Clinical review: The liver in sepsis

During sepsis, the liver plays a key role. It is implicated in the host response, participating in the clearance of the infectious agents/products. Sepsis also induces liver damage through hemodynamic alterations or through direct or indirect assault on the hepatocytes or through both. Accordingly, liver dysfunction induced by sepsis is recognized as one of the components that contribute to the severity of the disease. Nevertheless, the incidence of liver dysfunction remains imprecise, probably because current diagnostic tools are lacking, notably those that can detect the early liver insult. In this review, we discuss the epidemiology, diagnostic tools, and impact on outcome as well as the pathophysiological aspects, including the cellular events and clinical picture leading to liver dysfunction. Finally, therapeutic considerations with regard to the weakness of the pertinent specific approach are examined.     

Management of sepsis in patients with liver failure

PURPOSE OF REVIEW: Sepsis constitutes the most common cause of death in the ICU. Liver dysfunction is manifested among previously normal subjects with sepsis but even more so in populations with preexisting liver disease. Managing these patients is more challenging. We will review recent literature in sepsis and liver disease, and their bedside application. RECENT FINDINGS: At the cellular-chemical level, studies showed that platelet aggregation and neutrophil activation occur before and are independent of microcirculatory changes which are apparent in all animal septic models. At the clinical level, early goal-directed therapy, euglycemia, low tidal volume ventilation, and early and appropriately dosed renal replacement therapy among others are all tools to improve sepsis survival. Acknowledgement of liver disease as an immunocompromised host, and identification and treatment of complications can positively change the outcome of sepsis in liver disease. SUMMARY: Much has been advanced in the field of sepsis management. Understanding the pathophysiology of liver dysfunction and decompensation of a diseased liver incites questions for future research. Early goal-directed therapy, lactate clearance, glycemic control, low volume ventilation strategies, nutrition, adrenal insufficiency, renal dysfunction, hepatorenal syndrome prevention and treatment are some of the issues in the management of sepsis, with or without liver disease, that are relevant in this review.     

Novel relationships between oxidative stress and angiogenesis-related factors in sepsis: New biomarkers and therapies

Abstract

Sepsis is a systemic uncontrolled inflammatory response in the presence of an infection. It remains a major cause of morbidity and mortality in hospitalized patients. According to its severity, sepsis can progress to three different states: severe sepsis, septic shock, and multiple organ dysfunction syndrome, related to organ dysfunction and/or tissue hypoperfusion. Different processes underlie its pathophysiology; among them are oxidative stress, endothelial and mitochondrial dysfunction, and angiogenesis-related factors. However, no studies have integrated these elements in sepsis. The main difficulty in sepsis is its diagnosis. Currently, the potential of inflammatory biomarkers in septic patients remains weak. In this context, the research into new biomarkers is essential to aid with sepsis diagnosis and prognostication. Furthermore, even though the current management of severe forms of sepsis has been effective, morbimortality remains elevated. Therefore, it is essential to explore alternative approaches to therapy development. The aim of this review is to present an update of evidence supporting the role of oxidative stress and angiogenesis-related factors in the pathophysiology of the different forms of sepsis. It proposes a novel convergence between both elements in their role in the disease, and it will cover their utility as new diagnostic tools, predictors of outcome, and as novel therapeutic targets.     

Myocardial depression in sepsis: From pathogenesis to clinical manifestations and treatment

The cardiovascular system plays a key role in sepsis, and septic myocardial depression is a common finding associated with increased morbidity and mortality. Myocardial depression during sepsis is not clearly defined, but it can perhaps be best described as a global (systolic and diastolic) dysfunction of both the left and right sides of the heart. The pathogenesis of septic myocardial depression involves a complex mix of systemic (hemodynamic) factors and genetic, molecular, metabolic, and structural alterations. Pulmonary artery catheterization and modern echo-Doppler techniques are important diagnostic tools in this setting. There are no specific therapies for septic myocardial depression, and the cornerstone of management is control of the underlying infectious process (adequate antibiotic therapy, removal of the source) and hemodynamic stabilization (fluids, vasopressor and inotropic agents). In this review, we will summarize the pathogenesis, diagnosis, and treatment of myocardial depression in sepsis. Additional studies are needed in order to improve diagnosis and identify therapeutic targets in septic myocardial dysfunction.     

Sepsis research in the next millennium: concentrate on the software rather than the hardware.

