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Anatomy of the splanchnic, portal and hepatic venous circulation. (With permission: Gelman S, Mushlin PS. Catecholamine-induced changes in the splanchnic circulation affecting systemic hemodynamics. Anesthesiology 2004, 100: 434-439).
Source publication
Hepatosplanchnic circulation receives almost half of cardiac output and is essential to physiologic homeostasis. Liver cirrhosis is estimated to affect up to 1% of populations worldwide, including 1.5% to 3.3% of intensive care unit patients. Cirrhosis leads to hepatosplanchnic circulatory abnormalities and end-organ damage. Sepsis and cirrhosis re...
Context in source publication
Context 1
... valveless portal vein is a low- pressure/low-resistance system that provides partially deoxygenated blood from the intestinal bed to the liver, accounting for 70% of hepatic blood supply. Normal mean portal pressures range from 5-10 mmHg [21] ( Figure 1). Oxygen delivery to hepatocytes does not depend on the proportion of portal versus arterial blood flow [22] . ...
Citations
... Compared with the traditional caudate-right lobe ratio method, our proposed method is simple, accurate and robust, and has potential value in the diagnosis of cirrhosis. Liver fibrosis causes compression and irregular stenoses of the intrahepatic branches of the portal vein (23), and as a result, the blood supply transitions from the portal vein to the hepatic artery (24,25). The blood supply to the right lobe has more influence usually because the right portal vein enters the right lobe directly (23). ...
Background:
Early detection of liver cirrhosis is of great significance to the formulation of treatment plans and improving prognosis. Computed tomography (CT) is commonly used in the assessment of patients with chronic liver disease. In this study, we proposed a new distance ratio method for accurate diagnosis of cirrhosis using CT images.
Methods:
This was a retrospective study of a consecutive series of patients in Guangdong Provincial People's Hospital. Sixty-two patients with pathologically diagnosed cirrhosis but whose morphologic changes were insufficient to diagnose cirrhosis were included in the cirrhosis group. Those who were pathologically confirmed to be free of cirrhosis and fibrosis and without a history of chronic hepatic were classified as the control group. A total of 124 patients underwent abdominal dynamic enhanced CT. Both the L-distance ratio-the ratio of the distance from the right portal vein bifurcation point to the anterior and posterior edges of the liver-and the caudate-right lobe ratio were measured by two independent radiologists. Intraclass correlation coefficients (ICCs) were used to assess the agreement between the radiologists. Binary logistic regression was performed for univariate analysis, and the odds ratio (OR) was also calculated. The discrimination ability of the two methods was evaluated by the area under the receiver operating characteristic curve (AUC).
Results:
For both the L-distance ratio and the caudate-right lobe ratio, high agreement was observed between the two radiologists, although the ICC value of the L-distance ratio was slightly higher than that of the caudate-right lobe ratio (0.916 vs. 0.907). Binary logistic regression suggested that higher ratios were correlated with cirrhosis [the L-distance ratio, high vs. low OR =4.41, 95% confidence interval (CI): 2.08-9.36, P<0.001; the caudate-right lobe ratio, high vs. low OR =2.19, 95% CI: 1.07-4.49, P=0.031]. The AUCs of the L-distance ratio and the caudate-right lobe ratio were 0.823 (95% CI: 0.752-0.894) and 0.663 (95% CI: 0.569-0.757), respectively.
Conclusions:
The L-distance ratio method proposed in this paper is more simple, accurate, and reliable than the caudate-right lobe ratio method in the diagnosis of cirrhosis.
... Besides chylomicrons, lymphatics of the gastrointestinal tract transport molecules secreted by the mucosal mast cells when these cells are activated during fat absorption (Miller and Pemberton, 2002;Sato et al., 2016). Conversely, damage to the intestinal barrier leads to bacterial translocation, also in part via the mesentery, which may eventually cause liver inflammation and dysfunction, as well as exacerbation of circulatory abnormalities (Prin et al., 2015;de Jong et al., 2016). Likewise, in the previous studies of infectious liver disease caused by gut microorganisms, mesentery has been regarded as the main pathway for pathogenic bacteria to enter the liver, rather than the hepatic portal vein (O'Boyle et al., 1998). ...
The gut-liver axis denotes the intricate connection and interaction between gut microbiome and liver, in which compositional and functional shifts in gut microbiome affect host metabolism. Hepatic portal vein of the blood circulation system has been thought to be the major route for metabolite transportation in the gut-liver axis, but the existence and importance of other routes remain elusive. Here, we perform metabolome comparison in blood circulation and mesenteric lymph systems and identify significantly shifted metabolites in serum and mesentery. Using cellular assays, we find that the majority of decreased metabolites in lymph system under high-fat diet are effective in alleviating metabolic disorders, indicating a high potential of lymph system in regulating liver metabolism. Among those, a representative metabolite, L-carnitine, reduces diet-induced obesity in mice. Metabolic tracing analysis identifies that L-carnitine is independently transported by the mesenteric lymph system, serving as an example that lymph circulation comprises a second route in the gut-liver axis to modulate liver metabolism. Our study provides new insights into metabolite transportation via mesenteric lymph system in the gut-liver axis, offers an extended scope for the investigations in host-gut microbiota metabolic interactions and potentially new targets in the treatment of metabolic disorders.
