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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepatic encephalopathy (HE) in acute liver injury signifies a serious prognosis. Brain edema and intracranial hypertension are major causes of death in this syndrome. Comparison of HE in acute liver failure (ALF) with that of cirrhosis allows recognition of important differences and similarities. A key role for ammonia in the pathogenesis of both HE and brain edema is now firmly supported by clinical and experimental data. Additional factors, such as infection, products of the necrotic liver, and synergistic toxins, may contribute to an altered mental state. A low plasma osmolarity, high temperature, and both high and low arterial pressure may affect brain water content. A combined derangement of cellular osmolarity coupled with cerebral hyperemia can explain the development of brain edema in ALF. Increasingly, study of the mechanisms responsible for brain swelling provides critical information for understanding the pathogenesis of HE.
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PMID:Pathogenesis of hepatic encephalopathy in acute liver failure. 1452 79

Increased intracranial pressure (ICP) in patients with acute liver failure (ALF) remains a major cause of morbidity and mortality. Conventional methods of ammonia reduction such as the use of lactulose do not improve outcome, and metabolic substrates such as L-ornithine L aspartate may offer more promise. Mannitol remains the mainstay of therapy. An important role for cerebral hyperemia in the pathogenesis of increased ICP has led to a reevaluation of established therapies such as hyperventilation, N-acetylcysteine, thiopentone sodium, and propofol. Recent studies have focused on the role of systemic inflammatory response in the pathogenesis of increased ICP and support the use of antibiotics prophylactically. Moderate hypothermia reduces ICP in patients with uncontrolled intracranial hypertension and prevents increases in ICP during orthotopic liver transplantation (OLT). Advances in understanding the pathophysiological basis of intracranial hypertension in ALF have outstripped appropriate testing of the newly generated ideas in appropriate clinical trials, and more effort should be mounted at a national level to organize the appropriate multicenter studies required.
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PMID:Intracranial hypertension in acute liver failure: pathophysiological basis of rational management. 1452 80

Hepatic encephalopathy and brain edema are important complications in the course of a patient with acute liver failure. Presumed unrelated for many years, increasing evidence suggests that an increase in brain water is seen in all forms of hepatic encephalopathy. Ammonia, traditionally linked to the pathogenesis of hepatic encephalopathy, plays an important role in the increase in brain water. In acute liver failure, an osmotic disturbance in the astrocyte, in combination with an alteration of cerebral blood flow results in overt brain edema and intracranial hypertension. In cirrhosis, magnetic resonance techniques indicate the presence of a brain osmotic disturbance. Several clinical factors modulate the development of brain swelling.
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PMID:Brain edema in acute liver failure. A window to the pathogenesis of hepatic encephalopathy. 1509 1

Arterial hyperammonemia and cerebral vasodilatation correlate with cerebral herniation in patients with fulminant hepatic failure (FHF). Tacrolimus is a calcineurin inhibitor that passes the blood-brain barrier and may increase cerebrovascular tone and restrict cerebral ammonia influx. In this study, we determined if tacrolimus prevents cerebral vasodilatation and high intracranial pressure (ICP) in the rat with portacaval anastomosis (PCA) challenged to high arterial ammonia (NH4+) concentration. Seven groups of mechanically ventilated rats, with 6-9 rats in each group, were investigated within 48 hours after construction of a PCA (4 groups) or after sham operation (3 groups). Three groups of the rats received infusion of NH4+ and 4 groups received saline for approximately 180 minutes. Two groups of the PCA rats receiving either NH4+ or saline had an i.v. injection of tacrolimus (0.4 mg/kg) or vehicle before start of NH4+ or saline infusion. Cerebral blood flow (CBF) was monitored by a laser Doppler probe in brain cortex. ICP was monitored by placement of a catheter in the cerebrospinal fluid. CBF and ICP increased in PCA rats receiving NH4+ infusion compared to PCA controls and to all groups of sham-operated animals (P <.05). In the group of PCA rats pre-treated with tacrolimus before receiving ammonia infusion, the increase in ICP was ameliorated compared to the ammonia infused group receiving vehicle (P <.03). Tacrolimus also prevented an increase in CBF in the PCA group receiving NH4+ (P <.05) compared to the control groups. In conclusion, Tacrolimus prevents cerebral vasodilatation and ameliorates intracranial hypertension in PCA rats receiving NH4+ infusion. These findings indicate that tacrolimus could be of clinical value in the prevention of cerebral hyperemia, high ICP, and serious brain damage in patients with FHF.
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PMID:Tacrolimus ameliorates cerebral vasodilatation and intracranial hypertension in the rat with portacaval anastomosis and hyperammonemia. 1523 79