Today the basic principles of septic conditions are understood. Nevertheless, sepsis research has reached a critical point. To integrate our knowledge towards a consistent theory of the disease process and to derive effective therapies, new perspectives for future research that fit the complexity of the problem have to be found. We conducted a review of the literature concerning systemic inflammatory response syndrome (SIRS) and sepsis with particular reference to liver pathophysiology. And compared our findings with characteristic features of complex systems. The complexity of sepsis is broadly recognized. A review of the different aspects of liver inflammation during SIRS and sepsis, i.e. endotoxin challenge, cytokine induced dysfunction, the mechanisms of leukocyte transmigration, and hormonal and neuroendocrine regulatory mechanisms is given. Key aspects of complex systems, including parallelism, locality, emergence, and cross-scale interactions are introduced. We conclude that sepsis research needs new perspectives that allow us to handle the complex interactions occurring during the disease process. We propose to focus research on the interactions between the constituents of the system rather than only describing isolated aspects of the disease process. We also conclude that the ideas and techniques of non-linear systems theory are suitable tools for the analysis of complex and dynamic diseases like SIRS and sepsis.     

Sepsis-associated delirium

Objective Sepsis-associated delirium is a common and poorly understood neurological complication of sepsis. This review provides an update of the diagnostic criteria and treatment strategies and the current knowledge about the mechanisms involved in sepsis associated brain dysfunction. Data sources Articles published between 1981 and 2006 were identified through a Medline search for “encephalopathy” and “sepsis” and by hand searching of articles cited in the identified publications. The immune response to sepsis results in multiorgan failure including brain dysfunction. Discussion The potential mechanisms for sepsis-associated delirium include vascular damage, endothelial activation, breakdown of the blood-brain barrier, metabolic disorders, brain inflammation and apoptosis. On the other hand, there is evidence for distinct neuroprotective factors, such as anti-inflammatory mediators and glial cell activity. Conclusions The diagnosis of sepsis-associated delirium relies mainly on clinical and electrophysiological criteria, and its treatment is entirely based on general management of sepsis.     

Correlation of left ventricular systolic dysfunction determined by low ejection fraction and 30-day mortality in patients with severe sepsis and septic shock: A systematic review and meta-analysis

Introduction

The prognostic implications of myocardial dysfunction in patients with sepsis and its association with mortality are controversial. Several tools have been proposed to evaluate cardiac function in these patients, but their usefulness beyond guiding therapy is unclear. We review the value of echocardiographic estimate of left ventricular ejection fraction (LVEF) in the setting of severe sepsis and/or septic shock and its correlation with 30-day mortality.

Methods

We conducted a systematic review and meta-analysis to evaluate the prognostic functionality of newly diagnosed LV systolic dysfunction by transthoracic echocardiography on critical ill patients admitted to the intensive care unit with severe sepsis or septic shock.

Results

A search of EMBASE and PubMed, Ovide MEDLINE, and Cochrane CENTRAL medical databases yielded 7 studies meeting inclusion criteria reporting on a total of 585 patients. The pooled sensitivity of depressed LVEF for mortality was 52% (95% confidence interval [CI], 29%-73%), and pooled specificity was 63% (95% CI, 53%-71%). Summary receiver operating characteristic curve showed an area under the curve of 0.62 (95% CI, 0.58-0.67). The overall mortality diagnostic odd ratio for septic patients with LV systolic dysfunction was 1.92 (95% CI, 1.27-2.899). Statistical heterogeneity of studies was moderate.

Conclusion

The presence of new LV systolic dysfunction associated with sepsis and defined as low LVEF is neither a sensitive nor a specific predictor of mortality. These findings are limited because of the heterogeneity and underpower of the studies. Further research into this method is warranted.     

Cell death in sepsis: a matter of how, when, and where

Dysregulated cell death in several tissues is intimately involved in the pathogenesis of sepsis and contributes to multiple organ failure. Whether cell death during sepsis occurs by necrosis or apoptosis may depend on the cell type as well as the disease stage and is therefore a matter of intense debate. While lymphocyte apoptosis contributes to immunosuppression in sepsis, recent evidence suggests that necrosis of hepatocytes predominates in septic patients with liver dysfunction and correlates with poor survival. These distinct modes of cell death might have different consequences for the inflammatory response but are also critical for therapeutic interventions and the disease outcome. Understanding the complexity of death processes employing recently available serum biomarkers of cell death could lead to novel therapeutic approaches and assist in the steering of sepsis treatment.     

