directions and to different degrees. The majority of anesthetics decreases portal blood flow in association with a decrease in cardiac output. However, hepatic arterial blood flow can be preserved, decreased, or increased. The increase in hepatic arterial blood flow, when it occurs, is usually not enough to compensate for a decrease in portal blood flow and therefore total hepatic blood flow is usually decreased during anesthesia. This decrease in total hepatic blood flow has certain pharmacokinetic implications, namely a decrease in clearance of endogenous and exogenous substances with a high hepatic extraction ratio. On the other hand, a reduction in the hepatic oxygen supply might play a certain role in liver dysfunction occurring perioperatively. Surgical procedures-preparations combined with anesthesia have a very complex effect on the splanchnic and hepatic circulation. Within this complex, the surgical procedure-preparation plays the main role in developing circulatory disturbances, while anesthesia plays only a modifying role. Hepatic oxygen deprivation may play an important role in anesthesia-induced hepatotoxicity in different experimental models.
Topics: Anesthesia, General; Anesthetics; Animals; Humans; Liver Circulation
PubMed: 3319112
DOI: 10.1139/y87-276