Brain edema with intracranial hypertension is a major complication in patients with acute liver failure. Current therapies for this complication include a variety of pharmacologic and interventional measures, some of which are frequently associated with adverse effects or contraindications. Even though these measures usually allow the control of intracranial hypertension for a certain period of time, recurrence is common. New therapies are therefore needed. Increasing clinical and experimental evidence suggests that induction of mild hypothermia (32 degrees C-35 degrees C) may be a therapeutic alternative. Similar to traumatic brain injury or brain stroke, induction of mild hypothermia seems highly effective to reduce intracranial pressure in patients with acute liver failure. Several mechanisms by which mild hypothermia may prevent brain edema and intracranial hypertension in this condition have been disclosed and may include beneficial effects on ammonia metabolism, as well as on the disturbances of brain osmolarity, cerebrovascular hemodynamics, brain glucose metabolism, inflammation, and others. Improvement of systemic hemodynamics and amelioration of liver injury may be other benefits of the systemic induction of mild hypothermia, but the impact of potential adverse events, such as infection, should also be taken into account. At a time when mild hypothermia is increasingly used in several specialized centers, performance of a randomized controlled trial seems critical to confirm the benefits of mild hypothermia in acute liver failure and to provide adequate guidelines for its use.
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PMID:Mild hypothermia for acute liver failure: a review of mechanisms of action. 1575 51

L-arginine is a basic endogenous amino acid. Its significant metabolic role as the product of ammonia detoxification, the urea cycle metabolite, the precursor of proteins, ornithine, urea and creatinine, and the amino acid involved in the formation of active enzyme centers was very well established. The current interest in this amino acid refers mainly to its close relation with an important signal molecule nitric oxide (NO). Literature review demonstrates that L-arginine, the only substrate of the NO production, affects cardiovascular system (blood vessels and heart). The majority of experimental and clinical studies clearly show a beneficial effect of L-arginine on endothelium in conditions associated with its hypofunction and thus with reduced NO synthesis. Some clinical studies involving healthy volunteers or patients suffering from hypertension and diabetes indicate that it may also regulate vascular hemostasis. Moreover, experiments performed on animals and in vitro data also suggest that L-arginine may have a complex antiaggregatory, anticoagulatory and profibrinolytic effect. Therefore, a novel therapeutic potential of L-arginine should be taken into consideration.
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PMID:L-arginine and cardiovascular system. 1584 73

In acute liver failure (ALF) patients that have raised increased intracranial pressure (ICP), mortality remains unacceptably high. There has been an explosion in the knowledge about the pathophysiological basis of raised ICP but treatment modalities are limited. Current therapy is aimed at reducing the circulating ammonia levels and attempts to reduce brain swelling which are only moderately effective. More recently, cerebral hyperemia has been suggested as being of major importance in the pathogenesis of increased ICP providing a new look at interventions such as hyperventilation, N-acetylcysteine, thiopentone sodium and propofol. More recently studies have focused upon the role of systemic inflammatory response in the pathogenesis of increased ICP and support the use of antibiotics prophylactically. The application of moderate hypothermia to treat uncontrolled intracranial hypertension seems promising and its exact place will be decided in a large trial being planned in USA and Europe. Early data from studies in an animal model suggests that albumin dialysis is a promising new tool to treat intracranial hypertension in patients with ALF. The recent advance in our understanding of the pathophysiological basis of intracranial hypertension has provided the platform for the discovery of new treatments.
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PMID:Pathophysiological basis of therapy of raised intracranial pressure in acute liver failure. 1592 6