Harmful and protective roles of neutrophils in sepsis

The current studies demonstrate protective and harmful effects of neutrophils (PMN) during experimental sepsis after cecal ligation and puncture (CLP). It is known that CLP induces signaling defects in blood PMN. When PMN were depleted 12 h after CLP, there were dramatic reductions in levels of bacteremia, evidence for reduced liver and renal dysfunction, sharp reductions in serum levels of cytokines (IL-1beta, IL-6, IL-10, TNF-alpha, and IL-2), and improved survival. In contrast, PMN depletion before CLP resulted in substantial increases in bacteremia and no evidence for attenuation of liver and renal failure dysfunction. These data suggest that at the onset of sepsis, PMN are important in regulating the levels of bacteremia, whereas after the onset of sepsis, as they lose innate immune functions, their presence is associated with higher levels of bacteremia and intensified organ dysfunction.     

Advances in the understanding of clinical manifestations and therapy of severe sepsis: an update for critical care nurses.

Severe sepsis is a major public health concern and a burden on the healthcare system. Despite improvements in efforts to control the source of infection and increased recognition by healthcare providers of patients with the disease, the mortality rate remains unacceptably high, from 30% to 50%. The systemic inflammatory response syndrome criteria are used as diagnostic indicators of sepsis when they occur in patients with known or suspected infection. The outcome of a patient with severe sepsis is often related to the occurrence of sepsis-induced multiple organ dysfunction syndrome. Multiple organ dysfunction syndrome appears to result from a cascade of organism-related factors, inflammatory mediators, endothelial injury, disturbed hemostasis, and microcirculatory abnormalities. In patients with severe sepsis, derangements of inflammation and coagulation are tightly linked. Although numerous clinical trials focused on interventions in one or the other of the inflammatory and coagulation systems failed to show reduced mortality due to sepsis, a member of a new class of drugs called "cogins" was effective. In its active form, protein C has anti-inflammatory, antithrombotic, and profibrinolytic properties that can reduce organ injury associated with severe sepsis. A recombinant form of activated protein C, drotrecogin alfa (activated), significantly reduces 28-day mortality due to all causes in patients with severe sepsis and has an acceptable safety profile. This review provides an overview of severe sepsis, highlighting recent advances in treatment of the disease and the role of critical care nurses.     

How to approach genome wars in sepsis?

Sepsis continues to pose a clear challenge as one of the most difficult and costly problems to treat and prevent. Sepsis is caused by systemic or localized infections that damage the integrity of microcirculation in multiple organs. The challenge of sepsis and its long-term sequelae was addressed by the National Institutes of Health National Heart Lung and Blood Institute Division of Blood Diseases and Resources. Defining sepsis as severe endothelial dysfunction syndrome that causes multiorgan failure in response to intravascular or extravascular microbial agents, the National Heart Lung and Blood Institute panel proposed the concept of genome wars as a platform for new diagnostic, therapeutic, and preventive approaches to sepsis.     

The applications of B-type natriuretic peptide measurement in the intensive care unit

PURPOSE OF REVIEW: Plasma B-type natriuretic peptide levels are used to screen for cardiac dysfunction in the emergency department and outpatient population. However, in the critically ill patient elevated plasma B-type natriuretic peptide levels do not necessarily reflect just ventricular dysfunction, as there are important confounding factors to consider. This review summarizes the recent advances in the application of B-type natriuretic peptide measurement in the intensive care unit. RECENT FINDINGS: B-Type natriuretic peptide levels are very useful in identifying cardiac dysfunction but not the specific pathology, whether it is right or left ventricular failure, diastolic or systolic dysfunction. Elevated serum B-type natriuretic peptide levels also occur in severe sepsis or septic shock. It also predicts cardiac dysfunction in sepsis. The lack of correlation of B-type natriuretic peptide concentrations with filling pressures in the intensive care unit precludes its use for monitoring cardiac therapy. Some studies involving patients with sepsis or septic shock demonstrate a positive correlation with mortality, while others failed to establish such a relation. The prognostic value of B-type natriuretic peptide in predicting mortality and morbidity remains controversial, partly due to different study designs. SUMMARY: B-Type natriuretic peptide is potentially a very useful diagnostic tool in the intensive care unit. To date there have been few studies and the results are often contradictory, mainly due to the special setting of the intensive care unit, which is constantly exposed to hemodynamically unstable patients, different case mixes as well as vigorous treatments. All of these are potential confounders to B-type natriuretic peptide levels and make interpretations of B-type natriuretic peptide difficult. We need more research on these confounding factors to accentuate the positive value of B-type natriuretic peptide in the intensive care unit.     