... The liver is a blood-rich organ that draws 0.8-1.2 liters of blood per minute; the amount of blood contained in the liver represents about 20% of that within the whole body (4). For that reason, the control of blood loss is a crucial problem, especially during hepatectomy (5)(6)(7). ...
... The liver is at a central place in the mouse and human body metabolism: it sits at the junction between the intestinal portal vessels and the general circulation ( Figure 2) (Prin et al., 2015). This provides it with a unique position to sample all nutrients derived from the intestinal absorption but also to act as a first line of defence against pathogens, microbial-derived products and drugs derived from the gut. ...
Kupffer cells (KCs) are resident macrophages of the liver. Professional phagocytes of the innate immune system, they take part in the first line of defence against infections and injury. They also actively regulate liver homeostasis. Recent works have elucidated their origin. We now know that, like most other tissue resident macrophages, KCs develop during embryonic life from Erythro-Myeloid Progenitors (EMPs), seed the liver during development and persist there in adulthood. During inflammation, however, they can be joined by recently differentiated macrophages that arise from circulating monocytes belonging to the Haematopoietic Stem Cell (HSC) descendance. Here I studied the ability of mouse KCs to maintain themselves throughout life, and into old age. Using flow cytometry and fate mapping strategies, we showed that KC density decreased over time and was not compensated by recruitment of circulating cells. RNA sequencing, analysis of TicamLPS2 mutants and Poly (I:C)-induced repeated inflammation experiments highlighted the contribution of inflammation to the ageing phenotype. This phenotype correlated with lipid and senescent cell accumulation. We further studied KC maintenance in acetaminophen induced liver injury and after depletion induced by a CSF1R antagonist. In both contexts, KCs were able to maintain themselves through local proliferation without significant input from circulating cells. These experiments will provide a framework for the better characterisation of KC functions in injury and disease.
... Основной детерминантой ПГ при ЦП является увеличение сопротивления портальному потоку, в то время как увеличение притока играет второстепенную роль [9]. В печени с нормальной резистентностью при изменении портального кровотока давление в воротной вене не изменяется [10] из-за высокой степени податливости сосудов портальной системы. ...
Portal hypertension is the major consequences of liver cirrhosis and is accompanied by pathologic increase in portal blood flow resistance. As portal hypertension develops that results in formation of vessel's collaterals and arterial vasodilatation. Hyperdynamic alternations become more significant due to hyporesponsiveness to vasoconstrictors and increased shunts formation with autonomic neuropathy. This combination of liver failure and portal hypertension leads to the hyperdynamic circulatory state partly owing to simultaneous vasodilatation of splanchnic and peripheral arterial vessels. So hyperdynamic circulatory syndrome is a late complication of portal hypertension due to liver cirrhosis. The main features of hyperdynamic circulatory syndrome are high cardiac output, increased heart rate and total blood volume coupled with decreased total systemic vascular resistance. Some of these cardiovascular changes are reversible after liver transplantation what show pathophysiological significance of portal hypertension. In this paper, we aimed to review pathophysiology and features of hyperdynamic syndrome that are well-known and directly related to portal hypertension (varices, ascites, hepatic encephalopathy and hepatorenal syndrome), while others are more rare and therefore further investigations are necessary (portopulmonary hypertension, cirrhotic cardiomyopathy).
... Fischer rats being particularly susceptible to portal clamping, this strategy allows to obtain high survival rates despite the use of damaged grafts [6]. Spleno-systemic shunting in fact reduces splanchnic congestion and the consequent release of vasoplegic molecules responsible for shock after portal unclamping [20]. After surgery, recipient rats were kept in heated single cages for 12h with free access to food and water. ...