In this prospective study of patients with fulminant hepatic failure (FHF), we tested the hypothesis that arterial hyperammonemia results in cerebral accumulation of the osmotic active amino acids glutamine and alanine, processes that were expected to correlate with intracranial pressure (ICP). By using in vivo brain microdialysis technique together with ICP monitoring in 17 FHF patients (10 females/7 males; median age 49 (range 18 to 66) years), we found that arterial ammonia concentration correlated to brain content of glutamine (r=0.47; P<0.05) but not to alanine. A persisting high arterial ammonia concentration (above 200 micromol/L) characterized patients who developed high ICP (n=8) while patients who did not experience surges of increased ICP (n=9) had a decline in the ammonia level (P<0.05). Moreover, brain glutamine and alanine concentrations were higher at baseline and increased further in patients who developed intracranial hypertension compared with patients who experienced no surges of high ICP. Brain glutamine concentration increased 32% from baseline to 6536 (697 to 9712) micromol/L (P<0.05), and alanine 44% from baseline to 104 (81 to 381) micromol/L (P<0.05). Brain concentration of glutamine (r=0.59, P<0.05), but not alanine, correlated to ICP. Also arterial ammonia concentration correlated to ICP (r=0.73, P<0.01). To conclude, this study shows that persistence of arterial hyperammonemia is associated with profound changes in the cerebral concentration of glutamine and alanine. The elevation of brain glutamine concentration correlated to ICP in patients with FHF.
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PMID:Persistent arterial hyperammonemia increases the concentration of glutamine and alanine in the brain and correlates with intracranial pressure in patients with fulminant hepatic failure. 1595 60

Hepatic encephalopathy (HE) is a neuropsychiatric syndrome associated with both acute and chronic liver dysfunction. It defines prognosis in acute liver injury in which patients can succumb with brain oedema and intracranial hypertension. In cirrhosis, it occurs insidiously, causing a range of neuropsychiatric disturbances. For over a century, we have known that ammonia is important in its pathogenesis and astrocytes are the cells that have been most commonly found to be affected neuropathologically. In this review we centre on the story of the 'sick astrocyte', focusing on the molecular pathogenesis of HE and the important role that inflammation has on its modulation. We describe new developments in this area with respect to potential targets for future therapies.
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PMID:The pathophysiologic basis of hepatic encephalopathy: central role for ammonia and inflammation. 1615 92

Encephalopathy, brain edema and intracranial hypertension are neurological complications responsible for substantial morbidity/mortality in patients with acute liver failure (ALF), where, aside from liver transplantation, there is currently a paucity of effective therapies. Mirroring its cerebro-protective effects in other clinical conditions, the induction of mild hypothermia may provide a potential therapeutic approach to the management of ALF. A solid mechanistic rationale for the use of mild hypothermia is provided by clinical and experimental studies showing its beneficial effects in relation to many of the key factors that determine the development of brain edema and intracranial hypertension in ALF, namely the delivery of ammonia to the brain, the disturbances of brain organic osmolytes and brain extracellular amino acids, cerebro-vascular haemodynamics, brain glucose metabolism, inflammation, subclinical seizure activity and alterations of gene expression. Initial uncontrolled clinical studies of mild hypothermia in patients with ALF suggest that it is an effective, feasible and safe approach. Randomized controlled clinical trials are now needed to adequately assess its efficacy, safety, clinical impact on global outcomes and to provide the guidelines for its use in ALF.
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PMID:Keeping cool in acute liver failure: rationale for the use of mild hypothermia. 1624 52


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