-反方观点-全身性感染新定义：不利于早期识别和早期治疗

全身性感染的定义自1992年发布以来,经过2001年的更新,其内容在这二十多年间并没有实质性调整。基于最新的大样本临床数据分析,全身性感染新定义特别小组重新定义了全身性感染,并提出了新的临床诊断标准。然而新定义中特别强调的器官功能障碍却成为其自相矛盾的根源;将全身性感染相关性器官功能衰竭评分（sepsis related organ failure assessment,SOFA）作为新的诊断标准也面临着与全身炎症反应综合征（systemic inflammatory response syndrome,SIRS）标准相同的问题;全身性感染中真正难以解决的问题仍然存在。因此,在对全身性感染的病理生理机制尚未有重大突破性进展时,就轻易改变现有的定义/临床标准框架,并没有太多实质性的意义。     

The liver in sepsis: shedding light on the cellular basis of hepatocyte dysfunction

Liver dysfunction is believed to contribute to the metabolic derangements of critical illness. The cellular basis of liver dysfunction is poorly understood and its consequences largely unknown. Recent work by Gonnert and colleagues sheds additional light. Using two imaging techniques to track the clearance of biotransformed dyes by the liver in a rat model of intra-abdominal infection, the authors show that the predominant defect in sepsis lies in the excretion of biotransformed molecules from the hepatocyte into the bile canaliculi. Their work both points to a new aspect of hepatic dysfunction through focus on a role in the metabolic derangements of sepsis and suggests a possible strategy to diagnose and monitor this process in critically ill patients.A new report by Gonnert and co-workers from the Center for Sepsis Control and Care in Jena Germany, recently appearing in Critical Care, provides important new insight into the nature and mechanisms of hepatocellular dysfunction in sepsis [1]. Since Bywaters first described the phenomenon of jaundice following severe trauma in 1946 [2], liver dysfunction has been considered a prominent feature of the Multiple Organ Dysfunction Syndrome and has been defined predominantly by hyperbilirubinemia and clinical jaundice [3-6]. The liver, however, is an enormously complex organ whose function is difficult to characterize succinctly or comprehensively. The liver plays a critical role in protein synthesis, in intermediary metabolism, and in the excretion of toxins and wastes, including the breakdown products of senescent red cells; this latter role is reflected in the widespread use of bilirubin levels as a measure of hepatic dysfunction. However, the liver is also involved in hematopoiesis during embryologic development, in innate immunity, and in digestion through the production of bile.Yet we understand little about how liver function is altered during critical illness, and how these alterations are best measured. Hyperbilirubinemia, the classic marker of hepatic dysfunction, provides little insight into what is happening within the liver. The prevalence of hyperbilirubinemia appears to be on the decline, perhaps because of declining use of total parenteral nutrition and of transfusion, although it is an independent risk factor for increased mortality [7,8]. Moreover, the presence and prognostic import of hyperbilirubinemia appear to derive more from the fact that this marker delineates a population of patients with irreversible end-stage liver disease rather than a transient and potentially reversible process that might be considered a component of the Multiple Organ Dysfunction Syndrome. Greater insight into other aspects of hepatic dysfunction that might be both deranged in critical illness and measured in critically ill patients is clearly needed.The Jena group is making substantial strides in addressing this need, and is bringing attention to striking abnormalities in hepatic biotransformation and excretion that arise in severely ill patients [9]. They have shown previously that hepatocellular transport at the canalicular pole of the hepatocyte is impaired in sepsis, with the result that a spectrum of hepatotoxic materials accumulates within the septic liver. They now extend these important observations [1].Gonnert and colleagues use a combination of elegant imaging techniques to detect clearance of two dyes that are metabolized by the liver - indocyanine green and DY635 - in a lethal rat model of intra-abdominal infection resulting from intraperitoneal administration of feces. They show that dye is cleared from the circulation and taken up readily by liver cells, but that its appearance in bile is delayed, indicating that defective cellular function primarily involves excretion of transformed molecules from the hepatocyte into the biliary canaliculi, rather than its delivery to, or uptake by, liver cells. Impaired excretion of dye is further evidenced as sustained persistence of dye within the liver, and its reduced appearance within the lumen of the gastrointestinal tract.This body of work and the ongoing evolution of the authors'' investigations hold exciting and important possibilities. First, the work provides valuable insight into the nature of hepatocellular dysfunction in critical illness, shifting the focus from microcirculatory impairments or abnormalities in uptake of hepatically transformed compounds to their excretion into the biliary tree and gastrointestinal tract. The significance of accumulation of a spectrum of compounds - toxins, drugs, bilirubin, and other metabolic substances - within the hepatocyte is uncertain, and is fertile ground for future study. Does their accumulation subsequently result in impaired uptake from the liver microvasculature? If so, then toxins or drugs may accumulate in the circulation, their normal metabolism impeded by failure of their excretion from the hepatocyte. If this is the case, then those alterations may be modifiable by altering drug doses or by extracorporeal removal, and eventually by pharmacologic interventions that correct the excretory derangement. Does impaired hepatocellular excretion affect the normal synthetic function of the hepatocyte, and therefore impair its ability to synthesize proteins such as acute phase reactants or coagulation factors? Does impaired excretion alter the ability of the liver to take up glucose and store it as glycogen, and therefore may hepatocellular dysfunction emerge as a component of the syndrome of insulin resistance that is so commonly seen in sepsis? Do alterations in hepatocyte function result in altered Kupffer cell function, and therefore contribute to the immunologic alterations of sepsis?Moreover, as techniques of near-infrared fluorescence imaging improve, the technologies described by Gonnert and colleagues may well find a clinical role as a noninvasive test of hepatic dysfunction in the critically ill patient, and so provide a measure of liver function that is more sensitive, sophisticated, and relevant than the serum bilirubin level.Despite its fundamental and varied role in normal homeostasis, to the intensivist the liver remains a frustratingly opaque black box whose inner workings are obscure. Studies like those of Gonnert and colleagues are beginning to lift the lid, if only a little, and to shine a light on a largely unexplored area in the support of the critically ill patient.     