Hypothermic and normothermic ex vivo liver perfusions promote organ recovery after donation after circulatory death (DCD). We tested whether these perfusions can reduce the risk of hepatocellular carcinoma (HCC) recurrence in a 1h-DCD syngeneic transplantation model, using Fischer F344 rats. DCD grafts were machine perfused for 2h with hypothermic perfusion (HOPE) or normothermic perfusion (NORMO), and transplanted. After reperfusion, we injected HCC cells into the vena porta. On day 28 after transplantation, we assessed tumour volumes by MRI. Control rats included transplantations with Fresh and non-perfused DCD livers. We observed apoptotic-necrotic hepatocyte foci in all DCD grafts, which were more visible than in the Fresh liver grafts. Normothermic perfusion allowed a faster post-transplant recovery, with lower day 1 levels of transaminases compared with the other DCD. Overall, survival was similar in all four groups and all animals developed HCCs. Total tumor volume was lower in the Fresh liver recipients compared to the DCD and DCD+HOPE recipients. Volumes in DCD+NORMO recipients were not significantly different from those in the Fresh group. This experiment confirms that ischemia/reperfusion injury promotes HCC cell engraftment/growth after DCD liver transplantation. Using the present extreme 1h ischemia model, both hypothermic and normothermic perfusions were not effective in reducing this risk.
... As a consequence of the systemic circulatory dysregulation in cirrhotic patients characterized by a volume shift between central hypovolemia and peripheral hypervolemia, AVP is upregulated to compensate for this state [18]. The systemic inflammatory response syndrome (SIRS) and sepsis, which have similar effects on circulation [19], can deteriorate the existing circulatory impairment and worsen patients' prognosis. Hence, early diagnosis could improve outcomes. ...
Background
For many patients with end-stage liver disease, liver transplantation represents the only curative therapy. Transplant recipients are scored and ranked using the model for end-stage liver disease (MELD/MELD-Na). Circulatory impairment is known to deteriorate outcomes; however, it is not incorporated into the current allocation system’s score. The aim of our study is to analyze the predictive value of copeptin as a biomarker of circulatory impairment and increased short-term mortality risk in patients with end-stage liver disease.
Methods
We conducted a retrospective observational study of 615 patients with end-stage liver disease. Patients were recruited using assessments performed during the evaluation process for liver transplantation. Copeptin values were analyzed in comparison to MELD-Na, interleukin 6 (IL-6), and C-reactive protein (CRP).
Results
Elevated levels of copeptin, IL-6 and CRP, as well as high MELD-Na scores, were significantly correlated with mortality. In a comparison of copeptin-tertiles, patients in group T3 (16.3 pmol/L or more) showed a significantly higher mortality risk (hazard ratio 11.2, p < 0.001). After adjusting for MELD-Na, copeptin remains an independent predictor of mortality. It shows its greatest prognostic strength in short-term mortality, where it performs comparable to MELD-Na (AUROC for 7 day-mortality, 0.941/0.939; p = 0.981) and shows an additional predictive value to MELD-Na for short-term mortality (7 days, p: 0.046; 30 days, p: 0.006).
Conclusions
Copeptin presents a valuable individual biomarker in detecting patients at risk for short-term mortality. Further studies should be performed to confirm our findings.
... Hypoperfusion in the splanchnic region is considered one of the main reasons for mucosal gut barrier breakdown during sepsis (38). The splanchnic vasculature system normally receives about 25% of the total cardiac output, which increases up to 35% during digestion (60,61). Perfusion is mainly controlled by local mediators, including nitric oxide and prostaglandin derivatives, but also by systemic mediators, like vasoactive substance P and by the sympathetic innervation (61). ...
Sepsis is a complex of life-threating organ dysfunction in critically ill patients, with a primary infectious cause or through secondary infection of damaged tissues. The systemic consequences of sepsis have been intensively examined and evidences of local alterations and repercussions in the intestinal mucosal compartment is gradually defining gut-associated changes during sepsis. In the present review, we focus on sepsis-induced dysfunction of the intestinal barrier, consisting of an increased permeability of the epithelial lining, which may facilitate bacterial translocation. We discuss disturbances in intestinal vascular tonus and perfusion and coagulopathies with respect to their proposed underlying molecular mechanisms. The consequences of enzymatic responses by pancreatic proteases, intestinal alkaline phosphatases, and several matrix metalloproteases are also described. We conclude our insight with a discussion on novel therapeutic interventions derived from crucial aspects of the gut mucosal dynamics during sepsis.
... In fact, changes in bacterial translocation behavior along with a gradually attenuated hepatic clearance capacity for antigens-e.g., lipopolysaccharide "LPS" or endotoxin-boost systemic inflammatory activity through activation of various toll-like receptor (TLR) pathways and facilitate a massive production of cytokines [21]. This, in turn, results into elevated secretion of reactive oxygen species (ROS), which further enhance intestinal hyperpermeability and thus sustain a vicious circle of events widely known as "leaky gut" [22,23]. Meanwhile, a considerable amount of research efforts has been devoted to the development of therapies able to restore and maintain gut barrier integrity. ...