Severe hypocholesterolemia in surgical patients,sepsis, and critical illness

After surgery, in sepsis and various critical illnesses, factors such as severity of the acute phase response, liver dysfunction, and hemodilution from blood loss have cumulative impacts in decreasing cholesterol; therefore, degree of hypocholesterolemia often reflects severity of illness. The direct correlation between cholesterol and several plasma proteins is mediated by the parallel impact of commonly shared determinants. Cholestasis is associated with a moderation of the degree of hypocholesterolemia. In human sepsis, the poor implications of hypocholesterolemia seem to be aggravated by the simultaneous development of hypertriglyceridemia. Cholesterol and triglyceride levels reflect altered lipoprotein patterns, and the issue is too complex and too poorly understood to be reduced to simple concepts; nevertheless, these simple measurements often represent helpful adjunctive clinical tools.     

Nonalcoholic steatohepatitis: recent advances from experimental models to clinical management

A condition defined as nonalcoholic fatty liver disease (NAFLD) is frequently found in humans. Deemed as a benign condition until recently, more emphasis is now put on the potential harmful evolution of the inflammatory form, that is, nonalcoholic steatohepatitis (NASH), toward end-stage liver disease. This review highlights the major morphologic and pathophysiological features of NASH. The link between experimental biochemical findings in animal models and clinical and therapeutic approaches in humans is discussed. Once all the other causes of persistent elevation of serum transaminase levels have been excluded, the diagnosis of NASH can be only confirmed by liver histology. Other noninvasive diagnostic tools, however, are being investigated to assess specific subcellular functions and to allow the follow-up of patients at higher risk for major liver dysfunction. A better understanding of various pathogenic aspects of NASH will help in identifying potential therapeutic approaches in these patients.     

The hematologic system as a marker of organ dysfunction in sepsis

Sepsis with acute organ dysfunction (severe sepsis) results from a systemic proinflammatory and procoagulant response to infection. Organ dysfunction in the patient with sepsis is associated with increased mortality. Although most organs have discrete anatomical boundaries and carry out unified functions, the hematologic system is poorly circumscribed and serves several unrelated functions. This review addresses the hematologic changes associated with sepsis and provides a framework for prompt diagnosis and rational drug therapy. Data sources used include published research and review articles in the English language related to hematologic alterations in animal models of sepsis and in critically ill patients. Hematologic changes are present in virtually every patient with severe sepsis. Leukocytosis, anemia, thrombocytopenia, and activation of the coagulation cascade are the most common abnormalities. Despite theoretical advantages of using granulocyte colony-stimulating factor to enhance leukocyte function and/or circulating numbers, large clinical trials with these growth factors are lacking. Recent studies support a reduction in the red blood cell transfusion threshold and the use of erythropoietin treatment to reduce transfusion requirements. Treatment of thrombocytopenia depends on the cause and clinical context but may include platelet transfusions and discontinuation of heparin or other inciting drugs. The use of activated protein C may provide a survival benefit in subsets of patients with severe sepsis. The hematologic system should not be overlooked when assessing a patient with severe sepsis. A thorough clinical evaluation and panel of laboratory tests that relate to this organ system should be as much a part of the work-up as taking the patient's blood pressure, monitoring renal function, or measuring liver enzymes.     

Role of international normalized ratio in nonpulmonary sepsis screening: An observational study

BACKGROUNDCurrently, there is a lack of sepsis screening tools that can be widely used worldwide. Pulmonary sepsis can be of sufficient concern to physicians due to their noticeable symptoms, which usually rely less on screening tools. AIMTo investigate the efficiency of the international normalized ratio (INR) for the early rapid recognition of adult nonpulmonary infectious sepsis.METHODSThis is a prospective observational study. A total of 108 sepsis patients and 106 nonsepsis patients were enrolled according to relevant inclusion and exclusion criteria. Commonly used clinical indicators, such as white blood cell, neutrophil count, lymphocyte count, neutrophil-lymphocyte count ratio (NLCR), platelets (PLT), prothrombin time, INR, activated partial thromboplastin time, and quick Sequential “Sepsis-related” Organ Failure Assessment (qSOFA) scores were recorded within 24 h after admission. The diagnostic performances of these clinical indicators were analyzed and compared through multivariate logistic regression analysis, Spearman correlation, and receiver operating characteristic curve analysis. RESULTSThe INR value of the sepsis group was significantly higher than that of the nonsepsis group. INR has superior diagnostic efficacy for sepsis, with an area under the curve value of 0.918, when those preexisting diseases which significantly affect coagulation function were excluded. The diagnostic efficacy of the INR was more significant than that of NLCR, PLT, and qSOFA (P < 0.05). Moreover, INR levels of 1.17, 1.20, and 1.22 could be used to categorize the relative risk of nonpulmonary infections sepsis into three categories: low, medium and high risk, respectively. CONCLUSIONThe INR is a promising and easily available biomarker for diagnosis, and it can be used as one of the indicators for early screening of adult nonpulmonary infectious sepsis. When its value is higher than the optimal cutoff value (1.22), high vigilance is required for adult nonpulmonary infectious sepsis.     

Microvascular endothelial dysfunction: a renewed appreciation of sepsis pathophysiology

Severe sepsis, defined as sepsis associated with acute organ dysfunction, results from a generalized inflammatory and procoagulant host response to infection. Coagulopathy in severe sepsis is commonly associated with multiple organ dysfunction, and often results in death. The molecule that is central to these effects is thrombin, although it may also have anticoagulant and antithrombotic effects through the activation of Protein C and induction of prostacyclin. In recent years, it has been recognized that chemicals produced by endothelial cells play a key role in the pathogenesis of sepsis. Thrombomodulin on endothelial cells coverts Protein C to Activated Protein C, which has important antithrombotic, profibrinolytic and anti-inflammatory properties. A number of studies have shown that Protein C levels are reduced in patients with severe infection, or even in inflammatory states without infection. Because coagulopathy is associated with high mortality rates, and animal studies have indicated that therapeutic intervention may result in improved outcomes, it was rational to initiate clinical studies.     

Effects of prolonged endotoxemia on liver, skeletal muscle and kidney mitochondrial function

Introduction  

Sepsis may impair mitochondrial utilization of oxygen. Since hepatic dysfunction is a hallmark of sepsis, we hypothesized that the liver is more susceptible to mitochondrial dysfunction than the peripheral tissues, such as the skeletal muscle. We studied the effect of prolonged endotoxin infusion on liver, muscle and kidney mitochondrial respiration and on hepatosplanchnic oxygen transport and microcirculation in pigs.