Liver cirrhosis yearly causes 1.2 million deaths worldwide, ranking as the 10th leading cause of death in the most developed countries. High susceptibility to infections along with a significant risk for infection-related mortality justifies the description of liver cirrhosis as the world’s most common immunodeficiency syndrome. Liver cirrhosis is an end-stage organic disease hallmarked by a multifaceted immune dysfunction due to deterioration of antimicrobial recognition and elimination mechanisms in macrophages along with an impaired antigen presentation ability in circulating monocytes. Bacterial translocation supports—and is supported by—uncontrolled activation of immune cell responses and/or loss of toll-like receptor (TLR) tolerance, which can turn exaggerated inflammatory responses to systemic inflammation. Lipopolysaccharide (LPS) or endotoxin boosts systemic inflammatory activity through activation of TLR-2- and TLR-4-dependent pathways and facilitate a massive production of cytokines. This, in turn, results into elevated secretion of reactive oxygen species (ROS), which further enhances intestinal hyperpermeability and thus sustains a vicious circle of events widely known as “leaky gut.” Albumin can be of particular benefit in cirrhotic patients with spontaneous bacterial peritonitis and/or hepatorenal syndrome type of acute kidney injury (HRS-AKI) due to anti-inflammatory and antioxidative stress as well as volume-expanding properties and endothelial-stabilizing attributes. However, presence of autoantibodies against albumin in patients with liver cirrhosis has been described. Although previous research suggested that these antibodies should be regarded as naturally occurring antibodies (NOA), the origin of the antialbumin immune response is obscure. High occurrence of NAO/albumin complexes in patients with liver disease might reflect a limited clearance capacity due to bypassing portal circulation. Moreover, high burden of oxidized albumin is associated with less favorable outcome in patients with liver cirrhosis. To date, there is no data available as to whether oxidized forms of albumin result in neoepitopes recognized by the immune system. Nevertheless, it is reasonable to hypothesize that these alterations may have the potential to induce antialbumin immune responses and thus favor systemic inflammation.
... However, according to the concept of blood flow heterogeneity in septic shock, a question arises: Is vasoconstriction present in all vascular pools in children with meningococcal septic shock? The greatest interest lies in the state of blood circulation in the organs of the splanchnic zone (intestines, liver), which is the largest vascular area and normally requires up to 25% of cardiac output and characterizes multiple aspects of homeostasis (Prin et al., 2015). There is an evident interest in the condition of the renal circulation, because damage and dysfunction of the kidneys and organs of the splanchnic zone are integral components of the multiple organ failure syndrome. ...
Meningococcal infection is caused by the bacterium Neisseria meningitidis (also termed meningococcus). Invasive meningococcal disease remains a rare infectious disease not only with high mortality but also with important morbidity and remains as a leading cause of sepsis and septic shock. The pathogenic mechanisms of microcirculatory disorders in meningococcal septic shock have been subject to controversy. This article presents the results of a study of 11 paediatric patients’ (4 boys and 7 girls) with meningococcal septic shock (Group I) who were hospitalized at the Regional Children's Infectious Hospital from 2009 to 2011. The average age of the patients was 37.4 ± 8.4 mo. Septic shock was diagnosed according to International Pediatric Sepsis Consensus Conference: definitions of criteria for sepsis and organ dysfunction in paediatrics. Heart rate, respiratory rate, systolic blood pressure, diastolic blood pressure, average blood pressure, SpO2 were monitored. The cardiac output, ejection fraction, fraction shortening, stroke volume were measured by ultrasound in M-mode by Teichholz method. Blood circulation in the a. mesenterica, a. hepatica, a. lienalis, a. renal sinister, v. porta, v. lienalis, v. renal sinister was determined by impulse Doppler’s wave. Acid-base and electrolytes level in serum, nitric oxide (NO), endothelin I, creatinine, C-reactivity protein and lactate blood level were measured. The control group consisted of 21 healthy children (9 boys and 12 girls), aged 37.5 ± 5.4 mo. in average (Group II). We used t-criteria (Student’s) and correlation with R-criteria (Spearmen) for statistical analysis. The data showed a statistically significant lower fraction of ejection, fraction of shortening, stroke volume in Group I. Moreover, our data showed a statistically high level of mesenterial and portal blood flow rate and high pulse index in v. renal sinister compared to healthy children. The blood level of NO was increased in Group I as well as in Group II. Direct correlations were determined between the level of NO and mesenteric, hepatic arterial and venous blood flow rate. Statistically significant inverse correlations between the level of NO and pulse resistive index in splanchnic vessels were discovered as well as inverse correlations between the NO level and the indicator of the severity of condition on PRISM scale (r = –0.952). At the same time, we have found no correlation between splanchnic circulation value and cardiac output. Based on the results of this study, we consider that NO has organ protective effects in children with meningococcal sepsis. Future research should aim to introduce new strategies of intensive care for patients with meningococcal septic shock with early use of inotrope and NO-donor therapy in fluid restriction combination.
